Tyvaso is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).

The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration [see Clinical Studies (14)].

Tyvaso is indicated for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%) [see Clinical Studies (14)].

Tyvaso is intended for oral inhalation using the Tyvaso Inhalation System, which consists of an ultrasonic, pulsed delivery device and its accessories.

Tyvaso is dosed in 4 separate, equally spaced treatment sessions per day, during waking hours. Each treatment session will take 2 to 3 minutes. The treatment sessions should be approximately 4 hours apart.

Initial Dosage:

Therapy should begin with 3 breaths of Tyvaso (18 mcg of treprostinil) per treatment session 4 times daily. If 3 breaths are not tolerated, reduce to 1 or 2 breaths and subsequently increase to 3 breaths, as tolerated.

Maintenance Dosage:

Dosage should be increased by an additional 3 breaths per treatment session, 4 times daily at approximately 1- to 2-week intervals. Studies establishing effectiveness in patients with PAH and PH-ILD have used target doses of 9 to 12 breaths per treatment session, 4 times daily. If adverse effects preclude titration to target dose, Tyvaso should be continued at the highest tolerated dose.

If a scheduled treatment session is missed or interrupted, therapy should be resumed as soon as possible at the usual dose.

Tyvaso must be used only with the Tyvaso Inhalation System. Patients should follow the instructions for use for operation of the Tyvaso Inhalation System and for daily cleaning of the device components after the last treatment session of the day. To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up Tyvaso Inhalation System device.

Do not mix Tyvaso with other medications in the Tyvaso Inhalation System. Compatibility of Tyvaso with other medications has not been studied.

The Tyvaso Inhalation System should be prepared for use each day according to the instructions for use. One ampule of Tyvaso contains a sufficient volume of medication for all 4 treatment sessions in a single day. Prior to the first treatment session, the patient should twist the top off a single Tyvaso ampule and squeeze the entire contents into the medicine cup. Between each of the 4 daily treatment sessions, the device should be capped and stored upright with the remaining medication inside.

At the end of each day, the medicine cup and any remaining medication must be discarded. The device must be cleaned each day according to the instructions for use.

Avoid skin or eye contact with Tyvaso solution. Do not orally ingest the Tyvaso solution.

Sterile solution for oral inhalation: 2.9 mL ampule containing 1.74 mg of treprostinil (0.6 mg per mL).

{ "type": "p", "children": [], "text": "Sterile solution for oral inhalation: 2.9 mL ampule containing 1.74 mg of treprostinil (0.6 mg per mL)." }

None.

{ "type": "p", "children": [], "text": "None." }

Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Tyvaso may produce symptomatic hypotension.

Tyvaso inhibits platelet aggregation and increases the risk of bleeding.

Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

Like other inhaled prostaglandins, Tyvaso may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with Tyvaso Inhalation Solution.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pulmonary Arterial Hypertension

In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most commonly reported adverse reactions on Tyvaso included cough and throat irritation, headache, gastrointestinal effects, muscle, jaw or bone pain, dizziness, flushing, and syncope. Table 1 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with Tyvaso than with placebo.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1: Adverse Events in ≥4% of PAH Patients Receiving Tyvaso and More Frequent<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> than Placebo in TRIUMPH I</span> </caption> <col align="center" valign="middle" width="50%"/> <col align="center" valign="middle" width="25%"/> <col align="center" valign="middle" width="25%"/> <thead> <tr class="First"> <th align="center" class="Lrule Rrule" rowspan="2">Adverse Event</th><th align="center" class="Botrule Rrule" colspan="2">Treatment<br/> n (%)</th> </tr> <tr class="Last"> <th align="center" class="Rrule">Tyvaso<br/>n=115</th><th align="center" class="Rrule">Placebo<br/>n=120</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>More than 3% greater than placebo</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Cough</td><td align="center" class="Rrule">62 (54)</td><td align="center" class="Rrule">35 (29)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">47 (41)</td><td align="center" class="Rrule">27 (23)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Throat Irritation / Pharyngolaryngeal Pain</td><td align="center" class="Rrule">29 (25)</td><td align="center" class="Rrule">17 (14)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">22 (19)</td><td align="center" class="Rrule">13 (11)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Flushing</td><td align="center" class="Rrule">17 (15)</td><td align="center" class="Rrule">1 (&lt;1)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Syncope</td><td align="center" class="Rrule">7 (6)</td><td align="center" class="Rrule">1 (&lt;1)</td> </tr> </tbody> </table></div>

The safety of Tyvaso was also studied in a long-term, open-label extension study in which 206 patients were dosed for a mean duration of 2.3 years, with a maximum exposure of 5.4 years. Eighty-nine percent (89%) of patients achieved the target dose of 9 breaths, 4 times daily. Forty-two percent (42%) achieved a dose of 12 breaths, 4 times daily. The adverse events during this chronic dosing study were qualitatively similar to those observed in the 12-week placebo-controlled trial.

In a prospective, observational study comparing patients taking Tyvaso (958 patient-years of exposure) and a control group (treatment with other approved therapies for PAH; 1094 patient-years), Tyvaso was associated with a higher rate of cough (16.2 vs. 10.9 per 100 patient-years), throat irritation (4.5 vs. 1.2 per 100 pt-years), nasal discomfort (2.6 vs. 1.3 per 100 pt-years), and hemoptysis (2.5 vs. 1.3 per 100 pt-years) compared to the control group.

Pulmonary Hypertension Associated with ILD

In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions were similar to the experience in studies of PAH.

The adverse reaction of angioedema has been identified during the post-approval use of Tyvaso. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure.

In a human pharmacokinetic study conducted with bosentan (250 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and bosentan were observed.

In a human pharmacokinetic study conducted with sildenafil (60 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and sildenafil were observed.

In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A. Additionally, treprostinil does not induce cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A.

Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8 [see Warnings and Precautions (5.3)].

Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively, in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S- warfarin and the international normalized ratio (INR) in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.

Risk Summary

Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, there are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations). In animal studies, no adverse reproductive and developmental effects were seen for treprostinil at ≥9 and ≥145 times the human exposure when based on Cmax and AUC, respectively, following a single treprostinil dose of 54 mcg.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and embryo-fetal risk

Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality.

Data

Animal reproduction studies have been conducted with treprostinil via continuous subcutaneous administration and with treprostinil diolamine administered orally. In studies with orally administered treprostinil diolamine, no adverse effect doses for fetal viability/growth, fetal development (teratogenicity), and postnatal development were determined in rats. In pregnant rats, no evidence of harm to the fetus was observed following oral administration of treprostinil diolamine at the highest dose tested (20 mg/kg/day), which represents about 154 and 1479 times the human exposure, when based on Cmax and AUC, respectively, following a single Tyvaso dose of 54 mcg. In pregnant rabbits, external fetal and soft tissue malformations and fetal skeletal malformation occurred. The dose at which no adverse effects were seen (0.5 mg/kg/day) represents about 9 and 145 times the human exposure, when based on Cmax and AUC, respectively, following a single Tyvaso dose of 54 mcg. No treprostinil treatment-related effects on labor and delivery were seen in animal studies. Animal reproduction studies are not always predictive of human response.

Risk Summary

There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.

Safety and effectiveness in pediatric patients have not been established. Clinical studies of Tyvaso did not include patients younger than 18 years to determine whether they respond differently from older patients.

Across clinical studies used to establish the effectiveness of Tyvaso in patients with PAH and PH-ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects with mild-to-moderate hepatic insufficiency. Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Clinical Pharmacology (12.3)].

No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis [see Clinical Pharmacology (12.3)].

In general, symptoms of overdose with Tyvaso include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved.

{ "type": "p", "children": [], "text": "In general, symptoms of overdose with Tyvaso include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved." }

Tyvaso is a sterile formulation of treprostinil, a prostacyclin mimetic, intended for administration by oral inhalation using the Tyvaso Inhalation System. Tyvaso is supplied in 2.9 mL low density polyethylene (LDPE) ampules, containing 1.74 mg treprostinil (0.6 mg/mL). Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.58 mg sodium hydroxide, 11.7 mg 1 N hydrochloric acid, and water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust pH between 6.0 and 7.2.

{ "type": "p", "children": [], "text": "Tyvaso is a sterile formulation of treprostinil, a prostacyclin mimetic, intended for administration by oral inhalation using the Tyvaso Inhalation System. Tyvaso is supplied in 2.9 mL low density polyethylene (LDPE) ampules, containing 1.74 mg treprostinil (0.6 mg/mL). Each ampule also contains 18.9 mg sodium chloride, 18.3 mg sodium citrate dihydrate, 0.58 mg sodium hydroxide, 11.7 mg 1 N hydrochloric acid, and water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust pH between 6.0 and 7.2." }

Treprostinil is (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C23H34O5.

{ "type": "p", "children": [], "text": "Treprostinil is (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C23H34O5." }

The structural formula of treprostinil is:

{ "type": "p", "children": [], "text": "The structural formula of treprostinil is:" }

Treprostinil is a prostacyclin analogue. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.

In a clinical trial of 240 healthy volunteers, single doses of Tyvaso 54 mcg (the target maintenance dose per session) and 84 mcg (supratherapeutic inhalation dose) prolonged the corrected QTc interval by approximately 10 ms. The QTc effect dissipated rapidly as the concentration of treprostinil decreased.

Pharmacokinetic information for single doses of inhaled treprostinil was obtained in healthy volunteers in 3 separate studies. Treprostinil systemic exposure (AUC and Cmax) post-inhalation was shown to be proportional to the doses administered (18 mcg to 90 mcg).

Absorption

In a 3-period crossover study, the bioavailability of 2 single doses of Tyvaso (18 mcg and 36 mcg) was compared with that of intravenous treprostinil in 18 healthy volunteers. Mean estimates of the absolute systemic bioavailability of treprostinil after inhalation were approximately 64% (18 mcg) and 72% (36 mcg).

Treprostinil plasma exposure data were obtained from 2 studies at the target maintenance dose, 54 mcg. The mean Cmax at the target dose was 0.91 and 1.32 ng/mL with corresponding mean Tmax of 0.25 and 0.12 hr, respectively. The mean AUC for the 54-mcg dose was 0.81 and 0.97 hr∙ng/mL, respectively.

Distribution

Following parenteral infusion, the apparent steady state volume of distribution (Vss) of treprostinil is approximately 14 L/70 kg ideal body weight.

In vitro treprostinil is 91% bound to human plasma proteins over the 330 to 10,000 mcg/L concentration range.

Metabolism and Excretion

Of subcutaneously administered treprostinil, only 4% is excreted unchanged in urine. Treprostinil is substantially metabolized by the liver, primarily by CYP2C8. Metabolites are excreted in urine (79%) and feces (13%) over 10 days. Five apparently inactive metabolites were detected in the urine, each accounting for 10 to 15% of the dose administered. Four of the metabolites are products of oxidation of the 3-hydroxyloctyl side chain and 1 is a glucuroconjugated derivative (treprostinil glucuronide).

The elimination of treprostinil (following subcutaneous administration of treprostinil) is biphasic, with a terminal elimination half-life of approximately 4 hours using a 2-compartment model.

Specific Populations

Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects presenting with mild-to-moderate hepatic insufficiency. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Use in Specific Populations (8.6)].

Renal Impairment

In patients with severe renal impairment requiring dialysis (n=8), administration of a single 1 mg dose of orally administered treprostinil pre- and post-dialysis resulted in AUC0-inf that was not significantly altered compared to healthy subjects [see Use in Specific Populations (8.7)].

A 2-year rat carcinogenicity study was performed with treprostinil inhalation at target doses of 5.26, 10.6, and 34.1 mcg/kg/day. There was no evidence for carcinogenic potential associated with treprostinil inhalation in rats at systemic exposure levels up to 35 times the clinical exposure at the target maintenance dose of 54 mcg. In vitro and in vivo genetic toxicology studies did not demonstrate any mutagenic or clastogenic effects of treprostinil. Treprostinil sodium did not affect fertility or mating performance of male or female rats given continuous subcutaneous infusions at rates of up to 450 ng treprostinil/kg/min. In this study, males were dosed from 10 weeks prior to mating and through the 2-week mating period. Females were dosed from 2 weeks prior to mating until gestational day 6.

Oral administration of treprostinil diolamine to Tg.rasH2 mice at 0, 5, 10, and 20 mg/kg/day in males and 0, 3, 7.5, and 15 mg/kg/day in females daily for 26 weeks did not significantly increase the incidence of tumors.

Treprostinil diolamine was tested in vivo in a rat micronucleus assay and did not induce an increased incidence of micronucleated polychromatic erythrocytes.

In a 2-year rat study with treprostinil inhalation at target doses of 5.26, 10.6, and 34.1 mcg/kg/day, there were more deaths (11) in the mid- and high-dose treprostinil groups during the first 9 weeks of the study, compared to 1 in control groups. At the high-dose level, males showed a higher incidence of inflammation in teeth and preputial gland, and females showed higher incidences of inflammation and urothelial hyperplasia in the urinary bladder. The exposures in rats at mid- and high-dose levels were about 15 and 35 times, respectively, the clinical exposure at the target maintenance dose of 54 mcg.

TRIUMPH I, was a 12-week, randomized, double-blind, placebo-controlled, multicenter study of patients with PAH. The study population included 235 clinically stable subjects with PAH (WHO Group 1), nearly all with NYHA Class III (98%) symptoms who were receiving either bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase-5 inhibitor) for at least 3 months prior to study initiation. Concomitant therapy also could have included anticoagulants, other vasodilators (e.g., calcium channel blockers), diuretics, oxygen, and digitalis, but not a prostacyclin. These patients were administered either placebo or Tyvaso in 4 daily treatment sessions with a target dose of 9 breaths (54 mcg) per session over the course of the 12-week study. Patients were predominately female (82%), had the origin of PAH as idiopathic/heritable (56%), secondary to connective tissue diseases (33%) or secondary to HIV or previous use of anorexigens (12%); bosentan was the concomitant oral medication in 70% of those enrolled, sildenafil in 30%.

The primary efficacy endpoint of the trial was the change in 6-Minute Walk Distance (6MWD) relative to baseline at 12 weeks. 6MWD was measured at peak exposure (between 10 and 60 minutes after dosing), and 3 to 5 hours after bosentan or 0.5 to 2 hours after sildenafil. Patients receiving Tyvaso had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12 (p<0.001). The distribution of these 6MWD changes from baseline at Week 12 were plotted across the range of observed values (Figure 1). 6MWD measured at trough exposure (defined as measurement of 6MWD at least 4 hours after dosing) improved by 14 meters. There were no placebo-controlled 6MWD assessments made after 12 weeks.

Figure 1: Distributions of 6MWD Changes from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso

The placebo-corrected median treatment effect on 6MWD was estimated (using the Hodges-Lehmann estimator) within various subpopulations defined by age quartile, gender, geographic region of the study site, disease etiology, baseline 6MWD quartile, and type of background therapy (Figure 2).

Figure 2: Placebo-Corrected Median Treatment Effect (Hodges-Lehmann Estimate with 95% CI) on 6MWD Change from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso for Various Subgroups

In long-term follow-up of patients who were treated with Tyvaso in the pivotal study and the open-label extension (N=206), Kaplan-Meier estimates of survival at 1, 2, and 3 years were 97%, 91%, and 82%, respectively. These uncontrolled observations do not allow comparison with a control group not given Tyvaso and cannot be used to determine the long-term effect of Tyvaso on mortality.

INCREASE was a 16-week, randomized, double-blind, placebo-controlled, multicenter study that enrolled 326 patients with PH-ILD. Enrolled study patients predominately had etiologies of idiopathic interstitial pneumonia (45%) inclusive of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema (25%), and WHO Group 3 connective tissue disease (22%). The mean baseline 6MWD was 260 meters.

Patients in the INCREASE study were randomized (1:1) to either placebo or Tyvaso in 4 daily treatment sessions with a target dose of 9 breaths (54 mcg) per session and a maximum dose of 12 breaths (72 mcg) per session over the course of the 16-week study. Approximately 75% of patients randomized to Tyvaso titrated up to a dose of 9 breaths, 4 times daily or greater, with 48% of patients randomized to Tyvaso reaching a dose of 12 breaths, 4 times daily during the study.

The primary efficacy endpoint was the change in 6MWD measured at peak exposure (between 10 and 60 minutes after dosing) from baseline to Week 16. Patients receiving Tyvaso had a placebo-corrected median change from baseline in peak 6MWD of 21 meters at Week 16 (p=0.004) using Hodges-Lehmann estimate (Figure 3).

Figure 3: Hodges-Lehmann Estimate of Treatment Effect by Visit for 6MWD at Peak Exposure (PH-ILD)

The treatment effect on 6MWD at Week 16 was consistent for various subgroups, including etiology of PH-ILD, disease severity, age, sex, baseline hemodynamics, and dose (Figure 4).

Figure 4: Forest Plot on Subgroup Analyses of Peak 6MWD (Meter) at Week 16 (PH-ILD)

Time to clinical worsening in the INCREASE study was defined as the time of randomization until 1 of the following criteria were met: hospitalization due to a cardiopulmonary indication, decrease in 6MWD >15% from baseline directly related to PH-ILD at 2 consecutive visits and at least 24 hours apart, death (all causes), or lung transplantation. Treatment with Tyvaso in patients with PH-ILD resulted in numerically fewer hospitalizations. The numbers of reported deaths were the same for both treatment groups (Table 2). Overall, treatment with Tyvaso demonstrated a statistically significant increase in the time to first clinical worsening event (log-rank test p=0.041; Figure 5), and a 39% overall reduction in the risk of a clinical worsening event (HR=0.61 [95% CI; 0.40, 0.92]; Figure 5).

<div class="scrollingtable"><table width="80%"> <caption> <span>Table 2: Clinical Worsening Events (PH-ILD)</span> </caption> <col align="center" valign="top" width="12%"/> <col align="left" valign="top" width="24%"/> <col align="center" valign="top" width="21%"/> <col align="center" valign="top" width="21%"/> <col align="center" valign="top" width="22%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" colspan="2"></th><th align="center" class="Rrule">Tyvaso<br/>n=163<br/>n (%)</th><th align="center" class="Rrule">Placebo <br/>n=163<br/>n (%)</th><th align="center" class="Rrule">HR (95% CI)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Clinical worsening</span></td><td align="center" class="Rrule">37 (22.7%)</td><td align="center" class="Rrule">54 (33.1%)</td><td align="center" class="Rrule">0.61 (0.40, 0.92)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" rowspan="4" valign="middle"><span class="Bold">First contributing event</span></td><td align="left" class="Rrule"><span class="Bold">Hospitalization due to a cardiopulmonary indication</span></td><td align="center" class="Rrule">18 (11.0%)</td><td align="center" class="Rrule">24 (14.7%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Decrease in 6MWD &gt;15% from baseline directly related to PH-ILD</span></td><td align="center" class="Rrule">13 (8.0%)</td><td align="center" class="Rrule">26 (16.0%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Death (all causes)</span></td><td align="center" class="Rrule">4 (2.5%)</td><td align="center" class="Rrule">4 (2.5%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Lung transplantation</span></td><td align="center" class="Rrule">2 (1.2%)</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" rowspan="4" valign="middle"><span class="Bold">First of each event</span></td><td align="left" class="Rrule"><span class="Bold">Hospitalization due to a cardiopulmonary indication</span></td><td align="center" class="Rrule">21 (12.9%)</td><td align="center" class="Rrule">30 (18.4%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Decrease in 6MWD &gt;15% from baseline directly related to PH-ILD</span></td><td align="center" class="Rrule">16 (9.8%)</td><td align="center" class="Rrule">31 (19.0%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Death (all causes)</span></td><td align="center" class="Rrule">8 (4.9%)</td><td align="center" class="Rrule">10 (6.1%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Last"> <td align="left" class="Rrule"><span class="Bold">Lung transplantation</span></td><td align="center" class="Rrule">2 (1.2%)</td><td align="center" class="Rrule">1 (0.6%)</td><td align="center" class="Rrule"></td> </tr> </tbody> </table></div>

Figure 5: Kaplan-Meier Plot of Time to Clinical Worsening Events (PH-ILD)

Ampules of Tyvaso are stable until the date indicated when stored in the unopened foil pouch at 20-25°C (68-77°F) with excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Once the foil pack is opened, ampules should be used within 7 days. Because Tyvaso is light-sensitive, unopened ampules should be stored in the foil pouch.

One ampule of Tyvaso should be used each day in the Tyvaso Inhalation System. After a Tyvaso ampule is opened and transferred to the medicine cup, the solution should remain in the device for no more than 1 day (24 hours). Any remaining solution should be discarded at the end of the day.

Tyvaso Inhalation System Starter Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-01)

Tyvaso Inhalation System Refill Kit containing a 28-ampule carton of Tyvaso (7 foil pouches each containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and accessories. (NDC 66302-206-02)

Tyvaso 4 Pack Carton with 1 foil pouch containing four 2.9 mL ampules. Each ampule contains 1.74 mg treprostinil (0.6 mg per mL). (NDC 66302-206-03)

Tyvaso Inhalation System Institutional Starter Kit containing a 4-ampule carton of Tyvaso (1 foil pouch containing four 2.9 mL ampules; each ampule contains 1.74 mg treprostinil [0.6 mg per mL]) and the Tyvaso Inhalation System. (NDC 66302-206-04)

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Instructions for Use)." }

Train patients in the administration process for Tyvaso, including dosing, Tyvaso Inhalation System set up, operation, cleaning, and maintenance, according to the instructions for use [see Dosage and Administration (2.1, 2.2)].

{ "type": "p", "children": [], "text": "Train patients in the administration process for Tyvaso, including dosing, Tyvaso Inhalation System set up, operation, cleaning, and maintenance, according to the instructions for use [see Dosage and Administration (2.1, 2.2)]." }

To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up Tyvaso Inhalation System device [see Dosage and Administration (2.2)].

{ "type": "p", "children": [], "text": "To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up Tyvaso Inhalation System device [see Dosage and Administration (2.2)]." }

In the event that a scheduled treatment session is missed or interrupted, resume therapy as soon as possible [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "In the event that a scheduled treatment session is missed or interrupted, resume therapy as soon as possible [see Dosage and Administration (2.1)]." }

If Tyvaso comes in contact with the skin or eyes, instruct patients to rinse immediately with water [see Dosage and Administration (2.2)].

{ "type": "p", "children": [], "text": "If Tyvaso comes in contact with the skin or eyes, instruct patients to rinse immediately with water [see Dosage and Administration (2.2)]." }

©Copyright 2022 United Therapeutics Corp. All rights reserved.

{ "type": "p", "children": [], "text": "\n©Copyright 2022 United Therapeutics Corp. All rights reserved." }

Tyvaso manufactured for:

{ "type": "p", "children": [], "text": "Tyvaso manufactured for:" }

United Therapeutics Corp.Research Triangle Park, NC 27709

{ "type": "p", "children": [], "text": "United Therapeutics Corp.Research Triangle Park, NC 27709" }

TYVASO® INHALATION SYSTEM Instructions for Use

{ "type": "p", "children": [], "text": "\nTYVASO®\n\nINHALATION SYSTEM\n\nInstructions for Use\n" }

TYVASO® (treprostinil) INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "\nTYVASO®\n\n(treprostinil)\n\nINHALATIONSOLUTION\n" }

Table of Contents

{ "type": "p", "children": [], "text": "\nTable of Contents\n" }

<div class="scrollingtable"><table class="Noautorules" width="60%"> <col align="left" valign="bottom" width="95%"/> <col align="right" valign="bottom" width="5%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">General Instructions</span></td><td align="right"><span class="Bold">2</span></td> </tr> <tr> <td align="left"><span class="Bold">Introduction</span></td><td align="right"><span class="Bold">3</span></td> </tr> <tr> <td align="left"><span class="Bold">Preparing for Treatment With TYVASO</span></td><td align="right"><span class="Bold">3</span></td> </tr> <tr> <td align="left">  Preparing the Use Environment for Treatment</td><td align="right">3</td> </tr> <tr> <td align="left">  Markings, Indicators, and Symbols</td><td align="right">4</td> </tr> <tr> <td align="left">  Gathering Supplies</td><td align="right">6</td> </tr> <tr> <td align="left"><span class="Bold">Setting Up Your TYVASO Inhalation System</span></td><td align="right"><span class="Bold">8</span></td> </tr> <tr> <td align="left">  Filling the Inhalation Device Chamber and Medicine Cup</td><td align="right">8</td> </tr> <tr> <td align="left">  Assembling the Inhalation Device</td><td align="right">10</td> </tr> <tr> <td align="left">  Turning On the Inhalation Device</td><td align="right">13</td> </tr> <tr> <td align="left"><span class="Bold">Setting the Number of Breaths in a Treatment Session</span></td><td align="right"><span class="Bold">14</span></td> </tr> <tr> <td align="left"><span class="Bold">Inhaling Your Medicine (TYVASO)</span></td><td align="right"><span class="Bold">16</span></td> </tr> <tr> <td align="left"><span class="Bold">Storing the TYVASO Inhalation System Between Treatment Sessions</span></td><td align="right"><span class="Bold">20</span></td> </tr> <tr> <td align="left"><span class="Bold">Cleaning and Maintenance of the TYVASO Inhalation System</span></td><td align="right"><span class="Bold">24</span></td> </tr> <tr> <td align="left">  End of Day Cleaning of the Accessories</td><td align="right">24</td> </tr> <tr> <td align="left">  Weekly Cleaning</td><td align="right">27</td> </tr> <tr> <td align="left">  Monthly Refill Kit</td><td align="right">27</td> </tr> <tr> <td align="left">  Device Replacement</td><td align="right">27</td> </tr> <tr> <td align="left"><span class="Bold">Charging Your TYVASO Inhalation System</span></td><td align="right"><span class="Bold">28</span></td> </tr> <tr> <td align="left">  Rechargeable Battery</td><td align="right">28</td> </tr> <tr> <td align="left"><span class="Bold">Troubleshooting the TYVASO Inhalation System</span></td><td align="right"><span class="Bold">30</span></td> </tr> <tr> <td align="left"><span class="Bold">Specifications</span></td><td align="right"><span class="Bold">36</span></td> </tr> <tr> <td align="left"><span class="Bold">Glossary</span></td><td align="right"><span class="Bold">38</span></td> </tr> <tr> <td align="left"><span class="Bold">Warranty Information</span></td><td align="right"><span class="Bold">40</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"60%\">\n<col align=\"left\" valign=\"bottom\" width=\"95%\"/>\n<col align=\"right\" valign=\"bottom\" width=\"5%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">General Instructions</span></td><td align=\"right\"><span class=\"Bold\">2</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Introduction</span></td><td align=\"right\"><span class=\"Bold\">3</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Preparing for Treatment With TYVASO</span></td><td align=\"right\"><span class=\"Bold\">3</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Preparing the Use Environment for Treatment</td><td align=\"right\">3</td>\n</tr>\n<tr>\n<td align=\"left\">  Markings, Indicators, and Symbols</td><td align=\"right\">4</td>\n</tr>\n<tr>\n<td align=\"left\">  Gathering Supplies</td><td align=\"right\">6</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Setting Up Your TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">8</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Filling the Inhalation Device Chamber and Medicine Cup</td><td align=\"right\">8</td>\n</tr>\n<tr>\n<td align=\"left\">  Assembling the Inhalation Device</td><td align=\"right\">10</td>\n</tr>\n<tr>\n<td align=\"left\">  Turning On the Inhalation Device</td><td align=\"right\">13</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Setting the Number of Breaths in a Treatment Session</span></td><td align=\"right\"><span class=\"Bold\">14</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Inhaling Your Medicine (TYVASO)</span></td><td align=\"right\"><span class=\"Bold\">16</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Storing the TYVASO Inhalation System Between Treatment Sessions</span></td><td align=\"right\"><span class=\"Bold\">20</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Cleaning and Maintenance of the TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">24</span></td>\n</tr>\n<tr>\n<td align=\"left\">  End of Day Cleaning of the Accessories</td><td align=\"right\">24</td>\n</tr>\n<tr>\n<td align=\"left\">  Weekly Cleaning</td><td align=\"right\">27</td>\n</tr>\n<tr>\n<td align=\"left\">  Monthly Refill Kit</td><td align=\"right\">27</td>\n</tr>\n<tr>\n<td align=\"left\">  Device Replacement</td><td align=\"right\">27</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Charging Your TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">28</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Rechargeable Battery</td><td align=\"right\">28</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Troubleshooting the TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">30</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Specifications</span></td><td align=\"right\"><span class=\"Bold\">36</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Glossary</span></td><td align=\"right\"><span class=\"Bold\">38</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Warranty Information</span></td><td align=\"right\"><span class=\"Bold\">40</span></td>\n</tr>\n</tbody>\n</table></div>" }

General Instructions

{ "type": "p", "children": [], "text": "\nGeneral Instructions\n" }

The TYVASO Inhalation System should be handled with care.

{ "type": "p", "children": [], "text": "The TYVASO Inhalation System should be handled with care." }

Follow these important instructions to ensure proper use:

{ "type": "p", "children": [], "text": "Follow these important instructions to ensure proper use:" }

{ "type": "ul", "children": [ "Always unplug the device after each use.", "Do not immerse the device in water or other liquids.", "Do not place the device in a microwave or regular oven.", "Do not place the device or use the device in the presence of strong electric or magnetic fields (eg, microwave oven, magnetic imaging equipment).", "Do not leave the device alone with a small child.", "Do not use the device near flammable liquids and materials or heated surfaces.", "Read the instructions carefully and completely to prevent damage to your TYVASO Inhalation System and help you get the best results.", "This device should only be used on the order of your doctor or licensed healthcare practitioner.", "Ensure the breath counter is correctly programmed prior to beginning a treatment (see page 14).", "Do not peel or remove the labels from device.", "Do not drop the device." ], "text": "" }

Introduction

{ "type": "p", "children": [], "text": "\nIntroduction\n" }

Your doctor has prescribed TYVASO® (treprostinil) Inhalation Solution. Please see the accompanying Patient Package Insert for important safety information on TYVASO.

{ "type": "p", "children": [], "text": "Your doctor has prescribed TYVASO® (treprostinil) Inhalation Solution. Please see the accompanying Patient Package Insert for important safety information on TYVASO." }

TYVASO is breathed in (inhaled) using the TYVASO Inhalation System, which consists of the inhalation device and its accessories.

{ "type": "p", "children": [], "text": "TYVASO is breathed in (inhaled) using the TYVASO Inhalation System, which consists of the inhalation device and its accessories." }

These Instructions for Use (IFU) for the TYVASO Inhalation System provide important safety information. It is important that you read these instructions and the TYVASO Patient Package Insert (PPI) before setting up and using the TYVASO Inhalation System. If you have any questions, talk to your doctor or specialty pharmacy provider.

{ "type": "p", "children": [], "text": "These Instructions for Use (IFU) for the TYVASO Inhalation System provide important safety information. It is important that you read these instructions and the TYVASO Patient Package Insert (PPI) before setting up and using the TYVASO Inhalation System. If you have any questions, talk to your doctor or specialty pharmacy provider." }

Before beginning treatment with TYVASO, you will receive either a Patient Starter Kit containing a 28-day supply of TYVASO or an Institutional Starter Kit containing a 4-day supply of medication. Both kits include two (2) complete inhalation devices (all accessories and supplies included). When you refill your prescription for TYVASO each month, you will receive a Refill Kit that contains a 28-day supply of TYVASO and new accessories. You will receive a replacement device every two (2) years.

{ "type": "p", "children": [], "text": "Before beginning treatment with TYVASO, you will receive either a Patient Starter Kit containing a 28-day supply of TYVASO or an Institutional Starter Kit containing a 4-day supply of medication. Both kits include two (2) complete inhalation devices (all accessories and supplies included). When you refill your prescription for TYVASO each month, you will receive a Refill Kit that contains a 28-day supply of TYVASO and new accessories. You will receive a replacement device every two (2) years." }

Preparing for Treatment With TYVASO

{ "type": "p", "children": [], "text": "\nPreparing for Treatment With TYVASO\n" }

Preparing the Use Environment for Treatment

{ "type": "p", "children": [], "text": "\nPreparing the Use Environment for Treatment\n" }

Follow these important instructions before setting up your treatment:

{ "type": "p", "children": [], "text": "Follow these important instructions before setting up your treatment:" }

{ "type": "ul", "children": [ "Use the device in a quiet, distraction-free area.", "Try to use the device at times when your treatment will not be interrupted. If you encounter any distractions during treatment, you can pause your treatment (see page 19).", "Use the device in a comfortable space where you can stand or sit in an upright position that allows you to take deep breaths.", "Use the device in an area that provides enough space for the TYVASO Inhalation System and its accessories.", "Gather all necessary supplies before starting to prepare for treatment (see pages 6 and 7).", "The TYVASO Inhalation System is recommended for use indoors. Be sure to use and store the inhalation device in environments that match the specified temperature and humidity ranges (see Specifications on page 36)." ], "text": "" }

Markings, Indicators, and Symbols

{ "type": "p", "children": [], "text": "\nMarkings, Indicators, and Symbols\n" }

Device markings

{ "type": "p", "children": [], "text": "\nDevice markings\n" }

<div class="scrollingtable"><table width="100%"> <col align="center" valign="middle" width="15%"/> <col align="left" valign="middle" width="85%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-06.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System complies with the requirements of Protection Class II. Class II equipment provides additional precautions, over and above basic insulation, to provide protection against electric shock.</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-07.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Please read the accompanying instructions and labels for important information regarding the TYVASO Inhalation System.</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-08.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System has a Type B Applied part. Type B Applied parts comply with specific requirements to provide protection against shock and are not suitable for direct cardiac applications.</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-09.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System should only be used on the order of your doctor or licensed healthcare provider.</td> </tr> <tr class="Last"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-10.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System requires a 12V DC power supply.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"center\" valign=\"middle\" width=\"15%\"/>\n<col align=\"left\" valign=\"middle\" width=\"85%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-06.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System complies with the requirements of Protection Class II. Class II equipment provides additional precautions, over and above basic insulation, to provide protection against electric shock.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-07.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Please read the accompanying instructions and labels for important information regarding the TYVASO Inhalation System.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-08.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System has a Type B Applied part. Type B Applied parts comply with specific requirements to provide protection against shock and are not suitable for direct cardiac applications.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-09.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System should only be used on the order of your doctor or licensed healthcare provider.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-10.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System requires a 12V DC power supply.</td>\n</tr>\n</tbody>\n</table></div>" }

Gathering Supplies

{ "type": "p", "children": [], "text": "\nGathering Supplies\n" }

Gather the following supplies before starting treatment. Use only the parts and accessories that are provided with your starter kit or in the monthly refill kit. Note: supplies are not shown to scale.

{ "type": "p", "children": [], "text": "Gather the following supplies before starting treatment. Use only the parts and accessories that are provided with your starter kit or in the monthly refill kit. Note: supplies are not shown to scale." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="40%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="30%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">1. Inhalation device</span></td><td align="left"><span class="Bold">2. Water Level Cup with 45 mL of distilled water</span></td><td align="left"><span class="Bold">3. Pack of TYVASO ampules</span></td> </tr> <tr> <td align="left" rowspan="4"> <p class="First"> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-11.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></p> </td><td align="left"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-12.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-13.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="left">Use only distilled water to fill your inhalation device once per day.</td><td align="center">Use one (1) ampule per day.</td> </tr> <tr> <td align="left" colspan="2"><span class="Bold">4. One of the provided power sources</span></td> </tr> <tr> <td align="left" colspan="2"> <p class="First"> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-14.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">1. Inhalation device</span></td><td align=\"left\"><span class=\"Bold\">2. Water Level Cup with 45 mL of distilled water</span></td><td align=\"left\"><span class=\"Bold\">3. Pack of TYVASO ampules</span></td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"4\">\n<p class=\"First\">\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-11.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></p>\n</td><td align=\"left\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-12.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-13.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"left\">Use only distilled water to fill your inhalation device once per day.</td><td align=\"center\">Use one (1) ampule per day.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\"><span class=\"Bold\">4. One of the provided power sources</span></td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">\n<p class=\"First\">\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-14.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <tfoot> <tr> <td align="left" colspan="5" valign="top">Note: Supplies are not shown to scale.</td> </tr> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-2" name="footnote-2">*</a> </dt> <dd>These accessories are replaced every month. Replacement accessories are included in the Monthly Refill Kit.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="left" colspan="5"><span class="Bold">5. Accessories</span></td> </tr> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-15.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-16.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-17.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-18.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-19.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Medicine cups<a class="Sup" href="#footnote-2" name="footnote-reference-2">*</a></td><td align="center">Dome assembly with baffle plate inside<a class="Sup" href="#footnote-2">*</a></td><td align="center">Inhalation piece<a class="Sup" href="#footnote-2">*</a></td><td align="center">Mouthpiece<a class="Sup" href="#footnote-2">*</a></td><td align="center">Two (2) Filter shells<a class="Sup" href="#footnote-2">*</a></td> </tr> <tr> <td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-20.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-21.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-22.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-23.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-24.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Filter membranes (use two (2) per day)<a class="Sup" href="#footnote-2">*</a></td><td align="center">Plugs<a class="Sup" href="#footnote-2">*</a></td><td align="center">Treatment Tracker<a class="Sup" href="#footnote-2">*</a></td><td align="center">Carrying case</td><td align="center">Distilled water carrier (optional)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<col align=\"center\" valign=\"top\" width=\"20%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"5\" valign=\"top\">Note: Supplies are not shown to scale.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"5\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-2\" name=\"footnote-2\">*</a>\n</dt>\n<dd>These accessories are replaced every month. Replacement accessories are included in the Monthly Refill Kit.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" colspan=\"5\"><span class=\"Bold\">5. Accessories</span></td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-15.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-16.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-17.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-18.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-19.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Medicine cups<a class=\"Sup\" href=\"#footnote-2\" name=\"footnote-reference-2\">*</a></td><td align=\"center\">Dome assembly with baffle plate inside<a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\">Inhalation piece<a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\">Mouthpiece<a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\">Two (2) Filter shells<a class=\"Sup\" href=\"#footnote-2\">*</a></td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-20.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-21.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-22.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-23.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-24.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Filter membranes (use two (2) per day)<a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\">Plugs<a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\">Treatment Tracker<a class=\"Sup\" href=\"#footnote-2\">*</a></td><td align=\"center\">Carrying case</td><td align=\"center\">Distilled water carrier (optional)</td>\n</tr>\n</tbody>\n</table></div>" }

Setting Up Your TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nSetting Up Your TYVASO Inhalation System\n" }

Filling the Inhalation Device Chamber and Medicine Cup

{ "type": "p", "children": [], "text": "\nFilling the Inhalation Device Chamber and Medicine Cup\n" }

Before using the TYVASO Inhalation System, you should:

{ "type": "p", "children": [], "text": "Before using the TYVASO Inhalation System, you should:" }

{ "type": "ul", "children": [ "Wash your hands\n\n", "Make sure the device is NOT connected to a power source", "Make sure the device is resting on a stable, flat surface during assembly" ], "text": "" }

ONLY USE DISTILLED WATER in the device. Distilled water is highly purified water that can be purchased at most grocery stores and pharmacies. It is necessary for the device to function properly. If you use another type of water (such as bottled or tap water), the device may not function properly.

{ "type": "p", "children": [], "text": "\nONLY USE DISTILLED WATER in the device. Distilled water is highly purified water that can be purchased at most grocery stores and pharmacies. It is necessary for the device to function properly. If you use another type of water (such as bottled or tap water), the device may not function properly." }

1 Fill the white chamber inside the device with approximately 45 mL of distilled water (about 1.5 ounces), using the water level cup provided. Fill the cup until water level is between the two arrow markings.

{ "type": "p", "children": [], "text": "\n1\nFill the white chamber inside the device with approximately 45 mL of distilled water (about 1.5 ounces), using the water level cup provided. Fill the cup until water level is between the two arrow markings." }

There is a silver sensor on the inside wall of the chamber. The water level should be above the silver sensor and below the blue ring in the device chamber. DO NOT OVERFILL the chamber, or the medicine cup will not fit correctly. Check the water level after filling the chamber.

{ "type": "p", "children": [], "text": "There is a silver sensor on the inside wall of the chamber. The water level should be above the silver sensor and below the blue ring in the device chamber. DO NOT OVERFILL the chamber, or the medicine cup will not fit correctly. Check the water level after filling the chamber." }

2 Obtain one (1) medicine cup and inspect it for any damage, holes, cracks, or dents. Do not use the medicine cup if it is damaged.

{ "type": "p", "children": [], "text": "\n2\nObtain one (1) medicine cup and inspect it for any damage, holes, cracks, or dents. Do not use the medicine cup if it is damaged." }

Insert the empty medicine cup into the chamber of the device, making sure that the cup's bottom tip is in the distilled water. The cup will sit on the blue ring.

{ "type": "p", "children": [], "text": "Insert the empty medicine cup into the chamber of the device, making sure that the cup's bottom tip is in the distilled water. The cup will sit on the blue ring." }

3 Carefully cut open the top of the foil pouch, making sure not to cut the ampules. Each pouch contains four (4) ampules.

{ "type": "p", "children": [], "text": "\n3\nCarefully cut open the top of the foil pouch, making sure not to cut the ampules. Each pouch contains four (4) ampules." }

Remove one (1) ampule of TYVASO. Keep unused ampules in the foil pouch because the TYVASO medicine is sensitive to light.

{ "type": "p", "children": [], "text": "Remove one (1) ampule of TYVASO. Keep unused ampules in the foil pouch because the TYVASO medicine is sensitive to light." }

One (1) ampule contains enough medicine for one (1) day of treatment no matter how many breaths your doctor has prescribed.

{ "type": "p", "children": [], "text": "One (1) ampule contains enough medicine for one (1) day of treatment no matter how many breaths your doctor has prescribed." }

4 Gently hold the ampule in the upright (topup) position and twist off its top.

{ "type": "p", "children": [], "text": "\n4\nGently hold the ampule in the upright (topup) position and twist off its top." }

5 Point the ampule straight down toward the medicine cup's center to avoid spills.

{ "type": "p", "children": [], "text": "\n5\nPoint the ampule straight down toward the medicine cup's center to avoid spills." }

Gently squeeze the medicine out of the ampule into the medicine cup. Squeeze until it is empty. Check to see that all of the medicine is in the medicine cup.

{ "type": "p", "children": [], "text": "Gently squeeze the medicine out of the ampule into the medicine cup. Squeeze until it is empty. Check to see that all of the medicine is in the medicine cup." }

Assembling the Inhalation Device

{ "type": "p", "children": [], "text": "\nAssembling the Inhalation Device\n" }

The TYVASO Inhalation System is designed so the parts only fit together properly one way.

{ "type": "p", "children": [], "text": "The TYVASO Inhalation System is designed so the parts only fit together properly one way." }

When the device is assembled correctly, the parts should fit together easily.

{ "type": "p", "children": [], "text": "When the device is assembled correctly, the parts should fit together easily." }

Do not force the parts together.

{ "type": "p", "children": [], "text": "Do not force the parts together." }

1 Visually check to make sure the blue plastic baffle plate and black ring are correctly placed in the dome assembly. They should appear as they do in the images below.

{ "type": "p", "children": [], "text": "\n1\nVisually check to make sure the blue plastic baffle plate and black ring are correctly placed in the dome assembly. They should appear as they do in the images below." }

In the unlikely event that the baffle plate is loose or disconnected, use a new dome assembly. If you need to order a new dome assembly, contact your specialty pharmacy provider.

{ "type": "p", "children": [], "text": "In the unlikely event that the baffle plate is loose or disconnected, use a new dome assembly. If you need to order a new dome assembly, contact your specialty pharmacy provider." }

2 Align the raised circle on the side of the dome assembly with the circle on the side of the device. Push down and screw the dome assembly onto the device clockwise (right) until you hear a click, indicating the dome assembly is fully connected to the medicine cup. When the dome assembly is properly aligned, the filter shell port will point to the back of the device.

{ "type": "p", "children": [], "text": "\n2\nAlign the raised circle on the side of the dome assembly with the circle on the side of the device. Push down and screw the dome assembly onto the device clockwise (right) until you hear a click, indicating the dome assembly is fully connected to the medicine cup. When the dome assembly is properly aligned, the filter shell port will point to the back of the device." }

3 Insert the inhalation piece into the upper opening of the dome assembly and rotate toward the front of the device. Gently push down the inhalation piece to make sure it is securely inserted in the dome assembly.

{ "type": "p", "children": [], "text": "\n3\nInsert the inhalation piece into the upper opening of the dome assembly and rotate toward the front of the device. Gently push down the inhalation piece to make sure it is securely inserted in the dome assembly." }

4 Insert the mouthpiece into the inhalation piece.

{ "type": "p", "children": [], "text": "\n4\nInsert the mouthpiece into the inhalation piece." }

5 Each day you will need to use a new filter membrane in each filter shell.

{ "type": "p", "children": [], "text": "\n5\nEach day you will need to use a new filter membrane in each filter shell." }

To install a new filter membrane:

{ "type": "p", "children": [], "text": "To install a new filter membrane:" }

{ "type": "ul", "children": [ "Open the filter shell by unscrewing the two (2) halves.", "Place a new filter membrane in one (1) of the filter shell halves.", "Close the filter shell by screwing the two (2) halves together until you can twist no further." ], "text": "" }

Note: New filter shells come with fresh filter membranes already installed.

{ "type": "p", "children": [], "text": "Note: New filter shells come with fresh filter membranes already installed." }

6 Insert one (1) of the filter shells into the filter shell port on the side of the dome assembly and insert the other filter shell into the port on the bottom of the inhalation piece. The two (2) filter shells are identical and can be used in either opening.

{ "type": "p", "children": [], "text": "\n6\nInsert one (1) of the filter shells into the filter shell port on the side of the dome assembly and insert the other filter shell into the port on the bottom of the inhalation piece. The two (2) filter shells are identical and can be used in either opening." }

Make sure to insert the filter shells straight into their ports, rather than at an angle. If necessary, rotate the inhalation piece so you can insert the filter shell without the device getting in the way.

{ "type": "p", "children": [], "text": "Make sure to insert the filter shells straight into their ports, rather than at an angle. If necessary, rotate the inhalation piece so you can insert the filter shell without the device getting in the way." }

7 When the device is fully assembled, it should appear as it does in the photo below.

{ "type": "p", "children": [], "text": "\n7\nWhen the device is fully assembled, it should appear as it does in the photo below." }

For convenience, rotate the inhalation piece so you can best see the indicator lights and display screen, which provide important prompts during your treatment.

{ "type": "p", "children": [], "text": "For convenience, rotate the inhalation piece so you can best see the indicator lights and display screen, which provide important prompts during your treatment." }

Turning On the Inhalation Device

{ "type": "p", "children": [], "text": "\nTurning On the Inhalation Device\n" }

1 Connect your device to one (1) of the power source options by plugging one end of the power cord into the back of the inhalation device and the other end into the power source.

{ "type": "p", "children": [], "text": "\n1\nConnect your device to one (1) of the power source options by plugging one end of the power cord into the back of the inhalation device and the other end into the power source." }

If using the AC wall plug, make sure to plug the output cable into the device before plugging adapter into the power source.

{ "type": "p", "children": [], "text": "If using the AC wall plug, make sure to plug the output cable into the device before plugging adapter into the power source." }

If using the rechargeable battery, make sure it is not also plugged into the AC wall plug.

{ "type": "p", "children": [], "text": "If using the rechargeable battery, make sure it is not also plugged into the AC wall plug." }

2 To turn on the device, press and hold the ON/OFF button for approximately three (3) seconds. When you hear a short beep and the yellow status light is illuminated, release the ON/OFF button. Remember to press the center of the ON/OFF button when powering the device on or off.

{ "type": "p", "children": [], "text": "\n2\nTo turn on the device, press and hold the ON/OFF button for approximately three (3) seconds. When you hear a short beep and the yellow status light is illuminated, release the ON/OFF button. Remember to press the center of the ON/OFF button when powering the device on or off." }

When the power is on, the display screen will show the last number of breaths programmed and a yellow light will appear next to the screen.

{ "type": "p", "children": [], "text": "When the power is on, the display screen will show the last number of breaths programmed and a yellow light will appear next to the screen." }

Make sure the number matches the prescribed number of breaths for that treatment session. If it does not match, see the next page for instructions on setting the number of breaths in a treatment session.

{ "type": "p", "children": [], "text": "Make sure the number matches the prescribed number of breaths for that treatment session. If it does not match, see the next page for instructions on setting the number of breaths in a treatment session." }

Setting the Number of Breaths in a Treatment Session

{ "type": "p", "children": [], "text": "\nSetting the Number of Breaths in a Treatment Session\n" }

You will inhale TYVASO during four (4) treatment sessions each day. During each treatment session, you will take a series of breaths through the mouthpiece of the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "You will inhale TYVASO during four (4) treatment sessions each day. During each treatment session, you will take a series of breaths through the mouthpiece of the TYVASO Inhalation System." }

Your doctor will prescribe the number of breaths you should inhale in each treatment session.

{ "type": "p", "children": [], "text": "Your doctor will prescribe the number of breaths you should inhale in each treatment session." }

You should record the number of breaths in your Treatment Tracker.

{ "type": "p", "children": [], "text": "You should record the number of breaths in your Treatment Tracker." }

1 Make sure the device is powered off. To power off the device, press and hold the ON/OFF button for three (3) seconds. When you hear a short beep and the display screen turns off, release the ON/ OFF button.

{ "type": "p", "children": [], "text": "\n1\nMake sure the device is powered off. To power off the device, press and hold the ON/OFF button for three (3) seconds. When you hear a short beep and the display screen turns off, release the ON/ OFF button." }

To set the number of breaths, press and hold both the START/STOP and ON/OFF buttons at the same time until the display flashes and the device emits three (3) short beeps.

{ "type": "p", "children": [], "text": "To set the number of breaths, press and hold both the START/STOP and ON/OFF buttons at the same time until the display flashes and the device emits three (3) short beeps." }

The flashing display indicates the inhalation device is in breath programming mode. You cannot begin a treatment while the display is flashing.

{ "type": "p", "children": [], "text": "The flashing display indicates the inhalation device is in breath programming mode. You cannot begin a treatment while the display is flashing." }

2 To increase the number of breaths press the + (ON/OFF) button.

{ "type": "p", "children": [], "text": "\n2\nTo increase the number of breaths press the + (ON/OFF) button." }

To decrease the number of breaths press the – (START/STOP) button.

{ "type": "p", "children": [], "text": "To decrease the number of breaths press the – (START/STOP) button." }

Remember to press in the center of the buttons.

{ "type": "p", "children": [], "text": "Remember to press in the center of the buttons." }

3 Once you have entered your prescribed number of breaths, remove your hands from the device and wait approximately 15 seconds.

{ "type": "p", "children": [], "text": "\n3\nOnce you have entered your prescribed number of breaths, remove your hands from the device and wait approximately 15 seconds." }

After approximately 15 seconds, the display will stop flashing and the device will emit three (3) short beeps, indicating that it has saved the new number of breaths. The new number of breaths will appear on the display.

{ "type": "p", "children": [], "text": "After approximately 15 seconds, the display will stop flashing and the device will emit three (3) short beeps, indicating that it has saved the new number of breaths. The new number of breaths will appear on the display." }

Make sure the number of breaths on the display matches the number of breaths in your prescription. If the numbers do not match, repeat steps 1-3.

{ "type": "p", "children": [], "text": "Make sure the number of breaths on the display matches the number of breaths in your prescription. If the numbers do not match, repeat steps 1-3." }

Inhaling Your Medicine, TYVASO® (treprostinil) Inhalation Solution

{ "type": "p", "children": [], "text": "\nInhaling Your Medicine, TYVASO® (treprostinil) Inhalation Solution\n" }

You will inhale TYVASO during four (4) treatment sessions each day. During each treatment session, you will take a series of breaths through the mouthpiece of the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "You will inhale TYVASO during four (4) treatment sessions each day. During each treatment session, you will take a series of breaths through the mouthpiece of the TYVASO Inhalation System." }

Inhalation Tips

{ "type": "p", "children": [], "text": "\nInhalation Tips\n" }

Technique:

{ "type": "p", "children": [], "text": "\nTechnique:\n" }

When breathing each TYVASO treatment, be sure to keep the device level, directing the flow of medicine into the throat and not toward the roof of the mouth.

{ "type": "p", "children": [], "text": "When breathing each TYVASO treatment, be sure to keep the device level, directing the flow of medicine into the throat and not toward the roof of the mouth." }

Seal your lips around the mouthpiece to ensure that you can inhale the full amount of TYVASO after it is produced by the device.

{ "type": "p", "children": [], "text": "Seal your lips around the mouthpiece to ensure that you can inhale the full amount of TYVASO after it is produced by the device." }

Inhalation:

{ "type": "p", "children": [], "text": "\nInhalation:\n" }

Each breath should last approximately three (3) seconds, breathing "normal full breaths." Do not hold your breath. Exhale normally and prepare for the next breath.

{ "type": "p", "children": [], "text": "Each breath should last approximately three (3) seconds, breathing \"normal full breaths.\" Do not hold your breath. Exhale normally and prepare for the next breath." }

1 Hold the device upright as shown below. Make sure you can see the display screen and lights clearly and that your hands do not cover the display screen or lights while holding device. If the inhalation piece or mouthpiece block your view of the display screen or lights, move the inhalation piece so you can best see them.

{ "type": "p", "children": [], "text": "\n1\nHold the device upright as shown below. Make sure you can see the display screen and lights clearly and that your hands do not cover the display screen or lights while holding device. If the inhalation piece or mouthpiece block your view of the display screen or lights, move the inhalation piece so you can best see them." }

2 Perform steps A-G to complete one (1) treatment session.Follow the instructions exactly to make sure you receive the correct medication dose.

{ "type": "p", "children": [], "text": "\n2\nPerform steps A-G to complete one (1) treatment session.Follow the instructions exactly to make sure you receive the correct medication dose." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">A</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-52.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"><span class="Bold">B</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-53.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"><span class="Bold">C</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-54.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"><span class="Bold">D</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-55.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="left">Press the START/STOP button to begin treatment.</td><td align="left">The status light turns green and the device emits two (2) short beeps.</td><td align="left">While the device emits one (1) long beep, exhale completely.</td><td align="left">After the device emits a short beep and while the inhalation indicator light is flashing green, place your lips securely around the mouthpiece and inhale slowly for the duration of the beep (at least three (3) seconds). Exhale normally, mark a circle in the Treatment Tracker and prepare for the next breath.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">A</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-52.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\"><span class=\"Bold\">B</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-53.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\"><span class=\"Bold\">C</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-54.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\"><span class=\"Bold\">D</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-55.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"left\">Press the START/STOP button to begin treatment.</td><td align=\"left\">The status light turns green and the device emits two (2) short beeps.</td><td align=\"left\">While the device emits one (1) long beep, exhale completely.</td><td align=\"left\">After the device emits a short beep and while the inhalation indicator light is flashing green, place your lips securely around the mouthpiece and inhale slowly for the duration of the beep (at least three (3) seconds). Exhale normally, mark a circle in the Treatment Tracker and prepare for the next breath.</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="75%"> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="34%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">E</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-57.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"><span class="Bold">F</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-58.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"><span class="Bold">G</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-59.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="left">Repeat steps B through D for the number of prescribed breaths and until the display counts down to "00".</td><td align="left">After the final breath, the display screen will show "00" then "En," indicating the treatment session is complete.<br/> <br/>Check the number of breaths you inhaled on the Treatment Tracker.</td><td align="left">To turn off the device, press and hold the ON/OFF button for three (3) seconds and then release.<br/> <br/>If the device is left in "En" mode for more than 60 seconds, it will turn off automatically.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"75%\">\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<col align=\"left\" valign=\"top\" width=\"34%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">E</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-57.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\"><span class=\"Bold\">F</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-58.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\"><span class=\"Bold\">G</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-59.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"left\">Repeat steps B through D for the number of prescribed breaths and until the display counts down to \"00\".</td><td align=\"left\">After the final breath, the display screen will show \"00\" then \"En,\" indicating the treatment session is complete.<br/>\n<br/>Check the number of breaths you inhaled on the Treatment Tracker.</td><td align=\"left\">To turn off the device, press and hold the ON/OFF button for three (3) seconds and then release.<br/>\n<br/>If the device is left in \"En\" mode for more than 60 seconds, it will turn off automatically.</td>\n</tr>\n</tbody>\n</table></div>" }

3 To pause the treatment between breaths, press the START/STOP button. The display screen will show "PA."

{ "type": "p", "children": [], "text": "\n3\nTo pause the treatment between breaths, press the START/STOP button. The display screen will show \"PA.\"" }

To resume treatment, press START/ STOP again. "PA" will disappear and the display screen will show the number of breaths remaining.

{ "type": "p", "children": [], "text": "To resume treatment, press START/ STOP again. \"PA\" will disappear and the display screen will show the number of breaths remaining." }

If the device is disconnected from its power source for any reason (for example, a power failure), reconnect the device to a power source. Follow the instructions on page 13 to turn on the device. The display will show how many breaths are left in that treatment session. Press the START/STOP button to continue your treatment session.

{ "type": "p", "children": [], "text": "If the device is disconnected from its power source for any reason (for example, a power failure), reconnect the device to a power source. Follow the instructions on page 13 to turn on the device. The display will show how many breaths are left in that treatment session. Press the START/STOP button to continue your treatment session." }

Storing the TYVASO Inhalation System Between Treatment Sessions

{ "type": "p", "children": [], "text": "\nStoring the TYVASO Inhalation System Between Treatment Sessions\n" }

If you have more treatment sessions left in the day, perform the following steps.

{ "type": "p", "children": [], "text": "If you have more treatment sessions left in the day, perform the following steps." }

If you have completed your last treatment session of the day, skip to Cleaning and Maintenance of the TYVASO Inhalation System (see page 24).

{ "type": "p", "children": [], "text": "If you have completed your last treatment session of the day, skip to Cleaning and Maintenance of the TYVASO Inhalation System (see page 24)." }

Be sure to pack all parts, including a backup power supply, in the carry case whenever transporting your device.

{ "type": "p", "children": [], "text": "Be sure to pack all parts, including a backup power supply, in the carry case whenever transporting your device." }

1 Disconnect the device from its power source.

{ "type": "p", "children": [], "text": "\n1\nDisconnect the device from its power source." }

2 Remove both filter shells.

{ "type": "p", "children": [], "text": "\n2\nRemove both filter shells." }

Do NOT remove the filter membranes from filter shells until after the last treatment session of the day.

{ "type": "p", "children": [], "text": "Do NOT remove the filter membranes from filter shells until after the last treatment session of the day." }

3 Remove the mouthpiece.

{ "type": "p", "children": [], "text": "\n3\nRemove the mouthpiece." }

4 Remove the inhalation piece.

{ "type": "p", "children": [], "text": "\n4\nRemove the inhalation piece." }

5 Leave the dome assembly and medicine cup (with the medicine still in it) connected to the device.

{ "type": "p", "children": [], "text": "\n5\nLeave the dome assembly and medicine cup (with the medicine still in it) connected to the device." }

6 Insert a plug into each of the open holes on the dome assembly to prevent the medicine from spilling out.

{ "type": "p", "children": [], "text": "\n6\nInsert a plug into each of the open holes on the dome assembly to prevent the medicine from spilling out." }

7 The inhalation device with the plugged dome assembly and all the accessories can be stored in the carrying case between treatment sessions.

{ "type": "p", "children": [], "text": "\n7\nThe inhalation device with the plugged dome assembly and all the accessories can be stored in the carrying case between treatment sessions." }

Cleaning and Maintenance of the TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nCleaning and Maintenance of the TYVASO Inhalation System\n" }

End of Day Cleaning of the Accessories

{ "type": "p", "children": [], "text": "\nEnd of Day Cleaning of the Accessories\n" }

1 Disconnect the device from the power source.

{ "type": "p", "children": [], "text": "\n1\nDisconnect the device from the power source." }

2 Remove both filter shells.

{ "type": "p", "children": [], "text": "\n2\nRemove both filter shells." }

3 Open the filter shells by twisting in opposite directions.

{ "type": "p", "children": [], "text": "\n3\nOpen the filter shells by twisting in opposite directions." }

Remove and discard the used filter membranes.

{ "type": "p", "children": [], "text": "Remove and discard the used filter membranes." }

4 Remove the mouthpiece.

{ "type": "p", "children": [], "text": "\n4\nRemove the mouthpiece." }

5 Remove the inhalation piece.

{ "type": "p", "children": [], "text": "\n5\nRemove the inhalation piece." }

6 Remove the dome assembly by turning it counter-clockwise (to the left). The medicine cup should stay attached to the dome assembly.

{ "type": "p", "children": [], "text": "\n6\nRemove the dome assembly by turning it counter-clockwise (to the left). The medicine cup should stay attached to the dome assembly." }

7 Remove the medicine cup by gently squeezing on the sides where it is attached to the dome assembly. Empty the medicine cup into a sink or waste basket, then discard the medicine cup.

{ "type": "p", "children": [], "text": "\n7\nRemove the medicine cup by gently squeezing on the sides where it is attached to the dome assembly. Empty the medicine cup into a sink or waste basket, then discard the medicine cup." }

Be careful not to spill the medicine when removing or discarding the medicine cup.

{ "type": "p", "children": [], "text": "Be careful not to spill the medicine when removing or discarding the medicine cup." }

8 Empty the distilled water from the chamber and let the inhalation device air dry upside down. You can wipe the chamber with a soft cloth or paper towel to collect water.

{ "type": "p", "children": [], "text": "\n8\nEmpty the distilled water from the chamber and let the inhalation device air dry upside down. You can wipe the chamber with a soft cloth or paper towel to collect water." }

9 Clean the accessories (pictured below) by hand in mild, soapy, warm water, then rinse them thoroughly with water. Allow accessories to air dry.

{ "type": "p", "children": [], "text": "\n9\nClean the accessories (pictured below) by hand in mild, soapy, warm water, then rinse them thoroughly with water. Allow accessories to air dry." }

10 Once all the items are dry, the filter shells, inhalation piece, mouthpiece, dome assembly, and inhalation device can be stored in the carrying case until the next day's treatment sessions.

{ "type": "p", "children": [], "text": "\n10\nOnce all the items are dry, the filter shells, inhalation piece, mouthpiece, dome assembly, and inhalation device can be stored in the carrying case until the next day's treatment sessions." }

Weekly Cleaning

{ "type": "p", "children": [], "text": "\nWeekly Cleaning\n" }

{ "type": "ul", "children": [ "Once a week, use a clean cloth to wipe the interior of the inhalation device chamber, be sure to wipe the disc in the bottom of the device. You may wipe the exterior of the device with a damp cloth if the lights or buttons become difficult to see. Proper cleaning will help to avoid corrosion and leaks and keep your device working properly." ], "text": "" }

Monthly Refill Kit

{ "type": "p", "children": [], "text": "\nMonthly Refill Kit\n" }

{ "type": "ul", "children": [ "Once a month, you will receive a refill kit that will come with a new set of accessories from your specialty pharmacy provider. Inspect the shipment to be sure all parts are included (see page 7). Once the new kit has arrived, discard the used dome assembly, inhalation piece, mouthpiece, and two (2) filter shells. Do not recycle the used accessories." ], "text": "" }

Device Replacement

{ "type": "p", "children": [], "text": "\nDevice Replacement\n" }

{ "type": "ul", "children": [ "The inhalation device should be replaced every two (2) years from your first day of use. Replacement inhalation devices will be supplied by your specialty pharmacy provider." ], "text": "" }

Charging Your TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nCharging Your TYVASO Inhalation System\n" }

Rechargeable Battery

{ "type": "p", "children": [], "text": "\nRechargeable Battery\n" }

The rechargeable battery is supplied with its own instructions for use. Refer to these instructions for more information.

{ "type": "p", "children": [], "text": "The rechargeable battery is supplied with its own instructions for use. Refer to these instructions for more information." }

{ "type": "ul", "children": [ "Your TYVASO Inhalation System is supplied with a portable, rechargeable battery. Do NOT use other batteries.\n\n", "Your battery can only be charged by using one (1) of the AC wall plugs that comes with your inhalation device.\n\n", "To check the battery's voltage level, press and hold the blue button on the front of the battery. You can only check the battery's voltage level when the battery is not plugged into a power source.\nThe light below the button will turn on and indicate the battery's voltage level. A red light indicates the battery needs to be charged. A green light indicates the battery is ready to operate the device.\n\n" ], "text": "" }

{ "type": "ul", "children": [ "To charge the battery, connect the AC wall plug to the battery pack and plug the AC wall plug into an outlet.\nA yellow light on the front of the battery will turn on, indicating that the battery is charging.", "Your battery may take up to 40 hours to fully charge. It is not possible to use the TYVASO Inhalation System with the battery while it is recharging.\nA fully charged battery will typically last up to 200 inhalations. A battery charged for one (1) night (about 10 hours) will typically last up to one (1) day of therapy (about 40 inhalations)." ], "text": "" }

{ "type": "ul", "children": [ "You should connect the charged battery to the TYVASO Inhalation System only for your treatment. When using the battery pack to power the device, make sure the battery is not plugged into a power source.\n\n", "After your treatment session is complete, remove the power plug of the battery from the device.", "Charge the battery whenever you are not using it to power the inhalation device.", "Always have your AC wall plug or 12V DC adapter available for backup, in case the battery is not charged." ], "text": "" }

Troubleshooting the TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nTroubleshooting the TYVASO Inhalation System\n" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="34%"/> <col align="left" valign="top" width="33%"/> <col align="left" valign="top" width="33%"/> <thead> <tr class="First Last"> <th align="left">Problem</th><th align="left">Possible causes</th><th align="left">Corrective actions</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" rowspan="4"><span class="Bold">Low battery (LB)</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-93.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"> <ul class="Disc"> <li>Low battery</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the battery from the device. Charge the battery by attaching it to the AC wall plug and outlet.</li> <li>Use an alternative power source, such as the AC wall plug or 12V DC adapter, for treatment.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>Defective adapter (AC wall plug or 12V DC adapter)</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Ensure that the plug is properly connected to an outlet.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>AC wall plug is still plugged into battery and battery is connected to device.</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Turn off device (see page 14).</li> <li>Disconnect AC wall plug from battery.</li> <li>Check battery status, following instructions on page 28.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"></td><td align="left"> <ul class="Disc"> <li>If device is properly powered and still does not function, contact your specialty pharmacy provider for a replacement.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" rowspan="4"><span class="Bold">Low hydrogen (LH)</span><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-94.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"> <ul class="Disc"> <li>Device chamber is empty or distilled water level in the device chamber is too low.<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-95.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source.<br/>Remove the dome assembly carefully, making sure not to spill its medicine. Empty the device chamber then refill it with distilled water (see page 8) and reconnect the dome assembly (see page 10).</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>The distilled water you are using is too purified</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Empty device chamber. Add one (1) teaspoon of tap water to the water fill cup. Fill cup with distilled water up to level between the two arrow markings on cup (see page 8). Pour cup's contents into device chamber.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>The sensor has a thin layer of build-up</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Clean sensor and interior surfaces of water chamber with a clean cloth.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"></td><td align="left"> <ul class="Disc"> <li>If device is properly powered and still does not function, contact your specialty pharmacy provider for a replacement.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" rowspan="4"><span class="Bold">No medicine comes out of the device during a treatment session</span></td><td align="left"> <ul class="Disc"> <li>No TYVASO<span class="Sup">®</span> (treprostinil) Inhalation Solution in the medicine cup<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-96.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Fill medicine cup with one (1) ampule of TYVASO.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>Damaged medicine cup<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-97.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Replace the medicine cup.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>Distilled water level in the device chamber is too high<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-98.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Empty the device chamber then refill it with 45 mL of distilled water.<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-99.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>Multiple medicine cups attached to the dome assembly<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-100.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Remove and dispose of all medicine cups in the device. Insert a single, new medicine cup into device chamber and fill with one (1) ampule of TYVASO.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"><span class="Bold">Difficult to breathe in medicine through the mouthpiece</span></td><td align="left"> <ul class="Disc"> <li>Filter membrane is clogged</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Replace filter membrane (see page 11).<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-101.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" rowspan="3"><span class="Bold">No "click" was heard when attaching the dome assembly</span></td><td align="left"> <ul class="Disc"> <li>No medicine cup in the chamber of the device</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Insert an empty medicine cup into the chamber of the device and fill it with one (1) ampule of TYVASO.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>Multiple medicine cups attached to the dome assembly<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-102.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Remove and dispose of all medicine cups in the device. Insert a single, new medicine cup into device chamber and fill with one (1) ampule of TYVASO.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left"> <ul class="Disc"> <li>Dome assembly is not securely in place<img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-103.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></li> </ul> </td><td align="left"> <ul class="Disc"> <li>Unplug the device from its power source. Align the circle on the side of the dome assembly with the circle on the side of the device. Push down and screw the dome assembly onto the device clockwise (right) until you hear a click, indicating the dome assembly is fully connected to the medicine cup.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" rowspan="2"><span class="Bold">Loss of power during treatment</span></td><td align="left"> <ul class="Disc"> <li>Device is disconnected from its power source</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Reconnect the device to a power source and press the ON/OFF button to turn on the device. The display will show how many breaths are left in that treatment session. Press the START/STOP button to continue your treatment session.</li> </ul> </td> </tr> <tr class="Last"> <td align="left"> <ul class="Disc"> <li>Power source is temporarily disrupted (for example, electricity interruption due to a storm)</li> </ul> </td><td align="left"> <ul class="Disc"> <li>Reconnect the device to a power source and turn on the device (see page 13). The display will show how many breaths are left in that treatment session. Press the START/ STOP button to continue your treatment session.</li> </ul> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"34%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<col align=\"left\" valign=\"top\" width=\"33%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\">Problem</th><th align=\"left\">Possible causes</th><th align=\"left\">Corrective actions</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" rowspan=\"4\"><span class=\"Bold\">Low battery (LB)</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-93.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Low battery</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the battery from the device. Charge the battery by attaching it to the AC wall plug and outlet.</li>\n<li>Use an alternative power source, such as the AC wall plug or 12V DC adapter, for treatment.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Defective adapter (AC wall plug or 12V DC adapter)</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Ensure that the plug is properly connected to an outlet.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>AC wall plug is still plugged into battery and battery is connected to device.</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Turn off device (see page 14).</li>\n<li>Disconnect AC wall plug from battery.</li>\n<li>Check battery status, following instructions on page 28.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\"></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>If device is properly powered and still does not function, contact your specialty pharmacy provider for a replacement.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" rowspan=\"4\"><span class=\"Bold\">Low hydrogen (LH)</span><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-94.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Device chamber is empty or distilled water level in the device chamber is too low.<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-95.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source.<br/>Remove the dome assembly carefully, making sure not to spill its medicine. Empty the device chamber then refill it with distilled water (see page 8) and reconnect the dome assembly (see page 10).</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>The distilled water you are using is too purified</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Empty device chamber. Add one (1) teaspoon of tap water to the water fill cup. Fill cup with distilled water up to level between the two arrow markings on cup (see page 8). Pour cup's contents into device chamber.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>The sensor has a thin layer of build-up</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Clean sensor and interior surfaces of water chamber with a clean cloth.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\"></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>If device is properly powered and still does not function, contact your specialty pharmacy provider for a replacement.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" rowspan=\"4\"><span class=\"Bold\">No medicine comes out of the device during a treatment session</span></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>No TYVASO<span class=\"Sup\">®</span> (treprostinil) Inhalation Solution in the medicine cup<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-96.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Fill medicine cup with one (1) ampule of TYVASO.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Damaged medicine cup<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-97.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Replace the medicine cup.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Distilled water level in the device chamber is too high<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-98.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Empty the device chamber then refill it with 45 mL of distilled water.<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-99.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Multiple medicine cups attached to the dome assembly<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-100.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Remove and dispose of all medicine cups in the device. Insert a single, new medicine cup into device chamber and fill with one (1) ampule of TYVASO.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">Difficult to breathe in medicine through the mouthpiece</span></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Filter membrane is clogged</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Replace filter membrane (see page 11).<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-101.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" rowspan=\"3\"><span class=\"Bold\">No \"click\" was heard when attaching the dome assembly</span></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>No medicine cup in the chamber of the device</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Insert an empty medicine cup into the chamber of the device and fill it with one (1) ampule of TYVASO.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Multiple medicine cups attached to the dome assembly<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-102.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Remove and dispose of all medicine cups in the device. Insert a single, new medicine cup into device chamber and fill with one (1) ampule of TYVASO.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Dome assembly is not securely in place<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-103.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Unplug the device from its power source. Align the circle on the side of the dome assembly with the circle on the side of the device. Push down and screw the dome assembly onto the device clockwise (right) until you hear a click, indicating the dome assembly is fully connected to the medicine cup.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" rowspan=\"2\"><span class=\"Bold\">Loss of power during treatment</span></td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Device is disconnected from its power source</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Reconnect the device to a power source and press the ON/OFF button to turn on the device. The display will show how many breaths are left in that treatment session. Press the START/STOP button to continue your treatment session.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">\n<ul class=\"Disc\">\n<li>Power source is temporarily disrupted (for example, electricity interruption due to a storm)</li>\n</ul>\n</td><td align=\"left\">\n<ul class=\"Disc\">\n<li>Reconnect the device to a power source and turn on the device (see page 13). The display will show how many breaths are left in that treatment session. Press the START/ STOP button to continue your treatment session.</li>\n</ul>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Specifications

{ "type": "p", "children": [], "text": "\nSpecifications\n" }

Inhalation Device

{ "type": "p", "children": [], "text": "\nInhalation Device\n" }

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <tbody class="Headless"> <tr class="First"> <td align="left">Model</td><td align="left"><span class="Bold">TD-100/A</span></td> </tr> <tr> <td align="left">Size</td><td align="left"><span class="Bold">98 × 66 × 105 mm</span></td> </tr> <tr> <td align="left">Weight, inhalation device</td><td align="left"><span class="Bold">280 g (9.9 ounces)</span></td> </tr> <tr> <td align="left">Types of power supply</td><td align="left"><span class="Bold">AC wall plug<br/>12V DC adapter<br/>Rechargeable battery</span></td> </tr> <tr> <td align="left">Power input</td><td align="left"><span class="Bold">12V DC, 1.5A maximum</span></td> </tr> <tr> <td align="left">Operating power consumption</td><td align="left"><span class="Bold">18 Watt maximum</span></td> </tr> <tr> <td align="left">Ultrasonic frequency</td><td align="left"><span class="Bold">2.4 MHz (nominal)</span></td> </tr> <tr> <td align="left">Nebulization rate</td><td align="left"><span class="Bold">0.50 - 0.55 mg/min (0.9% Saline)</span></td> </tr> <tr> <td align="left">Medicine cup capacity</td><td align="left"><span class="Bold">6 mL, nominal</span></td> </tr> <tr> <td align="left">Contact fluid chamber capacity</td><td align="left"><span class="Bold">45 mL, nominal</span></td> </tr> <tr> <td align="left">Electric protection class</td><td align="left"><span class="Bold">II Type B</span></td> </tr> <tr> <td align="left">Storage temperature/humidity</td><td align="left"><span class="Bold">-5 to 40°C/20-80% relative humidity</span></td> </tr> <tr class="Last"> <td align="left">Operating temperature/humidity</td><td align="left"><span class="Bold">15 to 25°C/40-75% relative humidity</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\">Model</td><td align=\"left\"><span class=\"Bold\">TD-100/A</span></td>\n</tr>\n<tr>\n<td align=\"left\">Size</td><td align=\"left\"><span class=\"Bold\">98 × 66 × 105 mm</span></td>\n</tr>\n<tr>\n<td align=\"left\">Weight, inhalation device</td><td align=\"left\"><span class=\"Bold\">280 g (9.9 ounces)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Types of power supply</td><td align=\"left\"><span class=\"Bold\">AC wall plug<br/>12V DC adapter<br/>Rechargeable battery</span></td>\n</tr>\n<tr>\n<td align=\"left\">Power input</td><td align=\"left\"><span class=\"Bold\">12V DC, 1.5A maximum</span></td>\n</tr>\n<tr>\n<td align=\"left\">Operating power consumption</td><td align=\"left\"><span class=\"Bold\">18 Watt maximum</span></td>\n</tr>\n<tr>\n<td align=\"left\">Ultrasonic frequency</td><td align=\"left\"><span class=\"Bold\">2.4 MHz (nominal)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Nebulization rate</td><td align=\"left\"><span class=\"Bold\">0.50 - 0.55 mg/min (0.9% Saline)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Medicine cup capacity</td><td align=\"left\"><span class=\"Bold\">6 mL, nominal</span></td>\n</tr>\n<tr>\n<td align=\"left\">Contact fluid chamber capacity</td><td align=\"left\"><span class=\"Bold\">45 mL, nominal</span></td>\n</tr>\n<tr>\n<td align=\"left\">Electric protection class</td><td align=\"left\"><span class=\"Bold\">II Type B</span></td>\n</tr>\n<tr>\n<td align=\"left\">Storage temperature/humidity</td><td align=\"left\"><span class=\"Bold\">-5 to 40°C/20-80% relative humidity</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">Operating temperature/humidity</td><td align=\"left\"><span class=\"Bold\">15 to 25°C/40-75% relative humidity</span></td>\n</tr>\n</tbody>\n</table></div>" }

Packaging Dimensions (Approximate Length × Width × Height)

{ "type": "p", "children": [], "text": "\nPackaging Dimensions (Approximate Length × Width × Height)" }

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="60%"/> <col align="left" valign="top" width="40%"/> <tbody class="Headless"> <tr class="First"> <td align="left">Patient Starter Kit (PSK)</td><td align="left"><span class="Bold">12.2" × 14.3" × 16.0"</span></td> </tr> <tr> <td align="left">Monthly Refill Kit (MRK)</td><td align="left"><span class="Bold">9.9" × 6.1" × 16.1"</span></td> </tr> <tr class="Last"> <td align="left">Institutional Starter Kit (ISK)</td><td align="left"><span class="Bold">12.2" × 14.3" × 16.0"</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<col align=\"left\" valign=\"top\" width=\"60%\"/>\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\">Patient Starter Kit (PSK)</td><td align=\"left\"><span class=\"Bold\">12.2\" × 14.3\" × 16.0\"</span></td>\n</tr>\n<tr>\n<td align=\"left\">Monthly Refill Kit (MRK)</td><td align=\"left\"><span class=\"Bold\">9.9\" × 6.1\" × 16.1\"</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">Institutional Starter Kit (ISK)</td><td align=\"left\"><span class=\"Bold\">12.2\" × 14.3\" × 16.0\"</span></td>\n</tr>\n</tbody>\n</table></div>" }

TYVASO Mass and Particle Specifications for 9 breaths

{ "type": "p", "children": [], "text": "\nTYVASO Mass and Particle Specifications for 9 breaths\n" }

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="60%"/> <col align="left" valign="top" width="40%"/> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-3" name="footnote-3">*</a> </dt> <dd>n=108 data points from r=3 inhalation devices. Each data point was 9 breaths.</dd> <dt> <a href="#footnote-reference-4" name="footnote-4">†</a> </dt> <dd>n=216 data points from r=6 inhalation devices. Each data point was 1 breath.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="left">Mass Median Aerosol Diameter (MMAD)<a class="Sup" href="#footnote-3" name="footnote-reference-3">*</a></td><td align="left"><span class="Bold">mean = 2.0 μm<br/>SD = 0.3</span></td> </tr> <tr> <td align="left">Total Emitted Dose per Breath<a class="Sup" href="#footnote-4" name="footnote-reference-4">†</a></td><td align="left"><span class="Bold">mean = 6.0 μg<br/>SD = 0.4</span></td> </tr> <tr> <td align="left">Total Aerosol Mass<a class="Sup" href="#footnote-3">*</a></td><td align="left"><span class="Bold">mean = 58 μg<br/>SD = 5.9</span></td> </tr> <tr> <td align="left">Total Respirable Dose<a class="Sup" href="#footnote-3">*</a></td><td align="left"><span class="Bold">mean = 44.6 μg<br/>SD = 3.5</span></td> </tr> <tr> <td align="left">Respirable Fraction<a class="Sup" href="#footnote-3">*</a></td><td align="left"><span class="Bold">mean = 73%<br/>SD = 5%</span></td> </tr> <tr class="Last"> <td align="left">Geometric Standard Deviation (GSD)<a class="Sup" href="#footnote-3">*</a></td><td align="left"><span class="Bold">mean = 2.6 μm<br/>SD = 0.4</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<col align=\"left\" valign=\"top\" width=\"60%\"/>\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"2\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-3\" name=\"footnote-3\">*</a>\n</dt>\n<dd>n=108 data points from r=3 inhalation devices. Each data point was 9 breaths.</dd>\n<dt>\n<a href=\"#footnote-reference-4\" name=\"footnote-4\">†</a>\n</dt>\n<dd>n=216 data points from r=6 inhalation devices. Each data point was 1 breath.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\">Mass Median Aerosol Diameter (MMAD)<a class=\"Sup\" href=\"#footnote-3\" name=\"footnote-reference-3\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 2.0 μm<br/>SD = 0.3</span></td>\n</tr>\n<tr>\n<td align=\"left\">Total Emitted Dose per Breath<a class=\"Sup\" href=\"#footnote-4\" name=\"footnote-reference-4\">†</a></td><td align=\"left\"><span class=\"Bold\">mean = 6.0 μg<br/>SD = 0.4</span></td>\n</tr>\n<tr>\n<td align=\"left\">Total Aerosol Mass<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 58 μg<br/>SD = 5.9</span></td>\n</tr>\n<tr>\n<td align=\"left\">Total Respirable Dose<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 44.6 μg<br/>SD = 3.5</span></td>\n</tr>\n<tr>\n<td align=\"left\">Respirable Fraction<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 73%<br/>SD = 5%</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">Geometric Standard Deviation (GSD)<a class=\"Sup\" href=\"#footnote-3\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 2.6 μm<br/>SD = 0.4</span></td>\n</tr>\n</tbody>\n</table></div>" }

Accessories

{ "type": "p", "children": [], "text": "\nAccessories\n" }

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="80%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="2" valign="top">Note: Part number subject to change.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="left">ON-110HPA</td><td align="left"><span class="Bold">Rechargeable battery</span></td> </tr> <tr> <td align="left">ON-100Z</td><td align="left"><span class="Bold">12V DC adapter</span></td> </tr> <tr> <td align="left">ON-100N-US</td><td align="left"><span class="Bold">AC wall plug</span></td> </tr> <tr> <td align="left">ON-102/1/C</td><td align="left"><span class="Bold">Medicine cup, Quantity-16</span></td> </tr> <tr> <td align="left">ON-109</td><td align="left"><span class="Bold">Filter membranes</span></td> </tr> <tr> <td align="left">ON-120/C</td><td align="left"><span class="Bold">Plugs</span></td> </tr> <tr> <td align="left">ON-101/C</td><td align="left"><span class="Bold">Filter shell</span></td> </tr> <tr> <td align="left">TD-103/C</td><td align="left"><span class="Bold">Dome assembly with baffle plate</span></td> </tr> <tr> <td align="left">ON-104/C</td><td align="left"><span class="Bold">Inhalation piece</span></td> </tr> <tr> <td align="left">ON-105/C</td><td align="left"><span class="Bold">Mouthpiece</span></td> </tr> <tr> <td align="left">TD-118</td><td align="left"><span class="Bold">Water level cup</span></td> </tr> <tr> <td align="left">TD-153</td><td align="left"><span class="Bold">Carrying case</span></td> </tr> <tr class="Last"> <td align="left">TD-155</td><td align="left"><span class="Bold">Distilled water carrier</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\" valign=\"top\">Note: Part number subject to change.</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"left\">ON-110HPA</td><td align=\"left\"><span class=\"Bold\">Rechargeable battery</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-100Z</td><td align=\"left\"><span class=\"Bold\">12V DC adapter</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-100N-US</td><td align=\"left\"><span class=\"Bold\">AC wall plug</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-102/1/C</td><td align=\"left\"><span class=\"Bold\">Medicine cup, Quantity-16</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-109</td><td align=\"left\"><span class=\"Bold\">Filter membranes</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-120/C</td><td align=\"left\"><span class=\"Bold\">Plugs</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-101/C</td><td align=\"left\"><span class=\"Bold\">Filter shell</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-103/C</td><td align=\"left\"><span class=\"Bold\">Dome assembly with baffle plate</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-104/C</td><td align=\"left\"><span class=\"Bold\">Inhalation piece</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-105/C</td><td align=\"left\"><span class=\"Bold\">Mouthpiece</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-118</td><td align=\"left\"><span class=\"Bold\">Water level cup</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-153</td><td align=\"left\"><span class=\"Bold\">Carrying case</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">TD-155</td><td align=\"left\"><span class=\"Bold\">Distilled water carrier</span></td>\n</tr>\n</tbody>\n</table></div>" }

Glossary

{ "type": "p", "children": [], "text": "\nGlossary\n" }

Accessories: Parts of the TYVASO Inhalation System. See pages 6 and 7.

{ "type": "p", "children": [], "text": "\nAccessories: Parts of the TYVASO Inhalation System. See pages 6 and 7." }

Ampule: A sealed, lightweight clear plastic vial containing a 1-day supply of TYVASO® (treprostinil) Inhalation Solution.

{ "type": "p", "children": [], "text": "\nAmpule: A sealed, lightweight clear plastic vial containing a 1-day supply of TYVASO® (treprostinil) Inhalation Solution." }

Control light for inhalation: A green LED on the top surface of the inhalation device that signals when you should inhale.

{ "type": "p", "children": [], "text": "\nControl light for inhalation: A green LED on the top surface of the inhalation device that signals when you should inhale." }

Baffle plate: A blue plastic piece that is inside the dome assembly. The baffle plate helps turn TYVASO into particles that are the correct size to inhale.

{ "type": "p", "children": [], "text": "\nBaffle plate: A blue plastic piece that is inside the dome assembly. The baffle plate helps turn TYVASO into particles that are the correct size to inhale." }

Black ring: A round seal that fits on the bottom of the dome assembly. The seal helps ensure that TYVASO does not mix with the distilled water in the device chamber.

{ "type": "p", "children": [], "text": "\nBlack ring: A round seal that fits on the bottom of the dome assembly. The seal helps ensure that TYVASO does not mix with the distilled water in the device chamber." }

Display screen: A small area on the inhalation device that displays number and letter prompts to guide you through your treatment sessions.

{ "type": "p", "children": [], "text": "\nDisplay screen: A small area on the inhalation device that displays number and letter prompts to guide you through your treatment sessions." }

Distilled water: Water that is highly purified so that it contains only essential elements.

{ "type": "p", "children": [], "text": "\nDistilled water: Water that is highly purified so that it contains only essential elements." }

Dome assembly: The plastic accessory that contains the baffle plate and connects the mouthpiece, inhalation piece, and filter shells to the base of the inhalation device.

{ "type": "p", "children": [], "text": "\nDome assembly: The plastic accessory that contains the baffle plate and connects the mouthpiece, inhalation piece, and filter shells to the base of the inhalation device." }

Filter membrane: The white pad that goes into the filter shells.

{ "type": "p", "children": [], "text": "\nFilter membrane: The white pad that goes into the filter shells." }

Filter shells: Plastic accessories that hold the filter membranes.

{ "type": "p", "children": [], "text": "\nFilter shells: Plastic accessories that hold the filter membranes." }

Inhalation piece: The plastic accessory that connects the mouthpiece with the dome assembly.

{ "type": "p", "children": [], "text": "\nInhalation piece: The plastic accessory that connects the mouthpiece with the dome assembly." }

Inhalation device: The base of the TYVASO Inhalation System to which the accessories connect. The inhalation device contains the display screen and lights.

{ "type": "p", "children": [], "text": "\nInhalation device: The base of the TYVASO Inhalation System to which the accessories connect. The inhalation device contains the display screen and lights." }

Inhale: How you will breathe in TYVASO with the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nInhale: How you will breathe in TYVASO with the TYVASO Inhalation System." }

Medicine cup: The disposable plastic cone-shaped cup into which TYVASO is poured. The medicine cup fits inside the inhalation device chamber.

{ "type": "p", "children": [], "text": "\nMedicine cup: The disposable plastic cone-shaped cup into which TYVASO is poured. The medicine cup fits inside the inhalation device chamber." }

Mouthpiece: The plastic part that you will breathe through (using your mouth) to inhale TYVASO.

{ "type": "p", "children": [], "text": "\nMouthpiece: The plastic part that you will breathe through (using your mouth) to inhale TYVASO." }

ON/OFF button: A manually activated control on the front of the device that switches between fully on and fully off power states.

{ "type": "p", "children": [], "text": "\nON/OFF button: A manually activated control on the front of the device that switches between fully on and fully off power states." }

Plugs: Plastic accessories that are inserted into the openings of the dome assembly between treatment sessions. Plugs help keep TYVASO from spilling if the inhalation device tips over.

{ "type": "p", "children": [], "text": "\nPlugs: Plastic accessories that are inserted into the openings of the dome assembly between treatment sessions. Plugs help keep TYVASO from spilling if the inhalation device tips over." }

Prompts: The audio and visual signals that help guide you through the treatment sessions.

{ "type": "p", "children": [], "text": "\nPrompts: The audio and visual signals that help guide you through the treatment sessions." }

Sensor: The silver object on the inside wall of the device chamber. The sensor must be covered with distilled water for the TYVASO Inhalation System to function properly.

{ "type": "p", "children": [], "text": "\nSensor: The silver object on the inside wall of the device chamber. The sensor must be covered with distilled water for the TYVASO Inhalation System to function properly." }

Status light: A multicolored LED on the front of the inhalation device that indicates the device's operational status.

{ "type": "p", "children": [], "text": "\nStatus light: A multicolored LED on the front of the inhalation device that indicates the device's operational status." }

Start/Stop treatment button: A manually activated control on the front of the device that begins or pauses treatment.

{ "type": "p", "children": [], "text": "\nStart/Stop treatment button: A manually activated control on the front of the device that begins or pauses treatment." }

Specialty pharmacy provider: A pharmacy that carries only specialized medicines and medical devices. Your specialty pharmacy provider is a good source of information about TYVASO and the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nSpecialty pharmacy provider: A pharmacy that carries only specialized medicines and medical devices. Your specialty pharmacy provider is a good source of information about TYVASO and the TYVASO Inhalation System." }

Treatment session: One (1) of four (4) daily sessions during which you will take TYVASO with a specific number of inhalations.

{ "type": "p", "children": [], "text": "\nTreatment session: One (1) of four (4) daily sessions during which you will take TYVASO with a specific number of inhalations." }

TYVASO: The prescription medicine that you will use with the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nTYVASO: The prescription medicine that you will use with the TYVASO Inhalation System." }

Water chamber: The white hollow portion in the center of the inhalation device into which distilled water and the medicine cup are placed.

{ "type": "p", "children": [], "text": "\nWater chamber: The white hollow portion in the center of the inhalation device into which distilled water and the medicine cup are placed." }

Warranty Information

{ "type": "p", "children": [], "text": "\nWarranty Information\n" }

Your TYVASO Inhalation System is granted a full replacement or repair warranty good for two (2) years from your date of receipt of the TYVASO Inhalation System Starter Kit or five (5) years from the date of manufacture, whichever comes first. This warranty applies to the TYVASO Inhalation System device only. Accessory components are not covered under warranty.

{ "type": "p", "children": [], "text": "\nYour TYVASO Inhalation System is granted a full replacement or repair warranty good for two (2) years from your date of receipt of the TYVASO Inhalation System Starter Kit or five (5) years from the date of manufacture, whichever comes first. This warranty applies to the TYVASO Inhalation System device only. Accessory components are not covered under warranty.\n" }

Circumstances that may void your warranty include:

{ "type": "p", "children": [], "text": "\nCircumstances that may void your warranty include:\n" }

{ "type": "ul", "children": [ "Modification or disassembly of the TYVASO Inhalation System device by anyone other than a factory-authorized technician", "Failure to comply with the written Instructions for Use manual when operating the TYVASO Inhalation System", "Unapproved use of the TYVASO Inhalation System" ], "text": "" }

For all inquiries relating to service or warranty for your TYVASO Inhalation System, contact your specialty pharmacy provider. You should have the following information available:

{ "type": "p", "children": [], "text": "\nFor all inquiries relating to service or warranty for your TYVASO Inhalation System, contact your specialty pharmacy provider. You should have the following information available:\n" }

{ "type": "ul", "children": [ "Device serial number (located on bottom of TYVASO Inhalation System)", "Date TYVASO Inhalation System was acquired", "Nature of the problem and any steps taken to fix it" ], "text": "" }

Graphics in IFU are for representation only. Images may not be shown to scale

{ "type": "p", "children": [], "text": "\nGraphics in IFU are for representation only. Images may not be shown to scale\n" }

TYVASO® INHALATION SYSTEM Instructions for Use

{ "type": "p", "children": [], "text": "\nTYVASO®\n\nINHALATION SYSTEM\n\nInstructions for Use\n" }

TYVASO Inhalation Solution is for prescription use only.

{ "type": "p", "children": [], "text": "\nTYVASO Inhalation Solution is for prescription use only.\n" }

TYVASO is a registered trademark of United Therapeutics Corporation.

{ "type": "p", "children": [], "text": "TYVASO is a registered trademark of United Therapeutics Corporation." }

Literature Issued 2016-07-30

{ "type": "p", "children": [], "text": "Literature Issued 2016-07-30" }

For further questions and information, or to report an adverse reaction, please call 1-877-UNITHER (1-877-864-8437).

{ "type": "p", "children": [], "text": "\nFor further questions and information, or to report an adverse reaction, please call 1-877-UNITHER (1-877-864-8437).\n" }

Emergency contact information

{ "type": "p", "children": [], "text": "\nEmergency contact information\n" }

Clinician: ___________________________________

{ "type": "p", "children": [], "text": "Clinician: ___________________________________" }

Nurse educator: ______________________________

{ "type": "p", "children": [], "text": "Nurse educator: ______________________________" }

Specialty pharmacist: __________________________

{ "type": "p", "children": [], "text": "Specialty pharmacist: __________________________" }

United Therapeutics: ___________________________

{ "type": "p", "children": [], "text": "United Therapeutics: ___________________________" }

Distributed by: United Therapeutics CorporationResearch Triangle Park, North Carolina 27709

{ "type": "p", "children": [], "text": "\nDistributed by:\nUnited Therapeutics CorporationResearch Triangle Park, North Carolina 27709" }

TYVASO® (treprostinil) INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "\nTYVASO®\n\n(treprostinil)\n\nINHALATIONSOLUTION\n" }

© 2016, United Therapeutics Corporation. All rights reserved.RTP-1-00052 Rev. E

{ "type": "p", "children": [], "text": "© 2016, United Therapeutics Corporation. All rights reserved.RTP-1-00052 Rev. E" }

TYVASO® INHALATION SYSTEM

{ "type": "p", "children": [], "text": "\nTYVASO®\n\nINHALATION SYSTEM\n" }

Instructions for Use Manual

{ "type": "p", "children": [], "text": "\nInstructions for Use Manual\n" }

TYVASO® (treprostinil) INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "\nTYVASO®\n\n(treprostinil)\nINHALATIONSOLUTION\n" }

Contents

{ "type": "p", "children": [], "text": "\nContents\n" }

<div class="scrollingtable"><table class="Noautorules" width="60%"> <col align="left" valign="top" width="80%"/> <col align="right" valign="top" width="20%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">Overview of your TYVASO Inhalation System</span></td><td align="right"><span class="Bold">4</span></td> </tr> <tr> <td align="left">  Introduction</td><td align="right">6</td> </tr> <tr> <td align="left">  Safety and general instructions</td><td align="right">8</td> </tr> <tr> <td align="left">  Buttons, indicators, and markings</td><td align="right">10</td> </tr> <tr class="Botrule"> <td align="left">  Inhalation device display screens</td><td align="right">16</td> </tr> <tr> <td align="left" valign="bottom"><span class="Bold">Programming your TYVASO Inhalation System before use</span></td><td align="right" valign="bottom"><span class="Bold">18</span></td> </tr> <tr> <td align="left">  Charging device before use</td><td align="right">20</td> </tr> <tr> <td align="left">  Setting your prescribed dose</td><td align="right">22</td> </tr> <tr class="Botrule"> <td align="left">  Adjusting device's audio volume</td><td align="right">24</td> </tr> <tr> <td align="left"><span class="Bold">Preparing and using your TYVASO Inhalation System for daily treatments</span></td><td align="right"><span class="Bold">26</span></td> </tr> <tr> <td align="left">  Prepare a proper environment</td><td align="right">28</td> </tr> <tr> <td align="left">  Gather supplies</td><td align="right">29</td> </tr> <tr> <td align="left">  Fill water chamber and medicine cup</td><td align="right">32</td> </tr> <tr> <td align="left">  Assemble inhalation device</td><td align="right">35</td> </tr> <tr> <td align="left">  Power on inhalation device</td><td align="right">40</td> </tr> <tr class="Botrule"> <td align="left">  Inhale your medicine</td><td align="right">42</td> </tr> <tr> <td align="left"><span class="Bold">Cleaning and Storing your TYVASO Inhalation System</span></td><td align="right"><span class="Bold">46</span></td> </tr> <tr> <td align="left">  Storing between sessions during the day</td><td align="right">48</td> </tr> <tr> <td align="left">  End of day cleaning</td><td align="right">52</td> </tr> <tr> <td align="left">  Recharging the battery</td><td align="right">57</td> </tr> <tr> <td align="left">  Weekly cleaning</td><td align="right">59</td> </tr> <tr> <td align="left">  Monthly Refill Kit</td><td align="right">60</td> </tr> <tr class="Botrule"> <td align="left">  Replacing your devices</td><td align="right">61</td> </tr> <tr> <td align="left"><span class="Bold">Help / More information about your TYVASO Inhalation System</span></td><td align="right"><span class="Bold">62</span></td> </tr> <tr> <td align="left">  Troubleshooting</td><td align="right">64</td> </tr> <tr> <td align="left">  Specifications</td><td align="right">76</td> </tr> <tr> <td align="left">  Electromagnetic compatibility (EMC)</td><td align="right">79</td> </tr> <tr> <td align="left">  Glossary</td><td align="right">87</td> </tr> <tr class="Botrule"> <td align="left">  Warranty information</td><td align="right">90</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"60%\">\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<col align=\"right\" valign=\"top\" width=\"20%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">Overview of your TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">4</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Introduction</td><td align=\"right\">6</td>\n</tr>\n<tr>\n<td align=\"left\">  Safety and general instructions</td><td align=\"right\">8</td>\n</tr>\n<tr>\n<td align=\"left\">  Buttons, indicators, and markings</td><td align=\"right\">10</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  Inhalation device display screens</td><td align=\"right\">16</td>\n</tr>\n<tr>\n<td align=\"left\" valign=\"bottom\"><span class=\"Bold\">Programming your TYVASO Inhalation System before use</span></td><td align=\"right\" valign=\"bottom\"><span class=\"Bold\">18</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Charging device before use</td><td align=\"right\">20</td>\n</tr>\n<tr>\n<td align=\"left\">  Setting your prescribed dose</td><td align=\"right\">22</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  Adjusting device's audio volume</td><td align=\"right\">24</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Preparing and using your TYVASO Inhalation System for daily treatments</span></td><td align=\"right\"><span class=\"Bold\">26</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Prepare a proper environment</td><td align=\"right\">28</td>\n</tr>\n<tr>\n<td align=\"left\">  Gather supplies</td><td align=\"right\">29</td>\n</tr>\n<tr>\n<td align=\"left\">  Fill water chamber and medicine cup</td><td align=\"right\">32</td>\n</tr>\n<tr>\n<td align=\"left\">  Assemble inhalation device</td><td align=\"right\">35</td>\n</tr>\n<tr>\n<td align=\"left\">  Power on inhalation device</td><td align=\"right\">40</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  Inhale your medicine</td><td align=\"right\">42</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Cleaning and Storing your TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">46</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Storing between sessions during the day</td><td align=\"right\">48</td>\n</tr>\n<tr>\n<td align=\"left\">  End of day cleaning</td><td align=\"right\">52</td>\n</tr>\n<tr>\n<td align=\"left\">  Recharging the battery</td><td align=\"right\">57</td>\n</tr>\n<tr>\n<td align=\"left\">  Weekly cleaning</td><td align=\"right\">59</td>\n</tr>\n<tr>\n<td align=\"left\">  Monthly Refill Kit</td><td align=\"right\">60</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  Replacing your devices</td><td align=\"right\">61</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Help / More information about your TYVASO Inhalation System</span></td><td align=\"right\"><span class=\"Bold\">62</span></td>\n</tr>\n<tr>\n<td align=\"left\">  Troubleshooting</td><td align=\"right\">64</td>\n</tr>\n<tr>\n<td align=\"left\">  Specifications</td><td align=\"right\">76</td>\n</tr>\n<tr>\n<td align=\"left\">  Electromagnetic compatibility (EMC)</td><td align=\"right\">79</td>\n</tr>\n<tr>\n<td align=\"left\">  Glossary</td><td align=\"right\">87</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  Warranty information</td><td align=\"right\">90</td>\n</tr>\n</tbody>\n</table></div>" }

Overview of your TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nOverview of your TYVASO Inhalation System\n" }

Section overview

{ "type": "p", "children": [], "text": "\nSection overview\n" }

This section introduces you to your TYVASO Inhalation System and provides important safety information about using your system.

{ "type": "p", "children": [], "text": "This section introduces you to your TYVASO Inhalation System and provides important safety information about using your system." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">What you will need:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  ▶ A clean place to review these instructions</td> </tr> <tr class="Botrule"> <td align="left">  ▶ TYVASO Inhalation System to refer to while reading instructions</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">What you will need:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ A clean place to review these instructions</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ TYVASO Inhalation System to refer to while reading instructions</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="80%"/> <col align="right" valign="bottom" width="20%"/> <thead> <tr> <th align="left" colspan="2">What is covered in this section:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  A: Introduction</td><td align="right">6</td> </tr> <tr class="Botrule"> <td align="left">  B: Safety and general instructions</td><td align="right">8</td> </tr> <tr class="Botrule"> <td align="left">  C: Buttons, indicators, and markings</td><td align="right">10</td> </tr> <tr class="Botrule"> <td align="left">  D: Inhalation device display screens</td><td align="right">16</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"80%\"/>\n<col align=\"right\" valign=\"bottom\" width=\"20%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"2\">What is covered in this section:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  A: Introduction</td><td align=\"right\">6</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  B: Safety and general instructions</td><td align=\"right\">8</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  C: Buttons, indicators, and markings</td><td align=\"right\">10</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  D: Inhalation device display screens</td><td align=\"right\">16</td>\n</tr>\n</tbody>\n</table></div>" }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

Do not start treatment with TYVASO until you have been trained to use the TYVASO Inhalation System. Make sure you understand all of the directions. Always ask your doctor or specialty pharmacy provider if you have any questions or are unsure of anything you are taught.

{ "type": "p", "children": [], "text": "Do not start treatment with TYVASO until you have been trained to use the TYVASO Inhalation System. Make sure you understand all of the directions. Always ask your doctor or specialty pharmacy provider if you have any questions or are unsure of anything you are taught." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">A: Introduction</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">A: Introduction</span></td>\n</tr>\n</tbody>\n</table></div>" }

Your doctor has prescribed TYVASO® (treprostinil) Inhalation Solution. Please see the accompanying Patient Information for important safety information on TYVASO.

{ "type": "p", "children": [], "text": "Your doctor has prescribed TYVASO® (treprostinil) Inhalation Solution. Please see the accompanying Patient Information for important safety information on TYVASO." }

TYVASO is a prescription medicine used in adults to treat pulmonary arterial hypertension (PAH; WHO Group 1) and pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3), which are diseases causing high blood pressure in the arteries of your lungs. TYVASO can improve exercise ability. The effects decrease over 4 hours; treatment timing can be adjusted for planned activities.

{ "type": "p", "children": [], "text": "TYVASO is a prescription medicine used in adults to treat pulmonary arterial hypertension (PAH; WHO Group 1) and pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3), which are diseases causing high blood pressure in the arteries of your lungs. TYVASO can improve exercise ability. The effects decrease over 4 hours; treatment timing can be adjusted for planned activities." }

TYVASO is breathed in (inhaled) using the TYVASO Inhalation System, which consists of the inhalation device and its accessories.

{ "type": "p", "children": [], "text": "TYVASO is breathed in (inhaled) using the TYVASO Inhalation System, which consists of the inhalation device and its accessories." }

This Instructions for Use manual for the TYVASO Inhalation System provides important safety information. It is important that you read these instructions and the TYVASO Patient Information before setting up and using the TYVASO Inhalation System. If you have any questions, talk to your doctor or specialty pharmacy provider.

{ "type": "p", "children": [], "text": "This Instructions for Use manual for the TYVASO Inhalation System provides important safety information. It is important that you read these instructions and the TYVASO Patient Information before setting up and using the TYVASO Inhalation System. If you have any questions, talk to your doctor or specialty pharmacy provider." }

Before beginning treatment with TYVASO, you will receive either a Patient Starter Kit containing a 28-day supply of TYVASO or an Institutional Starter Kit containing a 4-day supply of medication.

{ "type": "p", "children": [], "text": "Before beginning treatment with TYVASO, you will receive either a Patient Starter Kit containing a 28-day supply of TYVASO or an Institutional Starter Kit containing a 4-day supply of medication." }

Both kits include 2 complete inhalation devices (all accessories and supplies included). When you refill your prescription for TYVASO each month, you will receive a Refill Kit that contains a 28-day supply of TYVASO and new accessories. You will receive replacement devices every 2 years from your date of receipt of the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "Both kits include 2 complete inhalation devices (all accessories and supplies included). When you refill your prescription for TYVASO each month, you will receive a Refill Kit that contains a 28-day supply of TYVASO and new accessories. You will receive replacement devices every 2 years from your date of receipt of the TYVASO Inhalation System." }

 CAUTION: Federal law restricts this device to sale by or on the order of a physician, or other licensed practitioner.

{ "type": "p", "children": [], "text": "\n CAUTION: Federal law restricts this device to sale by or on the order of a physician, or other licensed practitioner." }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

{ "type": "ul", "children": [ "Keep this Instructions for Use manual in a safe place where you can easily get to it for reference. For example, store the booklet in the TYVASO Inhalation System carrying case, along with your other supplies.", "TYVASO Inhalation System is intended solely for the delivery of TYVASO (treprostinil) Inhalation Solution. TYVASO is for administration only with the TYVASO Inhalation System." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">B: Safety and general instructions</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">B: Safety and general instructions</span></td>\n</tr>\n</tbody>\n</table></div>" }

The TYVASO Inhalation System should be handled carefully. Take the following precautions and follow all instructions in this document to avoid injury and ensure proper use:

{ "type": "p", "children": [], "text": "The TYVASO Inhalation System should be handled carefully. Take the following precautions and follow all instructions in this document to avoid injury and ensure proper use:" }

Delivering treatments:

{ "type": "p", "children": [], "text": "Delivering treatments:" }

{ "type": "ul", "children": [ "Read the instructions carefully and completely to prevent damage to your TYVASO Inhalation System and help you get the best results.", "This device should only be used on the order of your doctor or licensed healthcare practitioner.", "Conduct only the number of treatment sessions and inhalations you have been prescribed.", "Ensure the breath counter is correctly programmed prior to beginning a treatment (see page 22).", "Turn off the device when not in use.", "Do not use the device with an anesthetic breathing system or ventilator breathing system.", "Use only the supplies provided in the Starter Kit and Monthly Refill Kit for correct device function." ], "text": "" }

Handling the device:

{ "type": "p", "children": [], "text": "Handling the device:" }

{ "type": "ul", "children": [ "Do not peel or remove the labels from the device.", "Do not drop the device.", "The device does not include internal, replaceable parts. Do not attempt to open the device, modify the device, or remove device labeling." ], "text": "" }

Your environment:

{ "type": "p", "children": [], "text": "Your environment:" }

{ "type": "ul", "children": [ "Do not leave the device alone with a small child.", "Do not immerse the device in water or other liquids, or place in dishwasher.", "Do not place any system components in a microwave, conventional oven, or dishwasher.", "Do not use the device near flammable liquids and materials or heated surfaces.", "Do not place the device or use the device in the presence of strong electric or magnetic fields (e.g., microwave oven, magnetic imaging equipment).", "Wireless communications equipment (e.g., cell phone) can affect operation of the device and should be kept at least a distance of 3.3 meters (about 11 feet) away while using the device.", "If the device performance is affected by exposure to any conditions listed here, see the Troubleshooting section, or contact your healthcare provider or specialty pharmacy provider." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">C: Buttons, indicators, and markings</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">C: Buttons, indicators, and markings</span></td>\n</tr>\n</tbody>\n</table></div>" }

Inhalation device

{ "type": "p", "children": [], "text": "\nInhalation device\n" }

Inhalation indicator lights

{ "type": "p", "children": [], "text": "\nInhalation indicator lights\n" }

Lights on top of device flash green when you should inhale.

{ "type": "p", "children": [], "text": "Lights on top of device flash green when you should inhale." }

On/Off, Start/Pause (blue) button

{ "type": "p", "children": [], "text": "\n On/Off, Start/Pause (blue) button\n" }

Press and hold to power device on or off. Once device is on, press and immediately release (do not hold down) to start or pause treatment.

{ "type": "p", "children": [], "text": "Press and hold to power device on or off. Once device is on, press and immediately release (do not hold down) to start or pause treatment." }

Device Display

{ "type": "p", "children": [], "text": "\nDevice Display\n" }

Provides instructions and device information.

{ "type": "p", "children": [], "text": "Provides instructions and device information." }

Run / Program switch

{ "type": "p", "children": [], "text": "\nRun / Program switch\n" }

Slide up to Run mode when you are ready to deliver your dose. Slide down to Program mode to program the number of breaths for your dose.

{ "type": "p", "children": [], "text": "Slide up to Run mode when you are ready to deliver your dose. Slide down to Program mode to program the number of breaths for your dose." }

Volume / Breaths toggle button

{ "type": "p", "children": [], "text": "\nVolume / Breaths toggle button\n" }

When set to Run mode, push + to increase beeping volume, or push - to decrease beeping volume.

{ "type": "p", "children": [], "text": "When set to Run mode, push + to increase beeping volume, or push - to decrease beeping volume." }

When set to Program mode, push + to increase the number of breaths, or push - to decrease the number of breaths required for each dose.

{ "type": "p", "children": [], "text": "When set to Program mode, push + to increase the number of breaths, or push - to decrease the number of breaths required for each dose." }

Power status light

{ "type": "p", "children": [], "text": "\nPower status light\n" }

Lights green when power is connected and battery is charging.

{ "type": "p", "children": [], "text": "\n Lights green when power is connected and battery is charging." }

Power port

{ "type": "p", "children": [], "text": "\nPower port\n" }

Port for plugging into a power source using the AC wall plug.

{ "type": "p", "children": [], "text": "Port for plugging into a power source using the AC wall plug." }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="center" valign="middle" width="20%"/> <col align="left" valign="middle" width="80%"/> <thead> <tr> <th align="left" colspan="2">Additional device markings</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-108.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Manufacturer. Indicates the medical device manufacturer.<br/>(Symbol 5.1.1 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-109.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Equipment should not be disposed of in the trash.<br/>(Figure 1 of BS EN 50419:2006 - Marking of Electrical and Electronic Equipment in accordance with Article 11(2) of Directive 2002/96/EC (WEEE))</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-110.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Catalogue number. Indicates the manufacturer's catalogue number so that the medical device can be identified. (Symbol 5.1.6 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-111.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Serial number. Indicates the manufacturer's serial number so that a specific medical device can be identified. (Symbol 5.1.7 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-112.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Consult instructions for use. Please read the accompanying instructions and labels for important information regarding the TYVASO Inhalation System. (Symbol 5.4.3 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-113.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System has a Type BF Applied part. Type BF Applied parts comply with specific requirements to provide protection against shock and are not suitable for direct cardiac applications.<br/>(Symbol 5333 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-114.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System requires a 14V DC power supply. Use only the power supply intended for the TYVASO Inhalation System.<br/> (Direct Current, Symbol 5031 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-115.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System complies with the requirements of Protection Class II. Class II equipment provides additional precautions, over and above basic insulation, to provide protection against electric shock. (Class II equipment, Symbol 5172 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-116.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation Device provides level 2 solid particle protection and level 2 liquid ingress protection per IEC 60529 specifications.</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-117.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">The TYVASO Inhalation System should only be used on the order of your doctor or licensed healthcare provider. (Symbol statement as provided under 21 CFR 801.109(b)(1))</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-118.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Power stand by. Indicates the control for powering on and off the TYVASO Inhalation System. ("On" / "Off", Symbol 5010 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td> </tr> <tr class="Botrule"> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-119.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Start/Pause. Indicates the control for starting a treatment session once the device is powered on, and for pausing a treatment once a treatment session has started. (Play and Pause, Symbols 5107B and 5111B, respectively, of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"center\" valign=\"middle\" width=\"20%\"/>\n<col align=\"left\" valign=\"middle\" width=\"80%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"2\">Additional device markings</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-108.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Manufacturer. Indicates the medical device manufacturer.<br/>(Symbol 5.1.1 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-109.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Equipment should not be disposed of in the trash.<br/>(Figure 1 of BS EN 50419:2006 - Marking of Electrical and Electronic Equipment in accordance with Article 11(2) of Directive 2002/96/EC (WEEE))</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-110.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Catalogue number. Indicates the manufacturer's catalogue number so that the medical device can be identified. (Symbol 5.1.6 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-111.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Serial number. Indicates the manufacturer's serial number so that a specific medical device can be identified. (Symbol 5.1.7 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-112.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Consult instructions for use. Please read the accompanying instructions and labels for important information regarding the TYVASO Inhalation System. (Symbol 5.4.3 of ANSI/AAMI/ISO 15223-1: 2012 Medical devices - symbols to be used with medical devices labels, labeling, and information to be supplied - part 1: general requirements)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-113.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System has a Type BF Applied part. Type BF Applied parts comply with specific requirements to provide protection against shock and are not suitable for direct cardiac applications.<br/>(Symbol 5333 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-114.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System requires a 14V DC power supply. Use only the power supply intended for the TYVASO Inhalation System.<br/> (Direct Current, Symbol 5031 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-115.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System complies with the requirements of Protection Class II. Class II equipment provides additional precautions, over and above basic insulation, to provide protection against electric shock. (Class II equipment, Symbol 5172 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-116.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation Device provides level 2 solid particle protection and level 2 liquid ingress protection per IEC 60529 specifications.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-117.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">The TYVASO Inhalation System should only be used on the order of your doctor or licensed healthcare provider. (Symbol statement as provided under 21 CFR 801.109(b)(1))</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-118.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Power stand by. Indicates the control for powering on and off the TYVASO Inhalation System. (\"On\" / \"Off\", Symbol 5010 of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-119.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Start/Pause. Indicates the control for starting a treatment session once the device is powered on, and for pausing a treatment once a treatment session has started. (Play and Pause, Symbols 5107B and 5111B, respectively, of IEC 60417 Database Snapshot - Graphical symbols for use on equipment)</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <thead> <tr class="Botrule"> <th align="left" colspan="4">D: Inhalation device display screens</th> </tr> </thead> <tbody> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-120.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Lrule Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-121.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-122.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-123.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center"><span class="Bold">Splash screen</span> <br/>Device name and software version</td><td align="center" class="Lrule Rrule"><span class="Bold">Last Treatment</span> <br/>Time since your last treatment</td><td align="center" class="Rrule"><span class="Bold">Program Breaths</span> <br/>Number of breaths set in Program mode</td><td align="center"><span class="Bold">Adjust Volume</span> <br/>Audio volume level set in Run mode</td> </tr> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-124.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Lrule Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-125.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-126.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-127.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center"><span class="Bold">Breaths Left</span> <br/>Number of breaths left in a current dose</td><td align="center" class="Lrule Rrule"><span class="Bold">Exhale</span> <br/>Prompt to exhale during a dose</td><td align="center" class="Rrule"><span class="Bold">Inhale</span> <br/>Prompt to inhale during a dose</td><td align="center"><span class="Bold">Done</span> <br/>Treatment session is complete</td> </tr> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-128.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Lrule Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-129.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" colspan="2" rowspan="3"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-130.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center"><span class="Bold">Pause</span> <br/>You have paused a treatment session</td><td align="center" class="Lrule Rrule"><span class="Bold">Call Support</span> <br/>Device is not working, call your specialty pharmacy provider for support</td> </tr> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-131.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Lrule Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-132.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center"><span class="Bold">Add Water</span> <br/>Wrong or missing fluid in water chamber</td><td align="center" class="Lrule Rrule"><span class="Bold">Charge Battery</span> <br/>Battery not charged enough to deliver treatment</td><td align="center"><span class="Bold">Status icons</span> <br/>Icons that might appear at bottom of the screen</td><td align="center"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<thead>\n<tr class=\"Botrule\">\n<th align=\"left\" colspan=\"4\">D: Inhalation device display screens</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-120.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Lrule Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-121.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-122.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-123.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\"><span class=\"Bold\">Splash screen</span>\n<br/>Device name and software version</td><td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">Last Treatment</span>\n<br/>Time since your last treatment</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Program Breaths</span>\n<br/>Number of breaths set in Program mode</td><td align=\"center\"><span class=\"Bold\">Adjust Volume</span>\n<br/>Audio volume level set in Run mode</td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-124.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Lrule Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-125.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-126.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-127.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\"><span class=\"Bold\">Breaths Left</span>\n<br/>Number of breaths left in a current dose</td><td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">Exhale</span>\n<br/>Prompt to exhale during a dose</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Inhale</span>\n<br/>Prompt to inhale during a dose</td><td align=\"center\"><span class=\"Bold\">Done</span>\n<br/>Treatment session is complete</td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-128.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Lrule Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-129.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" colspan=\"2\" rowspan=\"3\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-130.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\"><span class=\"Bold\">Pause</span>\n<br/>You have paused a treatment session</td><td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">Call Support</span>\n<br/>Device is not working, call your specialty pharmacy provider for support</td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-131.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Lrule Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-132.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\"><span class=\"Bold\">Add Water</span>\n<br/>Wrong or missing fluid in water chamber</td><td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">Charge Battery</span>\n<br/>Battery not charged enough to deliver treatment</td><td align=\"center\"><span class=\"Bold\">Status icons</span>\n<br/>Icons that might appear at bottom of the screen</td><td align=\"center\"></td>\n</tr>\n</tbody>\n</table></div>" }

Programming your TYVASO Inhalation System before use

{ "type": "p", "children": [], "text": "\nProgramming your TYVASO Inhalation System before use\n" }

Section overview

{ "type": "p", "children": [], "text": "\nSection overview\n" }

This section provides instructions for charging your device, setting your dose, and adjusting the device's audio volume before you use the device for a treatment.

{ "type": "p", "children": [], "text": "This section provides instructions for charging your device, setting your dose, and adjusting the device's audio volume before you use the device for a treatment." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">What you will need:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  ▶ A clean place to work with the device</td> </tr> <tr class="Botrule"> <td align="left">  ▶ TYVASO Inhalation Device</td> </tr> <tr class="Botrule"> <td align="left">  ▶ The number of breaths your doctor prescribed for each dose</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">What you will need:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ A clean place to work with the device</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ TYVASO Inhalation Device</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ The number of breaths your doctor prescribed for each dose</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="80%"/> <col align="right" valign="bottom" width="20%"/> <thead> <tr> <th align="left" colspan="2">What is covered in this section:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  A: Charging device before use</td><td align="right">20</td> </tr> <tr class="Botrule"> <td align="left">  B: Setting your prescribed dose</td><td align="right">22</td> </tr> <tr class="Botrule"> <td align="left">  C: Adjusting device's audio volume</td><td align="right">24</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"80%\"/>\n<col align=\"right\" valign=\"bottom\" width=\"20%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"2\">What is covered in this section:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  A: Charging device before use</td><td align=\"right\">20</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  B: Setting your prescribed dose</td><td align=\"right\">22</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  C: Adjusting device's audio volume</td><td align=\"right\">24</td>\n</tr>\n</tbody>\n</table></div>" }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

Do not start treatment with TYVASO until you have been trained to use the TYVASO Inhalation System. Make sure you understand all of the directions. Always ask your doctor or specialty pharmacy provider if you have any questions or are unsure of anything you are taught.

{ "type": "p", "children": [], "text": "Do not start treatment with TYVASO until you have been trained to use the TYVASO Inhalation System. Make sure you understand all of the directions. Always ask your doctor or specialty pharmacy provider if you have any questions or are unsure of anything you are taught." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">A: Charging device before use</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">A: Charging device before use</span></td>\n</tr>\n</tbody>\n</table></div>" }

1. Plug in device

{ "type": "p", "children": [], "text": "\n1. Plug in device\n" }

Important: A new device might not be fully charged when you receive it. Always charge the device before you first use it. You can also charge the device overnight, when not in use and in between uses.

{ "type": "p", "children": [], "text": "\nImportant: A new device might not be fully charged when you receive it. Always charge the device before you first use it. You can also charge the device overnight, when not in use and in between uses." }

Plug the AC wall plug's white connector into the port on the back of the inhalation device. Then, plug the AC wall plug into the wall outlet.

{ "type": "p", "children": [], "text": "Plug the AC wall plug's white connector into the port on the back of the inhalation device. Then, plug the AC wall plug into the wall outlet." }

The power status light above the port will light green when properly plugged in.

{ "type": "p", "children": [], "text": "The power status light above the port will light green when properly plugged in." }

2. Check the battery's status

{ "type": "p", "children": [], "text": "\n2. Check the battery's status\n" }

Make sure the Run / Program switch is set to Run. Press and hold the blue button to power on the device.

{ "type": "p", "children": [], "text": "Make sure the Run / Program switch is set to Run. Press and hold the blue button to power on the device." }

The battery icon at the bottom of the screen indicates battery status.

{ "type": "p", "children": [], "text": "The battery icon at the bottom of the screen indicates battery status." }

When you are done checking the battery status, press and hold the On/Off button until the display screen shuts off (note: letting the button go before the screen shuts off will start a treatment session).

{ "type": "p", "children": [], "text": "When you are done checking the battery status, press and hold the On/Off button until the display screen shuts off (note: letting the button go before the screen shuts off will start a treatment session)." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="top" width="50%"/> <col align="center" valign="middle" width="50%"/> <tbody class="Headless"> <tr> <td align="left">If there is not enough charge to conduct a treatment session, "Charge battery" appears on screen.</td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-132.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<col align=\"center\" valign=\"middle\" width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">If there is not enough charge to conduct a treatment session, \"Charge battery\" appears on screen.</td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-132.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">B: Setting your prescribed dose</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">B: Setting your prescribed dose</span></td>\n</tr>\n</tbody>\n</table></div>" }

Your doctor will prescribe the number of breaths you should take in each treatment session. You should program this number into the inhalation device before you use the device.

{ "type": "p", "children": [], "text": "Your doctor will prescribe the number of breaths you should take in each treatment session. You should program this number into the inhalation device before you use the device." }

1. Switch to Program

{ "type": "p", "children": [], "text": "\n1. Switch to Program\n" }

Slide the Run / Program switch on the side of the device down to Program mode. In Program mode you enter the prescribed number of breaths for each dose. You cannot begin a treatment in Program mode.

{ "type": "p", "children": [], "text": "Slide the Run / Program switch on the side of the device down to Program mode. In Program mode you enter the prescribed number of breaths for each dose. You cannot begin a treatment in Program mode." }

2. Power on

{ "type": "p", "children": [], "text": "\n2. Power on\n" }

Press and hold the On/Off button until the display screen turns on. The Program Breaths screen appears. The number of breaths currently set for each treatment session will flash.

{ "type": "p", "children": [], "text": "Press and hold the On/Off button until the display screen turns on. The Program Breaths screen appears. The number of breaths currently set for each treatment session will flash." }

3. Set breaths

{ "type": "p", "children": [], "text": "\n3. Set breaths\n" }

Use the Volume / Breaths toggle button to enter your prescribed number of breaths onto the program screen.

{ "type": "p", "children": [], "text": "Use the Volume / Breaths toggle button to enter your prescribed number of breaths onto the program screen." }

4. Switch to Run

{ "type": "p", "children": [], "text": "\n4. Switch to Run\n" }

Slide the Run / Program switch up to Run mode. Make sure your new breath count appears on screen.

{ "type": "p", "children": [], "text": "Slide the Run / Program switch up to Run mode. Make sure your new breath count appears on screen." }

5. Power off

{ "type": "p", "children": [], "text": "\n5. Power off\n" }

Press and hold the On/Off button until the display screen shuts off (note: letting the button go before the screen shuts off will start a treatment session).

{ "type": "p", "children": [], "text": "Press and hold the On/Off button until the display screen shuts off (note: letting the button go before the screen shuts off will start a treatment session)." }

Note: You will not need to program the breath count again, unless your prescribed number of breaths changes.

{ "type": "p", "children": [], "text": "Note: You will not need to program the breath count again, unless your prescribed number of breaths changes." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">C: Adjusting device's audio volume</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">C: Adjusting device's audio volume</span></td>\n</tr>\n</tbody>\n</table></div>" }

You can use the Volume / Breaths toggle button to adjust the volume of the audible signals (beeps) that the device provides as feedback during treatment sessions.

{ "type": "p", "children": [], "text": "You can use the Volume / Breaths toggle button to adjust the volume of the audible signals (beeps) that the device provides as feedback during treatment sessions." }

1. Switch to Run

{ "type": "p", "children": [], "text": "\n1. Switch to Run\n" }

Slide the Run / Program switch up to Run mode, if it is not in this position already.

{ "type": "p", "children": [], "text": "Slide the Run / Program switch up to Run mode, if it is not in this position already." }

2. Power on

{ "type": "p", "children": [], "text": "\n2. Power on\n" }

Press and hold the On/Off button until the display screen turns on, if it is not already turned on. The programmed number of breaths will appear with the words "Breaths left" and the battery icon at the bottom.

{ "type": "p", "children": [], "text": "Press and hold the On/Off button until the display screen turns on, if it is not already turned on. The programmed number of breaths will appear with the words \"Breaths left\" and the battery icon at the bottom." }

3. Adjust volume

{ "type": "p", "children": [], "text": "\n3. Adjust volume\n" }

With the Run / Program switch in the Run position, press the Volume / Breaths toggle button to access the Adjust Volume screen. Push + on the Volume / Breaths toggle button to increase beeping volume, or push - to decrease beeping volume.

{ "type": "p", "children": [], "text": "With the Run / Program switch in the Run position, press the Volume / Breaths toggle button to access the Adjust Volume screen. Push + on the Volume / Breaths toggle button to increase beeping volume, or push - to decrease beeping volume." }

<div class="scrollingtable"><table class="Noautorules" width="85%"> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="33%"/> <col align="center" valign="middle" width="34%"/> <tbody class="Headless"> <tr> <td align="center" colspan="3"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-142.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="right"> <p class="First"> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-143.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></p> </td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-144.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left"> <p class="First"> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-145.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></p> </td> </tr> <tr> <td align="right">audio off      </td><td align="center">mid-level volume</td><td align="left">maximum volume</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"85%\">\n<col align=\"center\" valign=\"middle\" width=\"33%\"/>\n<col align=\"center\" valign=\"middle\" width=\"33%\"/>\n<col align=\"center\" valign=\"middle\" width=\"34%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" colspan=\"3\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-142.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"right\">\n<p class=\"First\">\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-143.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></p>\n</td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-144.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">\n<p class=\"First\">\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-145.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></p>\n</td>\n</tr>\n<tr>\n<td align=\"right\">audio off      </td><td align=\"center\">mid-level volume</td><td align=\"left\">maximum volume</td>\n</tr>\n</tbody>\n</table></div>" }

4. Power off

{ "type": "p", "children": [], "text": "\n4. Power off\n" }

After adjusting the beeping volume up or down, the screen will display your new setting for a couple of seconds then return to the screen displaying the breaths left.

{ "type": "p", "children": [], "text": "After adjusting the beeping volume up or down, the screen will display your new setting for a couple of seconds then return to the screen displaying the breaths left." }

Press and hold the On/Off button until the display screen shuts off (note: letting the button go before the screen shuts off will start a treatment session).

{ "type": "p", "children": [], "text": "Press and hold the On/Off button until the display screen shuts off (note: letting the button go before the screen shuts off will start a treatment session)." }

Preparing and using your TYVASO Inhalation System for daily treatments

{ "type": "p", "children": [], "text": "Preparing and using your TYVASO Inhalation System for daily treatments" }

Section overview

{ "type": "p", "children": [], "text": "Section overview" }

This section provides instructions for preparing and using your TYVASO Inhalation System for daily treatments.

{ "type": "p", "children": [], "text": "This section provides instructions for preparing and using your TYVASO Inhalation System for daily treatments." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">What you will need:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">▶ A clean place to take your medicine</td> </tr> <tr class="Botrule"> <td align="left">▶ TYVASO Inhalation device</td> </tr> <tr class="Botrule"> <td align="left">▶ TYVASO Inhalation supplies</td> </tr> <tr> <td align="left" class="Botrule">▶ One ampule of TYVASO Inhalation Solution</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">What you will need:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ A clean place to take your medicine</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ TYVASO Inhalation device</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ TYVASO Inhalation supplies</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">▶ One ampule of TYVASO Inhalation Solution</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="80%"/> <col align="right" valign="bottom" width="20%"/> <thead> <tr> <th align="left" colspan="2">What is covered in this section:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  A: Prepare a proper environment</td><td align="right">28</td> </tr> <tr class="Botrule"> <td align="left">  B: Gather supplies</td><td align="right">29</td> </tr> <tr class="Botrule"> <td align="left">  C: Fill water chamber and medicine cup</td><td align="right">32</td> </tr> <tr class="Botrule"> <td align="left">  D: Assemble inhalation device</td><td align="right">35</td> </tr> <tr class="Botrule"> <td align="left">  E: Power on inhalation device</td><td align="right">40</td> </tr> <tr class="Botrule"> <td align="left">  F: Inhale your medicine</td><td align="right">42</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"80%\"/>\n<col align=\"right\" valign=\"bottom\" width=\"20%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"2\">What is covered in this section:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  A: Prepare a proper environment</td><td align=\"right\">28</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  B: Gather supplies</td><td align=\"right\">29</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  C: Fill water chamber and medicine cup</td><td align=\"right\">32</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  D: Assemble inhalation device</td><td align=\"right\">35</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  E: Power on inhalation device</td><td align=\"right\">40</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  F: Inhale your medicine</td><td align=\"right\">42</td>\n</tr>\n</tbody>\n</table></div>" }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

Before using the TYVASO Inhalation System, you should:

{ "type": "p", "children": [], "text": "Before using the TYVASO Inhalation System, you should:" }

{ "type": "ul", "children": [ "Wash your hands.", "Make sure the device is resting on a stable, flat surface during assembly.\n\n\n" ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">A: Prepare a proper environment</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">A: Prepare a proper environment</span></td>\n</tr>\n</tbody>\n</table></div>" }

Follow these important instructions before setting up your treatment:

{ "type": "p", "children": [], "text": "Follow these important instructions before setting up your treatment:" }

{ "type": "ul", "children": [ "Use the device in a quiet, distraction-free area.", "Try to use the device at times when your treatment will not be interrupted. If needed, you can pause your treatment (see page 44).", "Use the device in a comfortable space where you can stand or sit in an upright position.", "Use the device in an area where you can access a power source if you need to use the AC wall plug.", "The TYVASO Inhalation System is recommended for use indoors.", "Use the device in an area that provides enough space for the TYVASO Inhalation System and its accessories.", "Gather all necessary supplies on a stable, flat surface for assembly (see page 29 for list of supplies).", "Store the inhalation device at 15°C to 30°C (59°F to 86°F). Use at 15°C to 25°C (59°F to 77°F).", "Use the device in a well-lit area where you can clearly read these instructions, labels on the device, and the device screen." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">B: Gather supplies</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">B: Gather supplies</span></td>\n</tr>\n</tbody>\n</table></div>" }

Gather the following supplies before starting treatment. Use only the supplies provided in the starter kit and monthly refill kit for correct device function. Prior to use, inspect each part and do not use parts if they appear damaged or dirty.

{ "type": "p", "children": [], "text": "Gather the following supplies before starting treatment. Use only the supplies provided in the starter kit and monthly refill kit for correct device function. Prior to use, inspect each part and do not use parts if they appear damaged or dirty." }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="center" valign="top" width="33%"/> <col align="center" valign="top" width="33%"/> <col align="center" valign="top" width="34%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-5" name="footnote-5">*</a> </dt> <dd>These accessories are replaced every month. Replacement accessories are included in the Monthly Refill Kit.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr> <td align="center" colspan="2"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-148.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="middle"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-149.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center"><span class="Bold">Inhalation device</span> <br/>Powered off</td><td align="center"><span class="Bold">TYVASO ampules</span> <br/>Use 1 ampule per day</td><td align="center"><span class="Bold">Water level cup</span> <br/>with 45 mL of distilled water</td> </tr> <tr> <td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-150.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-151.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-152.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center" class="Rrule"><span class="Bold">Filter membranes<a class="Sup" href="#footnote-5" name="footnote-reference-5">*</a></span> <br/>Use 2 per day</td><td align="center" class="Rrule"><span class="Bold">Medicine cups<a class="Sup" href="#footnote-5">*</a></span> <br/>Use 1 per day</td><td align="center"><span class="Bold">Dome assembly<a class="Sup" href="#footnote-5">*</a></span></td> </tr> <tr> <td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-153.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-154.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-155.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center" class="Rrule"><span class="Bold">Mouthpiece<a class="Sup" href="#footnote-5">*</a></span></td><td align="center" class="Rrule"><span class="Bold">Inhalation piece<a class="Sup" href="#footnote-5">*</a></span></td><td align="center"><span class="Bold">2 filter shells<a class="Sup" href="#footnote-5">*</a></span></td> </tr> <tr> <td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-156.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-157.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" valign="bottom"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-158.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center" class="Rrule"><span class="Bold">2 Plugs<a class="Sup" href="#footnote-5">*</a></span> <br/>(Used when storing the device)</td><td align="center" class="Rrule"><span class="Bold">Carrying case</span></td><td align="center"><span class="Bold">Pen or pencil</span> (not provided) to record your treatment</td> </tr> <tr> <td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-159.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" class="Rrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-160.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-161.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center" class="Rrule"><span class="Bold">Distilled water carrier</span></td><td align="center" class="Rrule"><span class="Bold">AC wall plug</span></td><td align="center"><span class="Bold">Treatment Tracker Example</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"center\" valign=\"top\" width=\"33%\"/>\n<col align=\"center\" valign=\"top\" width=\"33%\"/>\n<col align=\"center\" valign=\"top\" width=\"34%\"/>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"3\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-5\" name=\"footnote-5\">*</a>\n</dt>\n<dd>These accessories are replaced every month. Replacement accessories are included in the Monthly Refill Kit.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" colspan=\"2\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-148.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"middle\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-149.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\"><span class=\"Bold\">Inhalation device</span>\n<br/>Powered off</td><td align=\"center\"><span class=\"Bold\">TYVASO ampules</span>\n<br/>Use 1 ampule per day</td><td align=\"center\"><span class=\"Bold\">Water level cup</span>\n<br/>with 45 mL of distilled water</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-150.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-151.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-152.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Filter membranes<a class=\"Sup\" href=\"#footnote-5\" name=\"footnote-reference-5\">*</a></span>\n<br/>Use 2 per day</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Medicine cups<a class=\"Sup\" href=\"#footnote-5\">*</a></span>\n<br/>Use 1 per day</td><td align=\"center\"><span class=\"Bold\">Dome assembly<a class=\"Sup\" href=\"#footnote-5\">*</a></span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-153.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-154.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-155.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Mouthpiece<a class=\"Sup\" href=\"#footnote-5\">*</a></span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Inhalation piece<a class=\"Sup\" href=\"#footnote-5\">*</a></span></td><td align=\"center\"><span class=\"Bold\">2 filter shells<a class=\"Sup\" href=\"#footnote-5\">*</a></span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-156.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-157.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" valign=\"bottom\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-158.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><span class=\"Bold\">2 Plugs<a class=\"Sup\" href=\"#footnote-5\">*</a></span>\n<br/>(Used when storing the device)</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Carrying case</span></td><td align=\"center\"><span class=\"Bold\">Pen or pencil</span> (not provided) to record your treatment</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-159.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" class=\"Rrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-160.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-161.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Distilled water carrier</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">AC wall plug</span></td><td align=\"center\"><span class=\"Bold\">Treatment Tracker Example</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">C: Fill water chamber and medicine cup</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">C: Fill water chamber and medicine cup</span></td>\n</tr>\n</tbody>\n</table></div>" }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

{ "type": "ul", "children": [ "\nWash your hands\n\n\n\n", "\nUnplug device when filling to avoid damage to cords or connectors.", "\nOnly use distilled water in the device. Distilled water is highly purified water that is required for the device to function properly. If you use another type of water (such as bottled or tap water), the device might not function properly. You can purchase distilled water at most grocery stores and pharmacies." ], "text": "" }

1. Fill water chamber

{ "type": "p", "children": [], "text": "\n1. Fill water chamber\n" }

Fill the water level cup with distilled water up to the arrow markers on the water cup. Use fresh distilled water each day (i.e., do not use water left in the water chamber from the previous day). Pour the distilled water into the water chamber.

{ "type": "p", "children": [], "text": "Fill the water level cup with distilled water up to the arrow markers on the water cup. Use fresh distilled water each day (i.e., do not use water left in the water chamber from the previous day). Pour the distilled water into the water chamber." }

Make sure the water level is above the upper, silver sensor and below the blue ring in the water chamber (about 45 mL of distilled water).

{ "type": "p", "children": [], "text": "Make sure the water level is above the upper, silver sensor and below the blue ring in the water chamber (about 45 mL of distilled water)." }

Do not overfill the water chamber, or else the medicine cup might not fit correctly.

{ "type": "p", "children": [], "text": "Do not overfill the water chamber, or else the medicine cup might not fit correctly." }

2. Place medicine cup

{ "type": "p", "children": [], "text": "\n2. Place medicine cup\n" }

Obtain 1 new medicine cup and inspect it. Do not use a medicine cup that is damaged (e.g., cracked or contains holes or dents), dirty, or was used before.

{ "type": "p", "children": [], "text": "Obtain 1 new medicine cup and inspect it. Do not use a medicine cup that is damaged (e.g., cracked or contains holes or dents), dirty, or was used before." }

Place the empty medicine cup into the water chamber of the device, making sure that the cup's bottom tip is in the distilled water.

{ "type": "p", "children": [], "text": "Place the empty medicine cup into the water chamber of the device, making sure that the cup's bottom tip is in the distilled water." }

 CAUTION: Make sure you place only 1 medicine cup. Placing multiple cups will prevent the flow of medicine.

{ "type": "p", "children": [], "text": "\n CAUTION: Make sure you place only 1 medicine cup. Placing multiple cups will prevent the flow of medicine." }

3. Gather one ampule

{ "type": "p", "children": [], "text": "\n3. Gather one ampule\n" }

Carefully cut open the top of the foil pouch, making sure not to cut the ampules. Each pouch contains 4 ampules. Remove 1 ampule of TYVASO.

{ "type": "p", "children": [], "text": "Carefully cut open the top of the foil pouch, making sure not to cut the ampules. Each pouch contains 4 ampules. Remove 1 ampule of TYVASO." }

Keep unused ampules in the foil pouch because the TYVASO medicine is sensitive to light. Write the date you first opened the pouch on the foil pouch.

{ "type": "p", "children": [], "text": "Keep unused ampules in the foil pouch because the TYVASO medicine is sensitive to light. Write the date you first opened the pouch on the foil pouch." }

One ampule contains enough medicine for 1 day of treatment no matter how many breaths your doctor has prescribed.

{ "type": "p", "children": [], "text": "One ampule contains enough medicine for 1 day of treatment no matter how many breaths your doctor has prescribed." }

 CAUTION: Ampules must be used within 7 days of opening foil pouch. Open only 1 pouch at a time. Throw away (discard) any unused ampules after 7 days.

{ "type": "p", "children": [], "text": "\n CAUTION: Ampules must be used within 7 days of opening foil pouch. Open only 1 pouch at a time. Throw away (discard) any unused ampules after 7 days." }

4. Open ampule

{ "type": "p", "children": [], "text": "\n4. Open ampule\n" }

Gently hold the ampule in the upright (top up) position and twist off its top.

{ "type": "p", "children": [], "text": "Gently hold the ampule in the upright (top up) position and twist off its top." }

 CAUTION: If any medicine from the ampule spills on your hands, wash your hands right away. Medicine contact with the skin can cause irritation.

{ "type": "p", "children": [], "text": "\n CAUTION: If any medicine from the ampule spills on your hands, wash your hands right away. Medicine contact with the skin can cause irritation." }

5. Squeeze ampule

{ "type": "p", "children": [], "text": "\n5. Squeeze ampule\n" }

Point the ampule straight down toward the medicine cup's center to avoid spills.

{ "type": "p", "children": [], "text": "Point the ampule straight down toward the medicine cup's center to avoid spills." }

Gently squeeze the medicine out of the ampule into the medicine cup. Squeeze until it is empty. Check to see that all of the medicine is in the medicine cup.

{ "type": "p", "children": [], "text": "Gently squeeze the medicine out of the ampule into the medicine cup. Squeeze until it is empty. Check to see that all of the medicine is in the medicine cup." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">D: Assemble inhalation device</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">D: Assemble inhalation device</span></td>\n</tr>\n</tbody>\n</table></div>" }

Important: Do not force parts together.

{ "type": "p", "children": [], "text": "\nImportant: Do not force parts together." }

The TYVASO Inhalation System is designed so the parts only fit together properly one way. When the device is assembled correctly, the parts should fit together easily.

{ "type": "p", "children": [], "text": "The TYVASO Inhalation System is designed so the parts only fit together properly one way. When the device is assembled correctly, the parts should fit together easily." }

1. Check dome assembly

{ "type": "p", "children": [], "text": "\n1. Check dome assembly\n" }

Visually check to make sure the black ring is securely placed in the dome assembly. The black ring should look like it does in the pictures below.

{ "type": "p", "children": [], "text": "Visually check to make sure the black ring is securely placed in the dome assembly. The black ring should look like it does in the pictures below." }

If the black ring is loose or missing, do not use the dome assembly. Throw it away and get a new one. If you need to order a new dome assembly, contact your specialty pharmacy provider.

{ "type": "p", "children": [], "text": "If the black ring is loose or missing, do not use the dome assembly. Throw it away and get a new one. If you need to order a new dome assembly, contact your specialty pharmacy provider." }

2. Attach dome assembly

{ "type": "p", "children": [], "text": "\n2. Attach dome assembly\n" }

Align the raised circle on the side of the dome assembly with the raised circle on the side of the device.

{ "type": "p", "children": [], "text": "Align the raised circle on the side of the dome assembly with the raised circle on the side of the device." }

Push down and screw the dome assembly onto the device clockwise (right) until the filter shell port is tight and pointed to the back of the device. You will hear clicks (or a slight crunching sound) as the dome assembly presses down on the medicine cup.

{ "type": "p", "children": [], "text": "Push down and screw the dome assembly onto the device clockwise (right) until the filter shell port is tight and pointed to the back of the device. You will hear clicks (or a slight crunching sound) as the dome assembly presses down on the medicine cup." }

Important: The dome assembly "clicks" only the first time it connects to the medicine cup. If you then realign the dome assembly you will not hear another click.

{ "type": "p", "children": [], "text": "\nImportant: The dome assembly \"clicks\" only the first time it connects to the medicine cup. If you then realign the dome assembly you will not hear another click." }

3. Install new filter membrane

{ "type": "p", "children": [], "text": "\n3. Install new filter membrane\n" }

Each day you will need to use a new filter membrane in each filter shell.

{ "type": "p", "children": [], "text": "Each day you will need to use a new filter membrane in each filter shell." }

Note: New filter shells come with fresh filter membranes already installed.

{ "type": "p", "children": [], "text": "Note: New filter shells come with fresh filter membranes already installed." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr> <td align="left">To install a new filter membrane:</td> </tr> <tr class="Botrule"> <td align="left">▶ a. Open the filter shell by unscrewing the 2 halves.</td> </tr> <tr class="Botrule"> <td align="left">▶ b. Place a new filter membrane in 1 of the filter shell halves.</td> </tr> <tr class="Botrule"> <td align="left">▶ c. Close the filter shell by screwing the 2 halves together until you can twist no further.</td> </tr> <tr class="Botrule"> <td align="left">▶ d. Repeat steps a-c for second filter shell.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">To install a new filter membrane:</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ a. Open the filter shell by unscrewing the 2 halves.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ b. Place a new filter membrane in 1 of the filter shell halves.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ c. Close the filter shell by screwing the 2 halves together until you can twist no further.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ d. Repeat steps a-c for second filter shell.</td>\n</tr>\n</tbody>\n</table></div>" }

4. Attach filter shells

{ "type": "p", "children": [], "text": "\n4. Attach filter shells\n" }

Insert 1 filter shell into the filter shell port on the side of the dome assembly and insert the second filter shell into the port on the bottom of the inhalation piece. The filter shells are the same and can be used in either port. You can turn the filter shells around to fit into the ports, as needed.

{ "type": "p", "children": [], "text": "Insert 1 filter shell into the filter shell port on the side of the dome assembly and insert the second filter shell into the port on the bottom of the inhalation piece. The filter shells are the same and can be used in either port. You can turn the filter shells around to fit into the ports, as needed." }

Make sure to insert filter shells straight into ports, not at an angle.

{ "type": "p", "children": [], "text": "Make sure to insert filter shells straight into ports, not at an angle." }

5. Insert inhalation piece

{ "type": "p", "children": [], "text": "\n5. Insert inhalation piece\n" }

Insert the inhalation piece with attached filter shell into the upper opening of the dome assembly and turn it toward the front of the device. Gently push down the inhalation piece to make sure it is securely inserted in the dome assembly.

{ "type": "p", "children": [], "text": "Insert the inhalation piece with attached filter shell into the upper opening of the dome assembly and turn it toward the front of the device. Gently push down the inhalation piece to make sure it is securely inserted in the dome assembly." }

6. Insert mouthpiece

{ "type": "p", "children": [], "text": "\n6. Insert mouthpiece\n" }

Carefully insert the mouthpiece into the inhalation piece.

{ "type": "p", "children": [], "text": "Carefully insert the mouthpiece into the inhalation piece." }

7. Check assembled device

{ "type": "p", "children": [], "text": "\n7. Check assembled device\n" }

When the device is fully assembled, it should look like it does below. Slightly turn the inhalation piece so you can see the display screen, which provides important prompts during your treatment.

{ "type": "p", "children": [], "text": "When the device is fully assembled, it should look like it does below. Slightly turn the inhalation piece so you can see the display screen, which provides important prompts during your treatment." }

Important: Do not use device if you see liquid leaking from bottom of the device.

{ "type": "p", "children": [], "text": "\nImportant: Do not use device if you see liquid leaking from bottom of the device." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">E: Power on inhalation device</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">E: Power on inhalation device</span></td>\n</tr>\n</tbody>\n</table></div>" }

1. Power on device

{ "type": "p", "children": [], "text": "\n1. Power on device\n" }

Press and hold the On/Off button until the screen turns on and the device beeps once.

{ "type": "p", "children": [], "text": "Press and hold the On/Off button until the screen turns on and the device beeps once." }

The screen will display the splash screen, then the time since your last treatment, then the current breaths programmed for each dose.

{ "type": "p", "children": [], "text": "The screen will display the splash screen, then the time since your last treatment, then the current breaths programmed for each dose." }

Important: Make sure the number on screen above "Breaths left" matches the prescribed number of breaths for that treatment session. If it does not match, see page 22 for instructions on setting the number of breaths for a treatment session.

{ "type": "p", "children": [], "text": "\nImportant: Make sure the number on screen above \"Breaths left\" matches the prescribed number of breaths for that treatment session. If it does not match, see page 22 for instructions on setting the number of breaths for a treatment session." }

2. Plug in device, if needed

{ "type": "p", "children": [], "text": "\n2. Plug in device, if needed\n" }

If the device's internal battery is too low to deliver a full treatment, the screen will display an instruction to plug in the power to charge the device battery. If the battery is fully depleted, the screen will not turn on.

{ "type": "p", "children": [], "text": "If the device's internal battery is too low to deliver a full treatment, the screen will display an instruction to plug in the power to charge the device battery. If the battery is fully depleted, the screen will not turn on." }

You can charge the battery at any time, before the screen displays "Charge battery."

{ "type": "p", "children": [], "text": "You can charge the battery at any time, before the screen displays \"Charge battery.\"" }

You can conduct a treatment session with the power plugged in. First, plug the AC wall plug's white connector into the port on the back of the inhalation device. Then, plug the AC wall plug into the wall outlet. The power status light above the port will light green when properly plugged in.

{ "type": "p", "children": [], "text": "You can conduct a treatment session with the power plugged in. First, plug the AC wall plug's white connector into the port on the back of the inhalation device. Then, plug the AC wall plug into the wall outlet. The power status light above the port will light green when properly plugged in." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">F: Inhale your medicine</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">F: Inhale your medicine</span></td>\n</tr>\n</tbody>\n</table></div>" }

1. Before starting, confirm treatment

{ "type": "p", "children": [], "text": "\n1. Before starting, confirm treatment\n" }

You will breathe in (inhale) TYVASO during 4 treatment sessions each day (evenly spaced during your waking hours). During each treatment session, you will take a series of breaths through the mouthpiece of the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nYou will breathe in (inhale) TYVASO during 4 treatment sessions each day (evenly spaced during your waking hours). During each treatment session, you will take a series of breaths through the mouthpiece of the TYVASO Inhalation System.\n" }

Before inhaling your medicine, ensure the Run/Program switch is in the 'Run' position, and make sure the number displayed on screen matches your prescribed number of breaths for that treatment session. During the treatment the device counts down each breath after a set time interval. Once you complete all breaths, record the breath number in your Treatment Tracker.

{ "type": "p", "children": [], "text": "Before inhaling your medicine, ensure the Run/Program switch is in the 'Run' position, and make sure the number displayed on screen matches your prescribed number of breaths for that treatment session. During the treatment the device counts down each breath after a set time interval. Once you complete all breaths, record the breath number in your Treatment Tracker." }

Important: If the number of breaths displayed does not match the number of breaths in your prescription, see page 22 "Setting your prescribed dose" and repeat steps 1-4.

{ "type": "p", "children": [], "text": "\nImportant: If the number of breaths displayed does not match the number of breaths in your prescription, see page 22 \"Setting your prescribed dose\" and repeat steps 1-4." }

2. Hold the device upright

{ "type": "p", "children": [], "text": "\n2. Hold the device upright\n" }

Hold the device upright and stand or sit in an upright position as shown below. Avoid covering the bottom of the device so that the audio speaker is not blocked.

{ "type": "p", "children": [], "text": "Hold the device upright and stand or sit in an upright position as shown below. Avoid covering the bottom of the device so that the audio speaker is not blocked." }

Make sure you can see the display screen and lights clearly and that your hands do not cover the display screen or lights while holding device. If needed, you can move the inhalation piece and mouthpiece slightly to either side to see the screen and lights better.

{ "type": "p", "children": [], "text": "Make sure you can see the display screen and lights clearly and that your hands do not cover the display screen or lights while holding device. If needed, you can move the inhalation piece and mouthpiece slightly to either side to see the screen and lights better." }

See next page to start treatment.

{ "type": "p", "children": [], "text": "See next page to start treatment." }

Inhalation tips:

{ "type": "p", "children": [], "text": "\nInhalation tips:\n" }

Technique:

{ "type": "p", "children": [], "text": "\nTechnique:\n" }

When breathing each TYVASO treatment, be sure to keep the device level, directing the flow of medicine into the throat and not toward the roof of the mouth.

{ "type": "p", "children": [], "text": "When breathing each TYVASO treatment, be sure to keep the device level, directing the flow of medicine into the throat and not toward the roof of the mouth." }

Seal your lips around the mouthpiece to ensure that you can inhale the full amount of TYVASO after it is produced by the device.

{ "type": "p", "children": [], "text": "Seal your lips around the mouthpiece to ensure that you can inhale the full amount of TYVASO after it is produced by the device." }

Inhalation:

{ "type": "p", "children": [], "text": "\nInhalation:\n" }

Each breath should last approximately 3 seconds, breathing "normal full breaths." Do not hold your breath. Remove your lips from the mouthpiece, breathe out (exhale) normally and prepare for the next breath.

{ "type": "p", "children": [], "text": "Each breath should last approximately 3 seconds, breathing \"normal full breaths.\" Do not hold your breath. Remove your lips from the mouthpiece, breathe out (exhale) normally and prepare for the next breath." }

3. Press blue button to start treatment

{ "type": "p", "children": [], "text": "\n3. Press blue button to start treatment\n" }

If you need to pause treatment, you can press and immediately release (do not hold down) the blue button. Press the button again and immediately release to resume treatment. (Note: If you do not resume treatment after pausing, power off device.)

{ "type": "p", "children": [], "text": "If you need to pause treatment, you can press and immediately release (do not hold down) the blue button. Press the button again and immediately release to resume treatment. (Note: If you do not resume treatment after pausing, power off device.)" }

4. Wait

{ "type": "p", "children": [], "text": "\n4. Wait\n" }

Look at the display screen for cues. Wait until you hear 2 short beeps. When you hear 1 long beep, exhale to prepare to inhale.

{ "type": "p", "children": [], "text": "Look at the display screen for cues. Wait until you hear 2 short beeps. When you hear 1 long beep, exhale to prepare to inhale." }

5. Inhale

{ "type": "p", "children": [], "text": "\n5. Inhale\n" }

When you hear 1 short beep and the indicator lights flash green, place your lips securely around the mouthpiece and inhale for 3 seconds. When lights stop flashing, remove lips from mouthpiece and exhale normally.

{ "type": "p", "children": [], "text": "When you hear 1 short beep and the indicator lights flash green, place your lips securely around the mouthpiece and inhale for 3 seconds. When lights stop flashing, remove lips from mouthpiece and exhale normally." }

6. Repeat for each breath left

{ "type": "p", "children": [], "text": "\n6. Repeat for each breath left\n" }

The screen will decrease the number of breaths left by 1. Repeat steps 4 and 5 for the number of prescribed breaths.

{ "type": "p", "children": [], "text": "The screen will decrease the number of breaths left by 1. Repeat steps 4 and 5 for the number of prescribed breaths." }

7. Finish session

{ "type": "p", "children": [], "text": "\n7. Finish session\n" }

After displaying the last breath sequence, the green Done screen appears, you will hear a beep, and your treatment is done.

{ "type": "p", "children": [], "text": "After displaying the last breath sequence, the green Done screen appears, you will hear a beep, and your treatment is done." }

If the device is left in the "✓ Done" mode for more than 60 seconds, it will turn off automatically.

{ "type": "p", "children": [], "text": "If the device is left in the \"✓ Done\" mode for more than 60 seconds, it will turn off automatically." }

8. Record breaths, turn off device

{ "type": "p", "children": [], "text": "\n8. Record breaths, turn off device\n" }

Record the number of breaths you inhaled on the Treatment Tracker.

{ "type": "p", "children": [], "text": "Record the number of breaths you inhaled on the Treatment Tracker." }

Press and hold blue button until screen turns off.

{ "type": "p", "children": [], "text": "Press and hold blue button until screen turns off." }

 CAUTION: If medicine does not appear to be flowing properly, the system might be set up incorrectly. See "Troubleshooting", starting on page 64 for details.

{ "type": "p", "children": [], "text": "\n CAUTION: If medicine does not appear to be flowing properly, the system might be set up incorrectly. See \"Troubleshooting\", starting on page 64 for details." }

Cleaning and Storing your TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nCleaning and Storing your TYVASO Inhalation System\n" }

Section overview

{ "type": "p", "children": [], "text": "\nSection overview\n" }

This section provides instructions for storing your TYVASO Inhalation System after each treatment and daily and weekly cleaning.

{ "type": "p", "children": [], "text": "This section provides instructions for storing your TYVASO Inhalation System after each treatment and daily and weekly cleaning." }

There is also information about your monthly refill kits, replacing your device, and recharging the device's battery.

{ "type": "p", "children": [], "text": "There is also information about your monthly refill kits, replacing your device, and recharging the device's battery." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">What you will need:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  ▶ A clean place to work with the device</td> </tr> <tr class="Botrule"> <td align="left">  ▶ TYVASO Inhalation device</td> </tr> <tr class="Botrule"> <td align="left">  ▶ TYVASO Inhalation supplies</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">What you will need:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ A clean place to work with the device</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ TYVASO Inhalation device</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ TYVASO Inhalation supplies</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="80%"/> <col align="right" valign="bottom" width="20%"/> <thead> <tr> <th align="left" colspan="2">What is covered in this section:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  A: Storing between sessions during the day</td><td align="right">48</td> </tr> <tr class="Botrule"> <td align="left">  B: End of day cleaning</td><td align="right">52</td> </tr> <tr class="Botrule"> <td align="left">  C: Recharging the battery</td><td align="right">57</td> </tr> <tr class="Botrule"> <td align="left">  D: Weekly cleaning</td><td align="right">59</td> </tr> <tr class="Botrule"> <td align="left">  E: Monthly Refill Kit</td><td align="right">60</td> </tr> <tr class="Botrule"> <td align="left">  F: Replacing your devices</td><td align="right">61</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"80%\"/>\n<col align=\"right\" valign=\"bottom\" width=\"20%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"2\">What is covered in this section:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  A: Storing between sessions during the day</td><td align=\"right\">48</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  B: End of day cleaning</td><td align=\"right\">52</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  C: Recharging the battery</td><td align=\"right\">57</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  D: Weekly cleaning</td><td align=\"right\">59</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  E: Monthly Refill Kit</td><td align=\"right\">60</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  F: Replacing your devices</td><td align=\"right\">61</td>\n</tr>\n</tbody>\n</table></div>" }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

For further support, you can:

{ "type": "p", "children": [], "text": "For further support, you can:" }

{ "type": "ul", "children": [ "Fill out and refer to your emergency contact information on the back of this Instructions for Use manual.", "Call 1-877-UNITHER (1-877-864-8437) for questions and information, or to report an adverse reaction." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">A: Storing between sessions during the day</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">A: Storing between sessions during the day</span></td>\n</tr>\n</tbody>\n</table></div>" }

If you have more treatment sessions left in the day, perform the steps in this section.

{ "type": "p", "children": [], "text": "\nIf you have more treatment sessions left in the day, perform the steps in this section.\n" }

If you have completed your last treatment session of the day, skip to "End of day cleaning" on page 52.

{ "type": "p", "children": [], "text": "\nIf you have completed your last treatment session of the day, skip to \"End of day cleaning\" on page 52.\n" }

Be sure to pack all parts, including the AC wall plug, in the carrying case whenever transporting your device.

{ "type": "p", "children": [], "text": "Be sure to pack all parts, including the AC wall plug, in the carrying case whenever transporting your device." }

1. Disconnect AC wall plug (if it is currently connected)

{ "type": "p", "children": [], "text": "\n1. Disconnect AC wall plug\n(if it is currently connected)" }

2. Remove mouthpiece

{ "type": "p", "children": [], "text": "\n2. Remove mouthpiece\n" }

3. Remove inhalation piece

{ "type": "p", "children": [], "text": "\n3. Remove inhalation piece\n" }

Important: When removing accessories between treatment sessions, hold the device by its base to avoid spilling the medicine.

{ "type": "p", "children": [], "text": "\nImportant: When removing accessories between treatment sessions, hold the device by its base to avoid spilling the medicine." }

4. Remove both filter shells

{ "type": "p", "children": [], "text": "\n4. Remove both filter shells\n" }

Note: Do not remove the filter membranes from filter shells until after the last treatment session of the day.

{ "type": "p", "children": [], "text": "Note: Do not remove the filter membranes from filter shells until after the last treatment session of the day." }

5. Leave dome assembly

{ "type": "p", "children": [], "text": "\n5. Leave dome assembly\n" }

Leave dome assembly and medicine cup (with the medicine still in it) attached to the device.

{ "type": "p", "children": [], "text": "Leave dome assembly and medicine cup (with the medicine still in it) attached to the device." }

6. Place plugs in dome assembly

{ "type": "p", "children": [], "text": "\n6. Place plugs in dome assembly\n" }

Insert a plug into each of the 2 open holes on the dome assembly to prevent the medicine from spilling out.

{ "type": "p", "children": [], "text": "Insert a plug into each of the 2 open holes on the dome assembly to prevent the medicine from spilling out." }

Important: If the plugs are not in place, the medicine may spill. If you spill any medicine, discard remaining medicine and start your next treatment with a new ampule.

{ "type": "p", "children": [], "text": "\nImportant: If the plugs are not in place, the medicine may spill. If you spill any medicine, discard remaining medicine and start your next treatment with a new ampule." }

7. Store in carrying case

{ "type": "p", "children": [], "text": "\n7. Store in carrying case\n" }

You can store the inhalation device with the plugged dome assembly and disassembled accessories in the carrying case between treatment sessions.

{ "type": "p", "children": [], "text": "You can store the inhalation device with the plugged dome assembly and disassembled accessories in the carrying case between treatment sessions." }

Keep the carrying case upright while inserting the device and components so that water and medicine does not spill out of the device.

{ "type": "p", "children": [], "text": "Keep the carrying case upright while inserting the device and components so that water and medicine does not spill out of the device." }

Important: Store the inhalation device in an upright position until the next treatment session. See "Specifications" on page 76 for additional storage and transport information.

{ "type": "p", "children": [], "text": "\nImportant: Store the inhalation device in an upright position until the next treatment session. See \"Specifications\" on page 76 for additional storage and transport information." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">B: End of day cleaning</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">B: End of day cleaning</span></td>\n</tr>\n</tbody>\n</table></div>" }

If you have completed your last treatment session of the day, perform the steps in this section.

{ "type": "p", "children": [], "text": "\nIf you have completed your last treatment session of the day, perform the steps in this section.\n" }

If you have more treatment sessions left in the day, refer back to "Storing between sessions during the day" on page 48.

{ "type": "p", "children": [], "text": "\nIf you have more treatment sessions left in the day, refer back to \"Storing between sessions during the day\" on page 48.\n" }

1. Disconnect AC wall plug (if it is currently connected)

{ "type": "p", "children": [], "text": "\n1. Disconnect AC wall plug\n(if it is currently connected)" }

2. Remove mouthpiece

{ "type": "p", "children": [], "text": "\n2. Remove mouthpiece\n" }

3. Remove inhalation piece with attached filter shell

{ "type": "p", "children": [], "text": "\n3. Remove inhalation piece with attached filter shell\n" }

4. Remove both filter shells

{ "type": "p", "children": [], "text": "\n4. Remove both filter shells\n" }

5. Discard filter membranes

{ "type": "p", "children": [], "text": "\n5. Discard filter membranes\n" }

Open filter shells by twisting in opposite directions. Remove and discard used filter membranes in the trash.

{ "type": "p", "children": [], "text": "Open filter shells by twisting in opposite directions. Remove and discard used filter membranes in the trash." }

6. Remove dome assembly

{ "type": "p", "children": [], "text": "\n6. Remove dome assembly\n" }

Remove the dome assembly by turning it counter-clockwise (to the left). The medicine cup should stay attached to the dome assembly.

{ "type": "p", "children": [], "text": "Remove the dome assembly by turning it counter-clockwise (to the left). The medicine cup should stay attached to the dome assembly." }

7. Remove medicine cup

{ "type": "p", "children": [], "text": "\n7. Remove medicine cup\n" }

Remove the medicine cup by gently squeezing on the sides where it is attached to the dome assembly.

{ "type": "p", "children": [], "text": "Remove the medicine cup by gently squeezing on the sides where it is attached to the dome assembly." }

Be careful not to spill any leftover medicine.

{ "type": "p", "children": [], "text": "Be careful not to spill any leftover medicine." }

 CAUTION: If any medicine from the medicine cup spills on your hands, wash your hands immediately. Medicine contact with the skin can cause irritation.

{ "type": "p", "children": [], "text": "\n CAUTION: If any medicine from the medicine cup spills on your hands, wash your hands immediately. Medicine contact with the skin can cause irritation." }

8. Empty medicine cup

{ "type": "p", "children": [], "text": "\n8. Empty medicine cup\n" }

Empty any leftover medicine in the medicine cup into a waste basket, and discard the medicine cup.

{ "type": "p", "children": [], "text": "Empty any leftover medicine in the medicine cup into a waste basket, and discard the medicine cup." }

Important: Discard remaining TYVASO® (treprostinil) Inhalation Solution in an appropriate waste receptacle. Discard plastic medicine cup in the trash.

{ "type": "p", "children": [], "text": "\nImportant: Discard remaining TYVASO® (treprostinil) Inhalation Solution in an appropriate waste receptacle. Discard plastic medicine cup in the trash." }

Do not reuse or recycle medicine cup.

{ "type": "p", "children": [], "text": "Do not reuse or recycle medicine cup." }

9. Empty and clean device

{ "type": "p", "children": [], "text": "\n9. Empty and clean device\n" }

Empty distilled water from water chamber and let inhalation device air dry upside down. You can wipe the water chamber with a soft cloth or paper towel to remove any remaining water.

{ "type": "p", "children": [], "text": "Empty distilled water from water chamber and let inhalation device air dry upside down. You can wipe the water chamber with a soft cloth or paper towel to remove any remaining water." }

Important: Do not place the inhalation device in water or in a dishwasher.

{ "type": "p", "children": [], "text": "\nImportant: Do not place the inhalation device in water or in a dishwasher." }

10. Clean accessories

{ "type": "p", "children": [], "text": "\n10. Clean accessories\n" }

Clean accessories (pictured below) by hand in mild, soapy, warm water, then rinse them thoroughly with water. Allow accessories to air dry.

{ "type": "p", "children": [], "text": "Clean accessories (pictured below) by hand in mild, soapy, warm water, then rinse them thoroughly with water. Allow accessories to air dry." }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="center" valign="top" width="50%"/> <col align="center" valign="top" width="50%"/> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-203.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-204.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Dome assembly</td><td align="center">Inhalation piece</td> </tr> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-205.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-206.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Mouthpiece</td><td align="center">Filter shells</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"center\" valign=\"top\" width=\"50%\"/>\n<col align=\"center\" valign=\"top\" width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-203.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-204.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Dome assembly</td><td align=\"center\">Inhalation piece</td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-205.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-206.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Mouthpiece</td><td align=\"center\">Filter shells</td>\n</tr>\n</tbody>\n</table></div>" }

Important: Do not place the inhalation device or its accessories in a microwave, conventional oven, or dishwasher.

{ "type": "p", "children": [], "text": "\nImportant: Do not place the inhalation device or its accessories in a microwave, conventional oven, or dishwasher." }

11. Store components

{ "type": "p", "children": [], "text": "\n11. Store components\n" }

Once all the items are dry, you can store the filter shells, inhalation piece, mouthpiece, dome assembly, AC wall plug, and inhalation device in the carrying case until the next day's treatment sessions.

{ "type": "p", "children": [], "text": "Once all the items are dry, you can store the filter shells, inhalation piece, mouthpiece, dome assembly, AC wall plug, and inhalation device in the carrying case until the next day's treatment sessions." }

You can also recharge the device for the next day of use (see page 57).

{ "type": "p", "children": [], "text": "You can also recharge the device for the next day of use (see page 57)." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">C: Recharging the battery</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">C: Recharging the battery</span></td>\n</tr>\n</tbody>\n</table></div>" }

1. Checking the battery's status

{ "type": "p", "children": [], "text": "\n1. Checking the battery's status\n" }

You can recharge your battery at any time. Press and hold the blue button to power on the device to check battery status. Make sure the Run / Program switch is set to Run.

{ "type": "p", "children": [], "text": "You can recharge your battery at any time. Press and hold the blue button to power on the device to check battery status. Make sure the Run / Program switch is set to Run." }

{ "type": "ul", "children": [ "The battery icon at the bottom of the screen indicates battery status:" ], "text": "" }

{ "type": "ul", "children": [ "\"Charge battery\" appears on screen if there is not enough charge to conduct a treatment session." ], "text": "" }

Important: Always charge the device before you first use it. You should also charge the device when not in use and in between uses.

{ "type": "p", "children": [], "text": "\nImportant: Always charge the device before you first use it. You should also charge the device when not in use and in between uses." }

2. Charging the battery

{ "type": "p", "children": [], "text": "\n2. Charging the battery\n" }

Plug the AC wall plug's white connector into the port on the back of the inhalation device. Then, plug the AC wall plug into the wall outlet. The power status light above the port will light green when properly plugged in.

{ "type": "p", "children": [], "text": "Plug the AC wall plug's white connector into the port on the back of the inhalation device. Then, plug the AC wall plug into the wall outlet. The power status light above the port will light green when properly plugged in." }

The device battery might take up to 8 hours to fully charge.

{ "type": "p", "children": [], "text": "The device battery might take up to 8 hours to fully charge." }

If the device is powered on, the battery charging icon appears next to the battery icon at the bottom of the screen.

{ "type": "p", "children": [], "text": "If the device is powered on, the battery charging icon appears next to the battery icon at the bottom of the screen." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="center" valign="top" width="100%"/> <tbody class="Headless"> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-209.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Battery charging icon</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"center\" valign=\"top\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-209.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Battery charging icon</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">D: Weekly cleaning</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">D: Weekly cleaning</span></td>\n</tr>\n</tbody>\n</table></div>" }

Clean the device once a week to help avoid corrosion and leaks and to keep your device working properly.

{ "type": "p", "children": [], "text": "Clean the device once a week to help avoid corrosion and leaks and to keep your device working properly." }

Once a week, use a clean, dry cloth to wipe the interior of the water chamber. Make sure to wipe the 2 silver sensors and the white disc in the bottom of the water chamber.

{ "type": "p", "children": [], "text": "Once a week, use a clean, dry cloth to wipe the interior of the water chamber. Make sure to wipe the 2 silver sensors and the white disc in the bottom of the water chamber." }

You may wipe the exterior of the device with a damp cloth if the lights or buttons become difficult to see.

{ "type": "p", "children": [], "text": "You may wipe the exterior of the device with a damp cloth if the lights or buttons become difficult to see." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">E: Monthly Refill Kit</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">E: Monthly Refill Kit</span></td>\n</tr>\n</tbody>\n</table></div>" }

Once a month, you will receive a refill kit that will come with a new set of accessories from your specialty pharmacy provider.

{ "type": "p", "children": [], "text": "Once a month, you will receive a refill kit that will come with a new set of accessories from your specialty pharmacy provider." }

{ "type": "ul", "children": [ "Inspect the shipment to be sure all parts are included.", "Once the new kit has arrived, discard the used dome assembly, inhalation piece, mouthpiece, filter shells, and plugs.", "Do not recycle the used accessories." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="75%"> <col align="center" valign="top" width="34%"/> <col align="center" valign="top" width="33%"/> <col align="center" valign="top" width="33%"/> <tbody class="Headless"> <tr> <td align="right"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-213.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" colspan="2"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-214.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Dome assembly</td><td align="center" colspan="2">2 filter shells</td> </tr> <tr> <td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-215.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-216.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-217.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Mouthpiece</td><td align="center">Inhalation piece</td><td align="center">2 plugs</td> </tr> <tr> <td align="right"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-218.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="center" colspan="2"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-219.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> <tr> <td align="center">Filter membranes</td><td align="center" colspan="2">Medicine cups</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"75%\">\n<col align=\"center\" valign=\"top\" width=\"34%\"/>\n<col align=\"center\" valign=\"top\" width=\"33%\"/>\n<col align=\"center\" valign=\"top\" width=\"33%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"right\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-213.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" colspan=\"2\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-214.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Dome assembly</td><td align=\"center\" colspan=\"2\">2 filter shells</td>\n</tr>\n<tr>\n<td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-215.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-216.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-217.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Mouthpiece</td><td align=\"center\">Inhalation piece</td><td align=\"center\">2 plugs</td>\n</tr>\n<tr>\n<td align=\"right\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-218.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"center\" colspan=\"2\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-219.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n<tr>\n<td align=\"center\">Filter membranes</td><td align=\"center\" colspan=\"2\">Medicine cups</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">F: Replacing your devices</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">F: Replacing your devices</span></td>\n</tr>\n</tbody>\n</table></div>" }

The inhalation devices should be replaced every 2 years from your first day of use. Replacement inhalation devices will be supplied by your specialty pharmacy provider.

{ "type": "p", "children": [], "text": "The inhalation devices should be replaced every 2 years from your first day of use. Replacement inhalation devices will be supplied by your specialty pharmacy provider." }

When you receive a new inhalation device your specialty pharmacy provider will provide instructions for returning the old device.

{ "type": "p", "children": [], "text": "When you receive a new inhalation device your specialty pharmacy provider will provide instructions for returning the old device." }

Help / More information about your TYVASO Inhalation System

{ "type": "p", "children": [], "text": "\nHelp / More information about your TYVASO Inhalation System\n" }

Section overview

{ "type": "p", "children": [], "text": "\nSection overview\n" }

This section provides additional information about your device. Use this section to troubleshoot difficulties you have with the device, or to learn more about the device's specifications and warranty.

{ "type": "p", "children": [], "text": "This section provides additional information about your device. Use this section to troubleshoot difficulties you have with the device, or to learn more about the device's specifications and warranty." }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">What you will need:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  ▶ Access to a phone (to contact support if troubleshooting steps do not resolve the problem)</td> </tr> <tr class="Botrule"> <td align="left">  ▶ A clean place to work with the device</td> </tr> <tr class="Botrule"> <td align="left">  ▶ TYVASO Inhalation Device or supplies, as needed</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">What you will need:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ Access to a phone (to contact support if troubleshooting steps do not resolve the problem)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ A clean place to work with the device</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  ▶ TYVASO Inhalation Device or supplies, as needed</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="80%"/> <col align="right" valign="bottom" width="20%"/> <thead> <tr> <th align="left" colspan="2">What is covered in this section:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">  A: Troubleshooting</td><td align="right">64</td> </tr> <tr class="Botrule"> <td align="left">  B: Specifications</td><td align="right">76</td> </tr> <tr class="Botrule"> <td align="left">  C: Electromagnetic compatibility (EMC)</td><td align="right">79</td> </tr> <tr class="Botrule"> <td align="left">  D: Glossary</td><td align="right">87</td> </tr> <tr class="Botrule"> <td align="left">  E: Warranty information</td><td align="right">90</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"80%\"/>\n<col align=\"right\" valign=\"bottom\" width=\"20%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"2\">What is covered in this section:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">  A: Troubleshooting</td><td align=\"right\">64</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  B: Specifications</td><td align=\"right\">76</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  C: Electromagnetic compatibility (EMC)</td><td align=\"right\">79</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  D: Glossary</td><td align=\"right\">87</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">  E: Warranty information</td><td align=\"right\">90</td>\n</tr>\n</tbody>\n</table></div>" }

Important:

{ "type": "p", "children": [], "text": "\nImportant:\n" }

For further support, you can:

{ "type": "p", "children": [], "text": "For further support, you can:" }

{ "type": "ul", "children": [ "Fill out and refer to your emergency contact information on the back of this Instructions for Use manual.", "Call 1-877-UNITHER (1-877-864-8437) for questions and information, or to report an adverse reaction." ], "text": "" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">A: Troubleshooting</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">A: Troubleshooting</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="35%"/> <col align="left" valign="top" width="35%"/> <thead> <tr class="First Last"> <th align="left">Problem</th><th align="left">Possible causes</th><th align="left">Corrective actions</th> </tr> </thead> <tbody> <tr class="First"> <td align="left" rowspan="4"><span class="Bold">Charge Battery screen appears<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-132.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></span></td><td align="left" class="Botrule">Low battery</td><td align="left" class="Botrule">Charge the device battery by attaching the AC wall plug to an outlet. You can conduct a treatment session with the device plugged in.</td> </tr> <tr> <td align="left">AC wall plug not properly connected<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-220.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Ensure that the plug adapter piece (the detachable piece with the metal prongs) is securely attached to the AC wall plug. Then, make sure the AC wall plug is properly connected to an outlet and device. The status lights on the back of the AC wall plug and device should light green. You can conduct a treatment session with the device plugged in.</td> </tr> <tr> <td align="left" class="Botrule">AC wall plug is defective<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-221.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Use the replacement AC wall plug. Confirm that status light on AC wall plug is green when plugged in. You can conduct a treatment session with the device plugged in.</td> </tr> <tr> <td align="left" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="4"><span class="Bold">Screen does not turn on<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-222.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></span></td><td align="left" class="Botrule">Device battery is completely empty</td><td align="left" class="Botrule">Charge the device battery by attaching the AC wall plug to an outlet. You can conduct a treatment session with the device plugged in.</td> </tr> <tr> <td align="left">AC wall plug not properly connected<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-220a.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Ensure that the plug adapter piece (the detachable piece with the metal prongs) is securely attached to the AC wall plug. Then, make sure the AC wall plug is properly connected to an outlet and device. The status lights on the back of the AC wall plug and device should light green. You can conduct a treatment session with the device plugged in.</td> </tr> <tr> <td align="left" class="Botrule">AC wall plug is defective<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-223.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Use the replacement AC wall plug. Confirm that status light on AC wall plug is green when plugged in. You can conduct a treatment session with the device plugged in.</td> </tr> <tr> <td align="left" class="Botrule" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="2"><span class="Bold">Call Support screen appears<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-129.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></span></td><td align="left" class="Botrule">Temporary device failure.</td><td align="left" class="Botrule">If device is plugged in, unplug device and wait for the device to power off. Power on device from internal battery and check that Call Support screen does not reappear. Continue taking breaths to complete the treatment session.</td> </tr> <tr> <td align="left" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="3"><span class="Bold">Loss of power during treatment</span></td><td align="left" class="Botrule">Device is disconnected from power source and battery is empty</td><td align="left" class="Botrule">Reconnect device to power source and confirm the power status light on back of device is green (battery is charging). Press and <span class="Bold">hold</span> the blue On/Off button to turn on the device. The display will show how many breaths are left in that treatment session. Press <span class="Bold">and immediately</span> release (do not hold down) the blue button again to continue your treatment session.</td> </tr> <tr> <td align="left" class="Botrule">Power source is temporarily disrupted (for example, electricity interruption due to a storm)</td><td align="left" class="Botrule">Reconnect device to power source and confirm the power status light on back of device is green (battery is charging). Press and <span class="Bold">hold</span> the blue On/Off button to turn on the device. The display will show how many breaths are left in that treatment session. Press <span class="Bold">and immediately</span> release (do not hold down) the blue button again to continue your treatment session.</td> </tr> <tr> <td align="left" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="4"><span class="Bold">Add Water screen appears<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-131.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></span></td><td align="left">Water chamber is empty or distilled water level is too low.<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-224.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Then empty water chamber.<br/>Refill water chamber with distilled water using water level cup (see page 32). Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left">The distilled water is too pure.</td><td align="left">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Then empty water chamber.<br/>Add 1 teaspoon of tap water to the water level cup. Fill rest of cup with distilled water up to level between the 2 arrow markings on cup (see page 32). Pour cup's contents into water chamber. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left" class="Botrule">Water level sensors have a thin layer of build-up<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-225.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Then empty water chamber.<br/>Clean sensors and interior surfaces of water chamber with a clean cloth. Refill water chamber with distilled water using water level cup (see page 32). Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="5"><span class="Bold">No "click" (or crunch) was heard when attaching the dome assembly </span></td><td align="left" class="Botrule">No medicine cup in the water chamber of the device</td><td align="left" class="Botrule">Unplug device, if plugged in, and power off device. Place an empty medicine cup into the water chamber of the device and fill it with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left">Multiple medicine cups attached to the dome assembly<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-226.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Unplug device, if plugged in, and power off device. Remove and dispose of all medicine cups in the device. Place a single, new medicine cup into device water chamber and fill with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left">Dome assembly is not securely in place</td><td align="left">Unplug device, if plugged in, and power off device.<br/>Align the raised circle on the side of the dome assembly with the raised circle on the side of the device.</td> </tr> <tr> <td align="left" class="Botrule"><img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-227.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Push down and screw the dome assembly onto the device clockwise (right) until the filter shell port is tight and pointed to the back of the device and the raised circles line up again. You will hear clicks (or crunch sound) as the dome assembly presses down on the medicine cup. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="5"><span class="Bold">No medicine comes out of the device during a treatment session </span></td><td align="left" class="Botrule">No TYVASO<span class="Sup">®</span> (treprostinil) Inhalation Solution in the medicine cup<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-228.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Unplug device, if plugged in, and power off device. Fill medicine cup with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left" class="Botrule">Damaged medicine cup<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-229.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Unplug device, if plugged in, and power off device. Remove and dispose of the medicine cup in the device. Empty the water chamber then refill it with 45 mL of distilled water (see page 32). Place a single, new medicine cup into water chamber and fill with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left">Distilled water level in the water chamber is too high<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-230.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Empty the water chamber then refill it with 45 mL of distilled water (see page 32). Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left" class="Botrule">Multiple medicine cups attached to the dome assembly<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-231.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Unplug device, if plugged in, and power off device. Remove and dispose of all medicine cups in the device. Place a single, new medicine cup into water chamber and fill with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td> </tr> <tr> <td align="left" class="Botrule" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> <tr> <td align="left" rowspan="2"><span class="Bold">Difficult to breathe in medicine through the mouthpiece</span></td><td align="left" class="Botrule">Filter membrane is clogged<br/> <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-232.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td><td align="left" class="Botrule">Unplug device, if plugged in, and power off device. Replace both filter membranes (see page 37). Reassemble device. Power the device on and continue treatment.</td> </tr> <tr class="Last"> <td align="left" colspan="2">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"35%\"/>\n<col align=\"left\" valign=\"top\" width=\"35%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\">Problem</th><th align=\"left\">Possible causes</th><th align=\"left\">Corrective actions</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\" rowspan=\"4\"><span class=\"Bold\">Charge Battery screen appears<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-132.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></span></td><td align=\"left\" class=\"Botrule\">Low battery</td><td align=\"left\" class=\"Botrule\">Charge the device battery by attaching the AC wall plug to an outlet. You can conduct a treatment session with the device plugged in.</td>\n</tr>\n<tr>\n<td align=\"left\">AC wall plug not properly connected<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-220.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Ensure that the plug adapter piece (the detachable piece with the metal prongs) is securely attached to the AC wall plug. Then, make sure the AC wall plug is properly connected to an outlet and device. The status lights on the back of the AC wall plug and device should light green. You can conduct a treatment session with the device plugged in.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">AC wall plug is defective<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-221.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Use the replacement AC wall plug. Confirm that status light on AC wall plug is green when plugged in. You can conduct a treatment session with the device plugged in.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"4\"><span class=\"Bold\">Screen does not turn on<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-222.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></span></td><td align=\"left\" class=\"Botrule\">Device battery is completely empty</td><td align=\"left\" class=\"Botrule\">Charge the device battery by attaching the AC wall plug to an outlet. You can conduct a treatment session with the device plugged in.</td>\n</tr>\n<tr>\n<td align=\"left\">AC wall plug not properly connected<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-220a.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Ensure that the plug adapter piece (the detachable piece with the metal prongs) is securely attached to the AC wall plug. Then, make sure the AC wall plug is properly connected to an outlet and device. The status lights on the back of the AC wall plug and device should light green. You can conduct a treatment session with the device plugged in.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">AC wall plug is defective<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-223.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Use the replacement AC wall plug. Confirm that status light on AC wall plug is green when plugged in. You can conduct a treatment session with the device plugged in.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"2\"><span class=\"Bold\">Call Support screen appears<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-129.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></span></td><td align=\"left\" class=\"Botrule\">Temporary device failure.</td><td align=\"left\" class=\"Botrule\">If device is plugged in, unplug device and wait for the device to power off. Power on device from internal battery and check that Call Support screen does not reappear. Continue taking breaths to complete the treatment session.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"3\"><span class=\"Bold\">Loss of power during treatment</span></td><td align=\"left\" class=\"Botrule\">Device is disconnected from power source and battery is empty</td><td align=\"left\" class=\"Botrule\">Reconnect device to power source and confirm the power status light on back of device is green (battery is charging). Press and <span class=\"Bold\">hold</span> the blue On/Off button to turn on the device. The display will show how many breaths are left in that treatment session. Press <span class=\"Bold\">and immediately</span> release (do not hold down) the blue button again to continue your treatment session.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">Power source is temporarily disrupted (for example, electricity interruption due to a storm)</td><td align=\"left\" class=\"Botrule\">Reconnect device to power source and confirm the power status light on back of device is green (battery is charging). Press and <span class=\"Bold\">hold</span> the blue On/Off button to turn on the device. The display will show how many breaths are left in that treatment session. Press <span class=\"Bold\">and immediately</span> release (do not hold down) the blue button again to continue your treatment session.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"4\"><span class=\"Bold\">Add Water screen appears<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-131.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></span></td><td align=\"left\">Water chamber is empty or distilled water level is too low.<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-224.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Then empty water chamber.<br/>Refill water chamber with distilled water using water level cup (see page 32). Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\">The distilled water is too pure.</td><td align=\"left\">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Then empty water chamber.<br/>Add 1 teaspoon of tap water to the water level cup. Fill rest of cup with distilled water up to level between the 2 arrow markings on cup (see page 32). Pour cup's contents into water chamber. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">Water level sensors have a thin layer of build-up<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-225.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Then empty water chamber.<br/>Clean sensors and interior surfaces of water chamber with a clean cloth. Refill water chamber with distilled water using water level cup (see page 32). Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"5\"><span class=\"Bold\">No \"click\" (or crunch) was heard when attaching the dome assembly \t\t\t\t\t</span></td><td align=\"left\" class=\"Botrule\">No medicine cup in the water chamber of the device</td><td align=\"left\" class=\"Botrule\">Unplug device, if plugged in, and power off device. Place an empty medicine cup into the water chamber of the device and fill it with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\">Multiple medicine cups attached to the dome assembly<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-226.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Unplug device, if plugged in, and power off device. Remove and dispose of all medicine cups in the device. Place a single, new medicine cup into device water chamber and fill with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\">Dome assembly is not securely in place</td><td align=\"left\">Unplug device, if plugged in, and power off device.<br/>Align the raised circle on the side of the dome assembly with the raised circle on the side of the device.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\"><img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-227.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Push down and screw the dome assembly onto the device clockwise (right) until the filter shell port is tight and pointed to the back of the device and the raised circles line up again. You will hear clicks (or crunch sound) as the dome assembly presses down on the medicine cup. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"5\"><span class=\"Bold\">No medicine comes out of the device during a treatment session \t\t\t\t\t</span></td><td align=\"left\" class=\"Botrule\">No TYVASO<span class=\"Sup\">®</span> (treprostinil) Inhalation Solution in the medicine cup<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-228.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Unplug device, if plugged in, and power off device. Fill medicine cup with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">Damaged medicine cup<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-229.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Unplug device, if plugged in, and power off device. Remove and dispose of the medicine cup in the device. Empty the water chamber then refill it with 45 mL of distilled water (see page 32). Place a single, new medicine cup into water chamber and fill with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\">Distilled water level in the water chamber is too high<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-230.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\">Unplug device, if plugged in, and power off device. Remove dome assembly (making sure not to spill medicine) and place it aside, keeping it upright. Empty the water chamber then refill it with 45 mL of distilled water (see page 32). Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\">Multiple medicine cups attached to the dome assembly<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-231.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Unplug device, if plugged in, and power off device. Remove and dispose of all medicine cups in the device. Place a single, new medicine cup into water chamber and fill with 1 ampule of TYVASO. Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n<tr>\n<td align=\"left\" rowspan=\"2\"><span class=\"Bold\">Difficult to breathe in medicine through the mouthpiece</span></td><td align=\"left\" class=\"Botrule\">Filter membrane is clogged<br/>\n<img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-232.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td><td align=\"left\" class=\"Botrule\">Unplug device, if plugged in, and power off device. Replace both filter membranes (see page 37). Reassemble device. Power the device on and continue treatment.</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" colspan=\"2\">If device still does not function after taking corrective actions listed above, contact your specialty pharmacy provider for assistance.</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">B: Specifications</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">B: Specifications</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="90%"> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="left" colspan="2">Inhalation Device</th> </tr> </thead> <tbody> <tr class="First"> <td align="left">Model</td><td align="left"><span class="Bold">TD-300/A</span></td> </tr> <tr> <td align="left">Size</td><td align="left"><span class="Bold">3.5" × 3.2" × 4.7" (90 × 82 × 120 mm)</span></td> </tr> <tr> <td align="left">Weight, inhalation device</td><td align="left"><span class="Bold">365 g (12.8 oz)</span></td> </tr> <tr> <td align="left">Types of power supply</td><td align="left"><span class="Bold">AC wall plug, 120 V, 60 Hz</span></td> </tr> <tr> <td align="left">Power input</td><td align="left"><span class="Bold">14 V DC, 1.1 A maximum</span></td> </tr> <tr> <td align="left">Operating power consumption</td><td align="left"><span class="Bold">18 Watt maximum</span></td> </tr> <tr> <td align="left">Ultrasonic frequency</td><td align="left"><span class="Bold">2.4 MHz (nominal)</span></td> </tr> <tr> <td align="left">Nebulization rate</td><td align="left"><span class="Bold">0.50 - 0.55 mg/min (0.9% Saline)</span></td> </tr> <tr> <td align="left">Medicine cup capacity</td><td align="left"><span class="Bold">6 mL, nominal</span></td> </tr> <tr> <td align="left">Water chamber capacity</td><td align="left"><span class="Bold">45 mL, nominal</span></td> </tr> <tr> <td align="left">Electric protection class</td><td align="left"><span class="Bold">II, Type BF</span></td> </tr> <tr> <td align="left">Storage temperature/humidity</td><td align="left"><span class="Bold">15 to 30ºC/20-80% relative humidity</span></td> </tr> <tr> <td align="left">Operating temperature/humidity</td><td align="left"><span class="Bold">15 to 25ºC/40-75% relative humidity</span></td> </tr> <tr class="Last"> <td align="left">A-weighted sound pressure level</td><td align="left"><span class="Bold">75 dBA (1 m), maximum</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" colspan=\"2\">Inhalation Device</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\">Model</td><td align=\"left\"><span class=\"Bold\">TD-300/A</span></td>\n</tr>\n<tr>\n<td align=\"left\">Size</td><td align=\"left\"><span class=\"Bold\">3.5\" × 3.2\" × 4.7\" (90 × 82 × 120 mm)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Weight, inhalation device</td><td align=\"left\"><span class=\"Bold\">365 g (12.8 oz)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Types of power supply</td><td align=\"left\"><span class=\"Bold\">AC wall plug, 120 V, 60 Hz</span></td>\n</tr>\n<tr>\n<td align=\"left\">Power input</td><td align=\"left\"><span class=\"Bold\">14 V DC, 1.1 A maximum</span></td>\n</tr>\n<tr>\n<td align=\"left\">Operating power consumption</td><td align=\"left\"><span class=\"Bold\">18 Watt maximum</span></td>\n</tr>\n<tr>\n<td align=\"left\">Ultrasonic frequency</td><td align=\"left\"><span class=\"Bold\">2.4 MHz (nominal)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Nebulization rate</td><td align=\"left\"><span class=\"Bold\">0.50 - 0.55 mg/min (0.9% Saline)</span></td>\n</tr>\n<tr>\n<td align=\"left\">Medicine cup capacity</td><td align=\"left\"><span class=\"Bold\">6 mL, nominal</span></td>\n</tr>\n<tr>\n<td align=\"left\">Water chamber capacity</td><td align=\"left\"><span class=\"Bold\">45 mL, nominal</span></td>\n</tr>\n<tr>\n<td align=\"left\">Electric protection class</td><td align=\"left\"><span class=\"Bold\">II, Type BF</span></td>\n</tr>\n<tr>\n<td align=\"left\">Storage temperature/humidity</td><td align=\"left\"><span class=\"Bold\">15 to 30ºC/20-80% relative humidity</span></td>\n</tr>\n<tr>\n<td align=\"left\">Operating temperature/humidity</td><td align=\"left\"><span class=\"Bold\">15 to 25ºC/40-75% relative humidity</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">A-weighted sound pressure level</td><td align=\"left\"><span class=\"Bold\">75 dBA (1 m), maximum</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="60%"> <col align="left" valign="top" width="60%"/> <col align="left" valign="top" width="40%"/> <thead> <tr class="First Last"> <th align="left" colspan="2">Packaging Dimensions (Approximate Length × Width × Height)</th> </tr> </thead> <tbody> <tr class="First"> <td align="left">Patient Starter Kit (PSK)</td><td align="left"><span class="Bold">13.0" × 12.4" × 9.2"</span></td> </tr> <tr> <td align="left">Monthly Refill Kit (MRK)</td><td align="left"><span class="Bold">11.8" × 8.2" × 3.0"</span></td> </tr> <tr class="Last"> <td align="left">Institutional Starter Kit (ISK)</td><td align="left"><span class="Bold">13.0" × 12.4" × 9.2"</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<col align=\"left\" valign=\"top\" width=\"60%\"/>\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" colspan=\"2\">Packaging Dimensions (Approximate Length × Width × Height)</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\">Patient Starter Kit (PSK)</td><td align=\"left\"><span class=\"Bold\">13.0\" × 12.4\" × 9.2\"</span></td>\n</tr>\n<tr>\n<td align=\"left\">Monthly Refill Kit (MRK)</td><td align=\"left\"><span class=\"Bold\">11.8\" × 8.2\" × 3.0\"</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">Institutional Starter Kit (ISK)</td><td align=\"left\"><span class=\"Bold\">13.0\" × 12.4\" × 9.2\"</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="60%"> <col align="left" valign="top" width="60%"/> <col align="left" valign="top" width="40%"/> <thead> <tr class="First Last"> <th align="left" colspan="2">TYVASO Mass and Particle Specifications for 9 breaths</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="2"> <dl class="Footnote"> <dt> <a href="#footnote-reference-6" name="footnote-6">*</a> </dt> <dd>n=108 data points from r=3 inhalation devices. Each data point was 9 breaths.</dd> <dt> <a href="#footnote-reference-7" name="footnote-7">†</a> </dt> <dd>n=216 data points from r=6 inhalation devices. Each data point was 1 breath.</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left">Mass Median Aerodynamic Diameter (MMAD)<a class="Sup" href="#footnote-6" name="footnote-reference-6">*</a></td><td align="left"><span class="Bold">mean = 2.0 µm<br/>SD = 0.3</span></td> </tr> <tr> <td align="left">Total Emitted Dose per Breath<a class="Sup" href="#footnote-7" name="footnote-reference-7">†</a></td><td align="left"><span class="Bold">mean = 6.0 µg<br/>SD = 0.4</span></td> </tr> <tr> <td align="left">Total Aerosol Mass<a class="Sup" href="#footnote-6">*</a></td><td align="left"><span class="Bold">mean = 58 µg<br/>SD = 5.9</span></td> </tr> <tr> <td align="left">Total Respirable Dose<a class="Sup" href="#footnote-6">*</a></td><td align="left"><span class="Bold">mean = 44.6 µg<br/>SD = 3.5</span></td> </tr> <tr> <td align="left">Respirable Fraction<a class="Sup" href="#footnote-6">*</a></td><td align="left"><span class="Bold">mean = 73%<br/>SD = 5</span></td> </tr> <tr class="Last"> <td align="left">Geometric Standard Deviation (GSD)<a class="Sup" href="#footnote-6">*</a></td><td align="left"><span class="Bold">mean = 2.6<br/>SD = 0.4</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<col align=\"left\" valign=\"top\" width=\"60%\"/>\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" colspan=\"2\">TYVASO Mass and Particle Specifications for 9 breaths</th>\n</tr>\n</thead>\n<tfoot>\n<tr>\n<td align=\"left\" colspan=\"2\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-6\" name=\"footnote-6\">*</a>\n</dt>\n<dd>n=108 data points from r=3 inhalation devices. Each data point was 9 breaths.</dd>\n<dt>\n<a href=\"#footnote-reference-7\" name=\"footnote-7\">†</a>\n</dt>\n<dd>n=216 data points from r=6 inhalation devices. Each data point was 1 breath.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\">Mass Median Aerodynamic Diameter (MMAD)<a class=\"Sup\" href=\"#footnote-6\" name=\"footnote-reference-6\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 2.0 µm<br/>SD = 0.3</span></td>\n</tr>\n<tr>\n<td align=\"left\">Total Emitted Dose per Breath<a class=\"Sup\" href=\"#footnote-7\" name=\"footnote-reference-7\">†</a></td><td align=\"left\"><span class=\"Bold\">mean = 6.0 µg<br/>SD = 0.4</span></td>\n</tr>\n<tr>\n<td align=\"left\">Total Aerosol Mass<a class=\"Sup\" href=\"#footnote-6\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 58 µg<br/>SD = 5.9</span></td>\n</tr>\n<tr>\n<td align=\"left\">Total Respirable Dose<a class=\"Sup\" href=\"#footnote-6\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 44.6 µg<br/>SD = 3.5</span></td>\n</tr>\n<tr>\n<td align=\"left\">Respirable Fraction<a class=\"Sup\" href=\"#footnote-6\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 73%<br/>SD = 5</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">Geometric Standard Deviation (GSD)<a class=\"Sup\" href=\"#footnote-6\">*</a></td><td align=\"left\"><span class=\"Bold\">mean = 2.6<br/>SD = 0.4</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="60%"> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="70%"/> <thead> <tr class="First Last"> <th align="left" colspan="2">Accessories</th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="2">Note: Part number subject to change.</td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left">TD-300N-US</td><td align="left"><span class="Bold">AC wall plug</span></td> </tr> <tr> <td align="left">TD-132</td><td align="left"><span class="Bold">Medicine cup, Quantity - 32</span></td> </tr> <tr> <td align="left">ON-109</td><td align="left"><span class="Bold">Filter membranes</span></td> </tr> <tr> <td align="left">ON-120/C</td><td align="left"><span class="Bold">Plugs</span></td> </tr> <tr> <td align="left">ON-101/C</td><td align="left"><span class="Bold">Filter shell</span></td> </tr> <tr> <td align="left">TD-103/C</td><td align="left"><span class="Bold">Dome assembly with baffle plate</span></td> </tr> <tr> <td align="left">ON-104/C</td><td align="left"><span class="Bold">Inhalation piece</span></td> </tr> <tr> <td align="left">ON-105/C</td><td align="left"><span class="Bold">Mouthpiece</span></td> </tr> <tr> <td align="left">TD-118</td><td align="left"><span class="Bold">Water level cup</span></td> </tr> <tr> <td align="left">TD-158</td><td align="left"><span class="Bold">Carrying case</span></td> </tr> <tr class="Last"> <td align="left">TD-155</td><td align="left"><span class="Bold">Distilled water carrier</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"60%\">\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"left\" valign=\"top\" width=\"70%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"left\" colspan=\"2\">Accessories</th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\">Note: Part number subject to change.</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"First\">\n<td align=\"left\">TD-300N-US</td><td align=\"left\"><span class=\"Bold\">AC wall plug</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-132</td><td align=\"left\"><span class=\"Bold\">Medicine cup, Quantity - 32</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-109</td><td align=\"left\"><span class=\"Bold\">Filter membranes</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-120/C</td><td align=\"left\"><span class=\"Bold\">Plugs</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-101/C</td><td align=\"left\"><span class=\"Bold\">Filter shell</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-103/C</td><td align=\"left\"><span class=\"Bold\">Dome assembly with baffle plate</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-104/C</td><td align=\"left\"><span class=\"Bold\">Inhalation piece</span></td>\n</tr>\n<tr>\n<td align=\"left\">ON-105/C</td><td align=\"left\"><span class=\"Bold\">Mouthpiece</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-118</td><td align=\"left\"><span class=\"Bold\">Water level cup</span></td>\n</tr>\n<tr>\n<td align=\"left\">TD-158</td><td align=\"left\"><span class=\"Bold\">Carrying case</span></td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\">TD-155</td><td align=\"left\"><span class=\"Bold\">Distilled water carrier</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">C: Electromagnetic compatibility (EMC)</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">C: Electromagnetic compatibility (EMC)</span></td>\n</tr>\n</tbody>\n</table></div>" }

The TYVASO Inhalation System has been tested and found to comply with the electromagnetic compatibility (EMC) limits for medical devices according to IEC 60601-1-2: (2007). Compliance is intended to provide reasonable protection against harmful interference in a typical user environment.

{ "type": "p", "children": [], "text": "The TYVASO Inhalation System has been tested and found to comply with the electromagnetic compatibility (EMC) limits for medical devices according to IEC 60601-1-2: (2007). Compliance is intended to provide reasonable protection against harmful interference in a typical user environment." }

Table 1, Table 2 and Table 3 document the intended EMC use environment and established compliance levels for the TYVASO Inhalation System. To ensure the intended performance, use the system in the environments described in these tables.

{ "type": "p", "children": [], "text": "Table 1, Table 2 and Table 3 document the intended EMC use environment and established compliance levels for the TYVASO Inhalation System. To ensure the intended performance, use the system in the environments described in these tables." }

The TYVASO Inhalation System is intended for use in the electromagnetic environment specified in this section.

{ "type": "p", "children": [], "text": "The TYVASO Inhalation System is intended for use in the electromagnetic environment specified in this section." }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Guidance and manufacturer's declaration - electromagnetic emissions</span> </caption> <col align="left" valign="top" width="15%"/> <col align="center" valign="top" width="15%"/> <col align="left" valign="top" width="70%"/> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Bold">Guidance and manufacturer's declaration - electromagnetic emissions</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3">The TYVASO Inhalation System is intended for use in the electromagnetic environment specified below. The customer or the user of the TYVASO Inhalation System should assure that it is used in such an environment.</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule"><span class="Bold">Emissions test</span></td><td align="center" class="Rrule"><span class="Bold">Compliance</span></td><td align="center" class="Rrule"><span class="Bold">Electromagnetic environment - guidance</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">RF emissions CISPR 11</td><td align="center" class="Rrule"><span class="Bold">Group 1</span></td><td align="left" class="Rrule">The TYVASO Inhalation System uses RF energy only for its internal function. Therefore, its RF emissions are very low and are not likely to cause any interference in nearby electronic equipment.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">RF emissions CISPR 11</td><td align="center" class="Rrule"><span class="Bold">Class B</span></td><td align="left" class="Rrule" rowspan="3">The TYVASO Inhalation System is suitable for use in all establishments, including domestic establishments and those directly connected to the public low voltage power supply network that supplies buildings used for domestic purposes.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Harmonic emissions IEC 61000-3-2</td><td align="center" class="Rrule"><span class="Bold">Class A</span></td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">Voltage fluctuations/flicker emissions IEC 61000-3-3</td><td align="center" class="Rrule"><span class="Bold">Complies</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 1: Guidance and manufacturer's declaration - electromagnetic emissions</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"15%\"/>\n<col align=\"center\" valign=\"top\" width=\"15%\"/>\n<col align=\"left\" valign=\"top\" width=\"70%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Guidance and manufacturer's declaration - electromagnetic emissions</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\">The TYVASO Inhalation System is intended for use in the electromagnetic environment specified below. The customer or the user of the TYVASO Inhalation System should assure that it is used in such an environment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">Emissions test</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Compliance</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Electromagnetic environment - guidance</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">RF emissions CISPR 11</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Group 1</span></td><td align=\"left\" class=\"Rrule\">The TYVASO Inhalation System uses RF energy only for its internal function. Therefore, its RF emissions are very low and are not likely to cause any interference in nearby electronic equipment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">RF emissions CISPR 11</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Class B</span></td><td align=\"left\" class=\"Rrule\" rowspan=\"3\">The TYVASO Inhalation System is suitable for use in all establishments, including domestic establishments and those directly connected to the public low voltage power supply network that supplies buildings used for domestic purposes.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Harmonic emissions IEC 61000-3-2</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Class A</span></td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\">Voltage fluctuations/flicker emissions IEC 61000-3-3</td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Complies</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2: Guidance and manufacturer's declaration – electromagnetic immunity</span> </caption> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="40%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4">NOTE: <span class="Italics">U</span><span class="Sub">T</span> is the a.c. mains voltage prior to application of the test level.<br/>NOTE 1: At 80 MHz and 800 MHz, the higher frequency range applies.<br/>NOTE 2: These guidelines may not apply in all situations. Electromagnetic propagation is affected by absorption and reflection from structures, objects and people.</td> </tr> <tr> <td align="left" colspan="4"> <dl class="Footnote"> <dt> <a href="#footnote-reference-8" name="footnote-8">*</a> </dt> <dd>Field strengths from fixed transmitters, such as base stations for radio (cellular/cordless) telephones and land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast cannot be predicted theoretically with accuracy. To assess the electromagnetic environment due to fixed RF transmitters, an electromagnetic site survey should be considered. If the measured field strength in the location in which the TYVASO Inhalation System is used exceeds the applicable RF compliance level above, the TYVASO Inhalation System should be observed to verify normal operation. If abnormal performance is observed, additional measures may be necessary, such as re-orienting or relocating the TYVASO Inhalation System.</dd> <dt> <a href="#footnote-reference-9" name="footnote-9">†</a> </dt> <dd>Over the frequency range 150 kHz to 80 MHz, field strengths should be less than [V1] V/m.</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="4"><span class="Bold">Guidance and manufacturer's declaration – electromagnetic immunity</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">The TYVASO Inhalation System is intended for use in the electromagnetic environment specified below. The customer or the user of the TYVASO Inhalation System should assure that it is used in such an environment.</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule"><span class="Bold">Immunity test</span></td><td align="center" class="Rrule"><span class="Bold">IEC 60601 Test level</span></td><td align="center" class="Rrule"><span class="Bold">Compliance level</span></td><td align="center" class="Rrule"><span class="Bold">Electromagnetic environment - guidance</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Electrostatic discharge (ESD)<br/>IEC 61000-4-2</td><td align="left" class="Rrule">± 8 kV contact<br/>± 15 kV air</td><td align="left" class="Rrule">± 8 kV contact<br/>± 15 kV air</td><td align="left" class="Rrule">Floors should be wood, concrete or ceramic tile. If floors are covered with synthetic material, the relative humidity should be at least 30%.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Electrical fast transient/burst<br/>IEC 61000-4-4</td><td align="left" class="Rrule">± 2 kV for power supply lines<br/>± 1 kV for input/output lines</td><td align="left" class="Rrule">± 2 kV for power supply lines<br/>± 1 kV for input/output lines</td><td align="left" class="Rrule">Mains power quality should be that of a typical commercial or hospital environment.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Surge<br/>IEC 61000-4-5</td><td align="left" class="Rrule">± 1 kV line(s) to line(s)<br/>± 2 kV line(s) to earth</td><td align="left" class="Rrule">± 1 kV line(s) to line(s)<br/>± 2 kV line(s) to earth</td><td align="left" class="Rrule">Mains power quality should be that of a typical commercial or hospital environment.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Voltage dips, short interruptions and voltage variations on power supply input lines<br/>IEC 61000-4-11</td><td align="left" class="Rrule"> 0 % <span class="Italics">U</span><span class="Sub">T</span> (100 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 0,5 cycle<br/> 0 % <span class="Italics">U</span><span class="Sub">T</span> (100 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 1 cycle<br/> 70 % <span class="Italics">U</span><span class="Sub">T</span> (30 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 25/30 cycles<br/> 0 % <span class="Italics">U</span><span class="Sub">T</span> (100 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 250/300 cycle</td><td align="left" class="Rrule"> 0 % <span class="Italics">U</span><span class="Sub">T</span> (100 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 0,5 cycle<br/> 0 % <span class="Italics">U</span><span class="Sub">T</span> (100 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 1 cycle<br/> 70 % <span class="Italics">U</span><span class="Sub">T</span> (30 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 25/30 cycles<br/> 0 % <span class="Italics">U</span><span class="Sub">T</span> (100 % dip in <span class="Italics">U</span><span class="Sub">T</span>) for 250/300 cycle</td><td align="left" class="Rrule">Mains power quality should be that of a typical commercial or hospital environment. If the user of the TYVASO Inhalation System requires continued operation during power mains interruptions, it is recommended that the TYVASO Inhalation System be powered from an uninterruptible power supply or the internal battery.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Power frequency (50/60 Hz) magnetic field<br/>IEC 61000-4-8</td><td align="left" class="Rrule">30 A/m</td><td align="left" class="Rrule">30 A/m</td><td align="left" class="Rrule">Power frequency magnetic fields should be at levels characteristic of a typical location in a typical commercial or hospital environment.</td> </tr> <tr class="Botrule Last"> <td align="left" class="Lrule Rrule">Conducted RF<br/>IEC 61000-4-6<br/>Radiated RF<br/>IEC 61000-4-3</td><td align="left" class="Rrule">3 Vrms 150 kHz to 80 MHz<br/>10 V/m 80 MHz to 2.6 GHz</td><td align="left" class="Rrule">3 Vrms 150 kHz to 80 MHz<br/>10 V/m 80 MHz to 2.6 GHz</td><td align="left" class="Rrule">Portable and mobile RF communications equipment should be used no closer to any part of TYVASO Inhalation System, including cables, than the recommended separation distance calculated from the equation applicable to the frequency of the transmitter.<br/> <span class="Bold">Recommended separation distance</span> <br/> <span class="Italics">d</span> = 1.2 √<span class="Italics">P</span> <br/> <span class="Italics">d</span> = 1.2 √<span class="Italics">P</span> 80 MHz to 800 MHz<br/> <span class="Italics">d</span> = 2.3 √<span class="Italics">P</span> 800 MHz to 2.5 GHz<br/>where <span class="Italics">P</span> is the maximum output power rating of the transmitter in watts (W) according to the transmitter manufacturer and <span class="Italics">d</span> is the recommended separation distance in meters (m).<br/>Field strengths from fixed RF transmitters, as determined by an electromagnetic site survey<a class="Sup" href="#footnote-8" name="footnote-reference-8">*</a>, should be less than the compliance level in each frequency range<a class="Sup" href="#footnote-9" name="footnote-reference-9">†</a>.<br/>Interference may occur in the vicinity of equipment marked with the following symbol: <img alt="Figure" src="/dailymed/image.cfm?name=tyvaso-233.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 2: Guidance and manufacturer's declaration – electromagnetic immunity</span>\n</caption>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"40%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"4\">NOTE: <span class=\"Italics\">U</span><span class=\"Sub\">T</span> is the a.c. mains voltage prior to application of the test level.<br/>NOTE 1: At 80 MHz and 800 MHz, the higher frequency range applies.<br/>NOTE 2: These guidelines may not apply in all situations. Electromagnetic propagation is affected by absorption and reflection from structures, objects and people.</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"4\">\n<dl class=\"Footnote\">\n<dt>\n<a href=\"#footnote-reference-8\" name=\"footnote-8\">*</a>\n</dt>\n<dd>Field strengths from fixed transmitters, such as base stations for radio (cellular/cordless) telephones and land mobile radios, amateur radio, AM and FM radio broadcast and TV broadcast cannot be predicted theoretically with accuracy. To assess the electromagnetic environment due to fixed RF transmitters, an electromagnetic site survey should be considered. If the measured field strength in the location in which the TYVASO Inhalation System is used exceeds the applicable RF compliance level above, the TYVASO Inhalation System should be observed to verify normal operation. If abnormal performance is observed, additional measures may be necessary, such as re-orienting or relocating the TYVASO Inhalation System.</dd>\n<dt>\n<a href=\"#footnote-reference-9\" name=\"footnote-9\">†</a>\n</dt>\n<dd>Over the frequency range 150 kHz to 80 MHz, field strengths should be less than [V1] V/m.</dd>\n</dl>\n</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Guidance and manufacturer's declaration – electromagnetic immunity</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">The TYVASO Inhalation System is intended for use in the electromagnetic environment specified below. The customer or the user of the TYVASO Inhalation System should assure that it is used in such an environment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">Immunity test</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">IEC 60601 Test level</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Compliance level</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">Electromagnetic environment - guidance</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Electrostatic discharge (ESD)<br/>IEC 61000-4-2</td><td align=\"left\" class=\"Rrule\">± 8 kV contact<br/>± 15 kV air</td><td align=\"left\" class=\"Rrule\">± 8 kV contact<br/>± 15 kV air</td><td align=\"left\" class=\"Rrule\">Floors should be wood, concrete or ceramic tile. If floors are covered with synthetic material, the relative humidity should be at least 30%.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Electrical fast transient/burst<br/>IEC 61000-4-4</td><td align=\"left\" class=\"Rrule\">± 2 kV for power supply lines<br/>± 1 kV for input/output lines</td><td align=\"left\" class=\"Rrule\">± 2 kV for power supply lines<br/>± 1 kV for input/output lines</td><td align=\"left\" class=\"Rrule\">Mains power quality should be that of a typical commercial or hospital environment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Surge<br/>IEC 61000-4-5</td><td align=\"left\" class=\"Rrule\">± 1 kV line(s) to line(s)<br/>± 2 kV line(s) to earth</td><td align=\"left\" class=\"Rrule\">± 1 kV line(s) to line(s)<br/>± 2 kV line(s) to earth</td><td align=\"left\" class=\"Rrule\">Mains power quality should be that of a typical commercial or hospital environment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Voltage dips, short interruptions and voltage variations on power supply input lines<br/>IEC 61000-4-11</td><td align=\"left\" class=\"Rrule\">\t\t\t\t\t\t\t\t\t0 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (100 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 0,5 cycle<br/>\t\t\t\t\t\t\t\t\t0 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (100 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 1 cycle<br/>\t\t\t\t\t\t\t\t\t70 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (30 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 25/30 cycles<br/>\t\t\t\t\t\t\t\t\t0 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (100 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 250/300 cycle</td><td align=\"left\" class=\"Rrule\">\t\t\t\t\t\t\t\t\t0 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (100 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 0,5 cycle<br/>\t\t\t\t\t\t\t\t\t0 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (100 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 1 cycle<br/>\t\t\t\t\t\t\t\t\t70 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (30 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 25/30 cycles<br/>\t\t\t\t\t\t\t\t\t0 % <span class=\"Italics\">U</span><span class=\"Sub\">T</span> (100 % dip in <span class=\"Italics\">U</span><span class=\"Sub\">T</span>) for 250/300 cycle</td><td align=\"left\" class=\"Rrule\">Mains power quality should be that of a typical commercial or hospital environment. If the user of the TYVASO Inhalation System requires continued operation during power mains interruptions, it is recommended that the TYVASO Inhalation System be powered from an uninterruptible power supply or the internal battery.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\">Power frequency (50/60 Hz) magnetic field<br/>IEC 61000-4-8</td><td align=\"left\" class=\"Rrule\">30 A/m</td><td align=\"left\" class=\"Rrule\">30 A/m</td><td align=\"left\" class=\"Rrule\">Power frequency magnetic fields should be at levels characteristic of a typical location in a typical commercial or hospital environment.</td>\n</tr>\n<tr class=\"Botrule Last\">\n<td align=\"left\" class=\"Lrule Rrule\">Conducted RF<br/>IEC 61000-4-6<br/>Radiated RF<br/>IEC 61000-4-3</td><td align=\"left\" class=\"Rrule\">3 Vrms 150 kHz to 80 MHz<br/>10 V/m 80 MHz to 2.6 GHz</td><td align=\"left\" class=\"Rrule\">3 Vrms 150 kHz to 80 MHz<br/>10 V/m 80 MHz to 2.6 GHz</td><td align=\"left\" class=\"Rrule\">Portable and mobile RF communications equipment should be used no closer to any part of TYVASO Inhalation System, including cables, than the recommended separation distance calculated from the equation applicable to the frequency of the transmitter.<br/>\n<span class=\"Bold\">Recommended separation distance</span>\n<br/>\n<span class=\"Italics\">d</span> = 1.2 √<span class=\"Italics\">P</span>\n<br/>\n<span class=\"Italics\">d</span> = 1.2 √<span class=\"Italics\">P</span> 80 MHz to 800 MHz<br/>\n<span class=\"Italics\">d</span> = 2.3 √<span class=\"Italics\">P</span> 800 MHz to 2.5 GHz<br/>where <span class=\"Italics\">P</span> is the maximum output power rating of the transmitter in watts (W) according to the transmitter manufacturer and <span class=\"Italics\">d</span> is the recommended separation distance in meters (m).<br/>Field strengths from fixed RF transmitters, as determined by an electromagnetic site survey<a class=\"Sup\" href=\"#footnote-8\" name=\"footnote-reference-8\">*</a>, should be less than the compliance level in each frequency range<a class=\"Sup\" href=\"#footnote-9\" name=\"footnote-reference-9\">†</a>.<br/>Interference may occur in the vicinity of equipment marked with the following symbol: <img alt=\"Figure\" src=\"/dailymed/image.cfm?name=tyvaso-233.jpg&amp;setid=cbc31ab1-a80f-4b50-a3b1-39910b0fb609\"/></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Manufacturer's Declaration – Recommended separation distances between portable and mobile communications equipment and the TYVASO Inhalation System</span> </caption> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="4">For transmitters rated at a maximum output power not listed above, the recommended separation distance <span class="Italics">d</span> in meters (m) can be estimated using the equation applicable to the frequency of the transmitter, where <span class="Italics">P</span> is the maximum output power rating of the transmitter in watts (W) according to the transmitter manufacturer.<br/> NOTE 1: At 80 MHz and 800 MHz, the separation distance for the higher frequency range applies.<br/> NOTE 2: These guidelines may not apply in all situations. Electromagnetic propagation is affected by absorption and reflection from structures, objects and people.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="4"><span class="Bold">Recommended separation distances between portable and mobile RF communications equipment and the TYVASO Inhalation System</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="4">The TYVASO Inhalation System is intended for use in an electromagnetic environment in which radiated RF disturbances are controlled. The customer or the user of the TYVASO Inhalation System can help prevent electromagnetic interference by maintaining a minimum distance between portable and mobile RF communications equipment (transmitters) and the TYVASO Inhalation System as recommended below, according to the maximum output power of the communications equipment.</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" rowspan="2"><span class="Bold">Rated maximum output power of transmitter</span> <br/>W</td><td align="center" class="Rrule" colspan="3"><span class="Bold">Separation distance according to frequency of transmitter</span> <br/>m</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule"><span class="Bold">150 kHz to 80 MHz</span> <br/> <span class="Italics">d</span> = 1.2 √<span class="Italics">P</span></td><td align="center" class="Rrule"><span class="Bold">80 MHz to 800 MHz</span> <br/> <span class="Italics">d</span> = 1.2 √<span class="Italics">P</span></td><td align="center" class="Rrule"><span class="Bold">800 MHz to 2.5 GHz</span> <br/> <span class="Italics">d</span> = 2.3 √<span class="Italics">P</span></td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">0.01</td><td align="center" class="Rrule">0.12</td><td align="center" class="Rrule">0.12</td><td align="center" class="Rrule">0.23</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">0.1</td><td align="center" class="Rrule">0.38</td><td align="center" class="Rrule">0.38</td><td align="center" class="Rrule">0.73</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">1</td><td align="center" class="Rrule">1.2</td><td align="center" class="Rrule">1.2</td><td align="center" class="Rrule">2.3</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">10</td><td align="center" class="Rrule">3.8</td><td align="center" class="Rrule">3.8</td><td align="center" class="Rrule">7.3</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">100</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">12</td><td align="center" class="Rrule">23</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<caption>\n<span>Table 3: Manufacturer's Declaration – Recommended separation distances between portable and mobile communications equipment and the TYVASO Inhalation System</span>\n</caption>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"4\">For transmitters rated at a maximum output power not listed above, the recommended separation distance <span class=\"Italics\">d</span> in meters (m) can be estimated using the equation applicable to the frequency of the transmitter, where <span class=\"Italics\">P</span> is the maximum output power rating of the transmitter in watts (W) according to the transmitter manufacturer.<br/> NOTE 1: At 80 MHz and 800 MHz, the separation distance for the higher frequency range applies.<br/> NOTE 2: These guidelines may not apply in all situations. Electromagnetic propagation is affected by absorption and reflection from structures, objects and people.</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"4\"><span class=\"Bold\">Recommended separation distances between portable and mobile RF communications equipment and the TYVASO Inhalation System</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"4\">The TYVASO Inhalation System is intended for use in an electromagnetic environment in which radiated RF disturbances are controlled. The customer or the user of the TYVASO Inhalation System can help prevent electromagnetic interference by maintaining a minimum distance between portable and mobile RF communications equipment (transmitters) and the TYVASO Inhalation System as recommended below, according to the maximum output power of the communications equipment.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" rowspan=\"2\"><span class=\"Bold\">Rated maximum output power of transmitter</span>\n<br/>W</td><td align=\"center\" class=\"Rrule\" colspan=\"3\"><span class=\"Bold\">Separation distance according to frequency of transmitter</span>\n<br/>m</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\"><span class=\"Bold\">150 kHz to 80 MHz</span>\n<br/>\n<span class=\"Italics\">d</span> = 1.2 √<span class=\"Italics\">P</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">80 MHz to 800 MHz</span>\n<br/>\n<span class=\"Italics\">d</span> = 1.2 √<span class=\"Italics\">P</span></td><td align=\"center\" class=\"Rrule\"><span class=\"Bold\">800 MHz to 2.5 GHz</span>\n<br/>\n<span class=\"Italics\">d</span> = 2.3 √<span class=\"Italics\">P</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">0.01</td><td align=\"center\" class=\"Rrule\">0.12</td><td align=\"center\" class=\"Rrule\">0.12</td><td align=\"center\" class=\"Rrule\">0.23</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">0.1</td><td align=\"center\" class=\"Rrule\">0.38</td><td align=\"center\" class=\"Rrule\">0.38</td><td align=\"center\" class=\"Rrule\">0.73</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">1</td><td align=\"center\" class=\"Rrule\">1.2</td><td align=\"center\" class=\"Rrule\">1.2</td><td align=\"center\" class=\"Rrule\">2.3</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\">10</td><td align=\"center\" class=\"Rrule\">3.8</td><td align=\"center\" class=\"Rrule\">3.8</td><td align=\"center\" class=\"Rrule\">7.3</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Lrule Rrule\">100</td><td align=\"center\" class=\"Rrule\">12</td><td align=\"center\" class=\"Rrule\">12</td><td align=\"center\" class=\"Rrule\">23</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">D: Glossary</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<tbody class=\"Headless\">\n<tr class=\"Botrule\">\n<td align=\"left\"><span class=\"Bold\">D: Glossary</span></td>\n</tr>\n</tbody>\n</table></div>" }

Accessories: Parts of the TYVASO Inhalation System. See page 29.

{ "type": "p", "children": [], "text": "\nAccessories: Parts of the TYVASO Inhalation System. See page 29." }

Ampule: A sealed, lightweight clear plastic vial containing a 1-day supply of TYVASO® (treprostinil) Inhalation Solution.

{ "type": "p", "children": [], "text": "\nAmpule: A sealed, lightweight clear plastic vial containing a 1-day supply of TYVASO® (treprostinil) Inhalation Solution." }

Black ring: A round seal that fits on the bottom of the dome assembly. The seal helps ensure that TYVASO does not mix with the distilled water in the device water chamber.

{ "type": "p", "children": [], "text": "\nBlack ring: A round seal that fits on the bottom of the dome assembly. The seal helps ensure that TYVASO does not mix with the distilled water in the device water chamber." }

Display screen: A small area on the inhalation device that provides instructions and device information.

{ "type": "p", "children": [], "text": "\nDisplay screen: A small area on the inhalation device that provides instructions and device information." }

Distilled water: Water that is highly purified so that it contains only essential elements.

{ "type": "p", "children": [], "text": "\nDistilled water: Water that is highly purified so that it contains only essential elements." }

Dome assembly: The plastic accessory that contains the baffle plate and connects the mouthpiece, inhalation piece, and filter shells to the base of the inhalation device.

{ "type": "p", "children": [], "text": "\nDome assembly: The plastic accessory that contains the baffle plate and connects the mouthpiece, inhalation piece, and filter shells to the base of the inhalation device." }

Filter membrane: The white pad that goes into the filter shells.

{ "type": "p", "children": [], "text": "\nFilter membrane: The white pad that goes into the filter shells." }

Filter shells: Plastic accessories that hold the filter membranes.

{ "type": "p", "children": [], "text": "\nFilter shells: Plastic accessories that hold the filter membranes." }

Inhalation indicator lights: Two green lights on the top surface of the inhalation device that signals when you should inhale.

{ "type": "p", "children": [], "text": "\nInhalation indicator lights: Two green lights on the top surface of the inhalation device that signals when you should inhale." }

Inhalation piece: The plastic accessory that connects the mouthpiece with the dome assembly.

{ "type": "p", "children": [], "text": "\nInhalation piece: The plastic accessory that connects the mouthpiece with the dome assembly." }

Inhalation device: The base of the TYVASO Inhalation System to which the accessories connect. The inhalation device contains the display screen and lights.

{ "type": "p", "children": [], "text": "\nInhalation device: The base of the TYVASO Inhalation System to which the accessories connect. The inhalation device contains the display screen and lights." }

Inhale: How you will breathe in TYVASO with the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nInhale: How you will breathe in TYVASO with the TYVASO Inhalation System." }

Medicine cup: The disposable plastic cone-shaped cup into which TYVASO is poured. The medicine cup fits inside the water chamber.

{ "type": "p", "children": [], "text": "\nMedicine cup: The disposable plastic cone-shaped cup into which TYVASO is poured. The medicine cup fits inside the water chamber." }

Mouthpiece: The plastic part that you will breathe through (using your mouth) to inhale TYVASO.

{ "type": "p", "children": [], "text": "\nMouthpiece: The plastic part that you will breathe through (using your mouth) to inhale TYVASO." }

On/Off, Start/Pause (blue) button: A manually activated control on the front of the device that switches between fully on and fully off power states. Once the device power is on, the button begins or pauses treatment.

{ "type": "p", "children": [], "text": "\nOn/Off, Start/Pause (blue) button: A manually activated control on the front of the device that switches between fully on and fully off power states. Once the device power is on, the button begins or pauses treatment." }

Plugs: Plastic accessories that are inserted into the openings of the dome assembly between treatment sessions. Plugs help keep TYVASO from spilling if the inhalation device tips over.

{ "type": "p", "children": [], "text": "\nPlugs: Plastic accessories that are inserted into the openings of the dome assembly between treatment sessions. Plugs help keep TYVASO from spilling if the inhalation device tips over." }

Power status light: LED on the back of the device that lights green when power is connected and battery is charging.

{ "type": "p", "children": [], "text": "\nPower status light: LED on the back of the device that lights green when power is connected and battery is charging." }

Power port: Port on back of device for plugging into a power source using the AC wall plug.

{ "type": "p", "children": [], "text": "\nPower port: Port on back of device for plugging into a power source using the AC wall plug." }

Prompts: The audio and visual signals that help guide you through the treatment sessions.

{ "type": "p", "children": [], "text": "\nPrompts: The audio and visual signals that help guide you through the treatment sessions." }

Run / Program switch: A manually activated control on the side of the device that switches between the modes for delivering treatment (Run) and programming breaths (Program).

{ "type": "p", "children": [], "text": "\nRun / Program switch: A manually activated control on the side of the device that switches between the modes for delivering treatment (Run) and programming breaths (Program)." }

Sensors: The silver objects on the inside wall of the water chamber. The sensors must be covered with distilled water for the TYVASO Inhalation System to function properly.

{ "type": "p", "children": [], "text": "\nSensors: The silver objects on the inside wall of the water chamber. The sensors must be covered with distilled water for the TYVASO Inhalation System to function properly." }

Specialty pharmacy provider: A pharmacy that carries only specialized medicines and medical devices. Your specialty pharmacy provider is a good source of information about TYVASO and the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nSpecialty pharmacy provider: A pharmacy that carries only specialized medicines and medical devices. Your specialty pharmacy provider is a good source of information about TYVASO and the TYVASO Inhalation System." }

Treatment session: 1 of 4 daily sessions during which you will take TYVASO with a specific number of inhalations.

{ "type": "p", "children": [], "text": "\nTreatment session: 1 of 4 daily sessions during which you will take TYVASO with a specific number of inhalations." }

TYVASO: The prescription medicine that you will use with the TYVASO Inhalation System.

{ "type": "p", "children": [], "text": "\nTYVASO: The prescription medicine that you will use with the TYVASO Inhalation System." }

Volume / Breaths toggle button: A manually activated control on the side of the device that increases or decreases audio volume (when in Run mode) and programmed breaths (when in Program mode).

{ "type": "p", "children": [], "text": "\nVolume / Breaths toggle button: A manually activated control on the side of the device that increases or decreases audio volume (when in Run mode) and programmed breaths (when in Program mode)." }

Water chamber: The white hollow portion in the center of the inhalation device into which distilled water and the medicine cup are placed.

{ "type": "p", "children": [], "text": "\nWater chamber: The white hollow portion in the center of the inhalation device into which distilled water and the medicine cup are placed." }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <tbody class="Headless"> <tr class="Botrule"> <td align="left"><span class="Bold">E: Warranty information</span></td> </tr> </tbody> </table></div>

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Your TYVASO Inhalation System is granted a replacement or repair warranty good for 2 years from your date of receipt of the TYVASO Inhalation System or 5 years from the date of manufacture, whichever comes first. This warranty applies to the TYVASO Inhalation System device only. Accessory components are not covered under warranty.

{ "type": "p", "children": [], "text": "\nYour TYVASO Inhalation System is granted a replacement or repair warranty good for 2 years from your date of receipt of the TYVASO Inhalation System or 5 years from the date of manufacture, whichever comes first. This warranty applies to the TYVASO Inhalation System device only. Accessory components are not covered under warranty.\n" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">Circumstances that may void your warranty include:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">▶ Modification or disassembly of the TYVASO Inhalation System device by anyone other than a factory-authorized technician</td> </tr> <tr class="Botrule"> <td align="left">▶ Failure to comply with this written Instructions for Use manual when operating the TYVASO Inhalation System</td> </tr> <tr class="Botrule"> <td align="left">▶ Unapproved use of the TYVASO Inhalation System</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">Circumstances that may void your warranty include:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Modification or disassembly of the TYVASO Inhalation System device by anyone other than a factory-authorized technician</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Failure to comply with this written Instructions for Use manual when operating the TYVASO Inhalation System</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Unapproved use of the TYVASO Inhalation System</td>\n</tr>\n</tbody>\n</table></div>" }

For all inquiries relating to service or warranty for your TYVASO Inhalation System, contact your specialty pharmacy provider.

{ "type": "p", "children": [], "text": "\nFor all inquiries relating to service or warranty for your TYVASO Inhalation System, contact your specialty pharmacy provider.\n" }

<div class="scrollingtable"><table class="Noautorules" width="50%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">You should have the following information available:</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">▶ Device serial number (located on bottom of TYVASO Inhalation System)</td> </tr> <tr class="Botrule"> <td align="left">▶ Date TYVASO Inhalation System was acquired</td> </tr> <tr class="Botrule"> <td align="left">▶ Nature of the problem and any steps taken to fix it</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"50%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">You should have the following information available:</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Device serial number (located on bottom of TYVASO Inhalation System)</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Date TYVASO Inhalation System was acquired</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Nature of the problem and any steps taken to fix it</td>\n</tr>\n</tbody>\n</table></div>" }

TYVASO ® INHALATION SYSTEM

{ "type": "p", "children": [], "text": "\nTYVASO ®\n\nINHALATION SYSTEM\n" }

TYVASO® (treprostinil) INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "\nTYVASO®\n\n(treprostinil)\nINHALATIONSOLUTION\n" }

TYVASO Inhalation Solution is for prescription use only.

{ "type": "p", "children": [], "text": "\nTYVASO Inhalation Solution is for prescription use only.\n" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <col align="left" valign="bottom" width="100%"/> <thead> <tr> <th align="left">Emergency contact information</th> </tr> </thead> <tbody> <tr class="Botrule"> <td align="left">▶ Clinician:</td> </tr> <tr class="Botrule"> <td align="left">▶ Nurse educator:</td> </tr> <tr class="Botrule"> <td align="left">▶ Specialty pharmacist:</td> </tr> <tr class="Botrule"> <td align="left">▶ United Therapeutics:</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<col align=\"left\" valign=\"bottom\" width=\"100%\"/>\n<thead>\n<tr>\n<th align=\"left\">Emergency contact information</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Clinician:</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Nurse educator:</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ Specialty pharmacist:</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\">▶ United Therapeutics:</td>\n</tr>\n</tbody>\n</table></div>" }

For further questions and information, or to report a problem with your device or an adverse event with your TYVASO Inhalation System, please call 1-877-UNITHER (1-877-864-8437).

{ "type": "p", "children": [], "text": "\nFor further questions and information, or to report a problem with your device or an adverse event with your TYVASO Inhalation System, please call 1-877-UNITHER (1-877-864-8437).\n" }

Distributed by: United Therapeutics CorporationResearch Triangle Park, North Carolina 27709

{ "type": "p", "children": [], "text": "\nDistributed by:\nUnited Therapeutics CorporationResearch Triangle Park, North Carolina 27709" }

© 2024, United Therapeutics Corporation.All rights reserved.

{ "type": "p", "children": [], "text": "© 2024, United Therapeutics Corporation.All rights reserved." }

102131

{ "type": "p", "children": [], "text": "\n102131\n" }

TYVASO is a registered trademark ofUnited Therapeutics Corporation.

{ "type": "p", "children": [], "text": "TYVASO is a registered trademark ofUnited Therapeutics Corporation." }

This Instructions for Use has beenapproved by the U.S. Food and DrugAdministration.

{ "type": "p", "children": [], "text": "This Instructions for Use has beenapproved by the U.S. Food and DrugAdministration." }

Revised: January 2024

{ "type": "p", "children": [], "text": "Revised: January 2024" }

TYVASO® (treprostinil) INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "\t\t\t\t\t\t\tTYVASO®\n\t\t\t\t\t\t\t(treprostinil) \t\t\t\t\t\t\t\t\t\t\t\t\t\tINHALATIONSOLUTION \t\t\t\t\t\t" }

Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL)

{ "type": "p", "children": [], "text": "Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL)" }

Four 2.9 mL ampules

{ "type": "p", "children": [], "text": "Four 2.9 mL ampules" }

For oral inhalation use only

{ "type": "p", "children": [], "text": "\t\t\t\t\t\t\tFor oral inhalation use only \t\t\t\t\t\t" }

See package insert andInstructions For Use manualfor dosage and administration

{ "type": "p", "children": [], "text": "See package insert andInstructions For Use manualfor dosage and administration" }

TYVASO® (treprostinil) INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "\nTYVASO®\n\n(treprostinil)\n\nINHALATIONSOLUTION\n" }

Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL)

{ "type": "p", "children": [], "text": "Treprostinil 1.74 mg / 2.9 mL (0.6 mg/mL)" }

Seven foil pouches each containing four2.9 mL ampules

{ "type": "p", "children": [], "text": "Seven foil pouches each containing four2.9 mL ampules" }

For oral inhalation use only

{ "type": "p", "children": [], "text": "\t\t\t\t\t\t\tFor oral inhalation use only \t\t\t\t\t\t" }

See package insert andInstructions For Use manualfor dosage and administration.

{ "type": "p", "children": [], "text": "See package insert andInstructions For Use manualfor dosage and administration." }

TYVASO Inhalation System

{ "type": "p", "children": [], "text": "TYVASO Inhalation System" }

Patient Starter Kit

{ "type": "p", "children": [], "text": "Patient Starter Kit" }

TYVASO® (treprostinil)INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "TYVASO®\n(treprostinil)INHALATIONSOLUTION" }

Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)

{ "type": "p", "children": [], "text": "Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)" }

TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System.See package insert and Instructions for Use manual for dosage and administration.

{ "type": "p", "children": [], "text": "TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System.See package insert and Instructions for Use manual for dosage and administration." }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="middle" width="44%"/> <col align="center" valign="middle" width="8%"/> <col align="left" valign="middle" width="40%"/> <col align="center" valign="middle" width="8%"/> <tbody class="Headless"> <tr> <td align="left">CONTENTS</td><td align="center">QTY</td><td align="left">CONTENTS</td><td align="center">QTY</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>28 ampule carton of TYVASO<br/>(seven foil pouches, each containing four 2.9 mL ampules)</dd> </dl> </td><td align="center">1</td><td align="left"> <dl> <dt>+</dt> <dd>AC wall plugs</dd> </dl> </td><td align="center">2</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>TYVASO Inhalation Device</dd> </dl> </td><td align="center">2</td><td align="left"> <dl> <dt>+</dt> <dd>Water level cup</dd> </dl> </td><td align="center">1</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>TYVASO Inhalation System Instructions for Use manual</dd> </dl> </td><td align="center">1</td><td align="left"> <dl> <dt>+</dt> <dd>Plugs for storage between treatment sessions</dd> </dl> </td><td align="center">2</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Treatment Tracker</dd> </dl> </td><td align="center">1</td><td align="left"> <dl> <dt>+</dt> <dd>Carrying case</dd> </dl> </td><td align="center">1</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Sets of Dome assembly, Inhalation piece,<br/>Mouthpiece, and 2 Filter shells</dd> </dl> </td><td align="center">2</td><td align="left"> <dl> <dt>+</dt> <dd>Distilled water carrier</dd> </dl> </td><td align="center">1</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Medicine cups</dd> </dl> </td><td align="center">32</td><td align="left"> <dl> <dt>+</dt> <dd>Filter membranes</dd> </dl> </td><td align="center">65</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"middle\" width=\"44%\"/>\n<col align=\"center\" valign=\"middle\" width=\"8%\"/>\n<col align=\"left\" valign=\"middle\" width=\"40%\"/>\n<col align=\"center\" valign=\"middle\" width=\"8%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\">CONTENTS</td><td align=\"center\">QTY</td><td align=\"left\">CONTENTS</td><td align=\"center\">QTY</td>\n</tr>\n<tr>\n<td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>28 ampule carton of TYVASO<br/>(seven foil pouches, each containing four 2.9 mL ampules)</dd>\n</dl>\n</td><td align=\"center\">1</td><td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>AC wall plugs</dd>\n</dl>\n</td><td align=\"center\">2</td>\n</tr>\n<tr>\n<td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>TYVASO Inhalation Device</dd>\n</dl>\n</td><td align=\"center\">2</td><td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Water level cup</dd>\n</dl>\n</td><td align=\"center\">1</td>\n</tr>\n<tr>\n<td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>TYVASO Inhalation System Instructions for Use manual</dd>\n</dl>\n</td><td align=\"center\">1</td><td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Plugs for storage between treatment sessions</dd>\n</dl>\n</td><td align=\"center\">2</td>\n</tr>\n<tr>\n<td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Treatment Tracker</dd>\n</dl>\n</td><td align=\"center\">1</td><td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Carrying case</dd>\n</dl>\n</td><td align=\"center\">1</td>\n</tr>\n<tr>\n<td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Sets of Dome assembly, Inhalation piece,<br/>Mouthpiece, and 2 Filter shells</dd>\n</dl>\n</td><td align=\"center\">2</td><td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Distilled water carrier</dd>\n</dl>\n</td><td align=\"center\">1</td>\n</tr>\n<tr>\n<td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Medicine cups</dd>\n</dl>\n</td><td align=\"center\">32</td><td align=\"left\">\n<dl>\n<dt>+</dt>\n<dd>Filter membranes</dd>\n</dl>\n</td><td align=\"center\">65</td>\n</tr>\n</tbody>\n</table></div>" }

Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.Hydrochloric acid and sodium hydroxide may have been added to adjust pH.

{ "type": "p", "children": [], "text": "Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.Hydrochloric acid and sodium hydroxide may have been added to adjust pH." }

{ "type": "", "children": [], "text": "" }

Patient Starter Kit For Single Patient Use Only. Keep out of the reach of children.NDC 66302-206-01 Rx only

{ "type": "p", "children": [], "text": "Patient Starter Kit For Single Patient Use Only.\t\t\t\t\t\tKeep out of the reach of children.NDC 66302-206-01 Rx only \t\t\t\t\t\t" }

Manufactured by United Therapeutics CorporationResearch Triangle Park, NC 27709

{ "type": "p", "children": [], "text": "Manufactured by United Therapeutics CorporationResearch Triangle Park, NC 27709" }

UnitedTherapeuticsCORPORATION

{ "type": "p", "children": [], "text": "UnitedTherapeuticsCORPORATION" }

102129 Rev. 01/2024

{ "type": "p", "children": [], "text": "102129 Rev. 01/2024" }

TYVASO Inhalation SystemRefill Kit

{ "type": "p", "children": [], "text": "TYVASO Inhalation SystemRefill Kit" }

TYVASO® (treprostinil)INHALATIONSOLUTION

{ "type": "p", "children": [], "text": "TYVASO®\n(treprostinil)INHALATIONSOLUTION" }

Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)

{ "type": "p", "children": [], "text": "Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)" }

TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System.See package insert and Instructions for Use manual for dosage and administration.

{ "type": "p", "children": [], "text": "TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System.See package insert and Instructions for Use manual for dosage and administration." }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="middle" width="44%"/> <col align="center" valign="middle" width="8%"/> <col align="left" valign="middle" width="40%"/> <col align="center" valign="middle" width="8%"/> <tbody class="Headless"> <tr> <td align="left">CONTENTS</td><td align="center">QTY</td><td align="left">CONTENTS</td><td align="center">QTY</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>28 ampule carton of TYVASO<br/>(seven foil pouches each containing four 2.9 mL ampules)</dd> </dl> </td><td align="center"> 1 </td><td align="left"> <dl> <dt>+</dt> <dd>Filter membranes</dd> </dl> </td><td align="center"> 65 </td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Set of Dome assembly, Inhalation piece,<br/>Mouthpiece, and 2 Filter shells</dd> </dl> </td><td align="center"> 1 </td><td align="left"> <dl> <dt>+</dt> <dd>Plugs for storage between treatment sessions</dd> </dl> </td><td align="center"> 2 </td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Medicine cups</dd> </dl> </td><td align="center"> 32 </td><td align="left"> <dl> <dt>+</dt> <dd>Treatment Tracker</dd> </dl> </td><td align="center"> 1 </td> </tr> </tbody> </table></div>

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Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.Hydrochloric acid and sodium hydroxide may have been added to adjust pH.

{ "type": "p", "children": [], "text": "Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.Hydrochloric acid and sodium hydroxide may have been added to adjust pH." }

{ "type": "", "children": [], "text": "" }

Keep out of the reach of children.

{ "type": "p", "children": [], "text": "Keep out of the reach of children." }

NDC 66302-206-02Rx only

{ "type": "p", "children": [], "text": "NDC 66302-206-02Rx only" }

Manufactured for United Therapeutics CorporationResearch Triangle Park, NC 27709

{ "type": "p", "children": [], "text": "Manufactured for United Therapeutics CorporationResearch Triangle Park, NC 27709" }

UnitedTherapeuticsCORPORATION

{ "type": "p", "children": [], "text": "UnitedTherapeuticsCORPORATION" }

102136Rev. 01/2024

{ "type": "p", "children": [], "text": "102136Rev. 01/2024" }

LOT XXXXXXXEXP YYYY-MMMGTIN XXXXXXXXXXXXXXS/N XXXXXXXXXXXX

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TYVASO Inhalation SystemInstitutional Starter Kit

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TYVASO® (treprostinil)INHALATIONSOLUTION

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Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)

{ "type": "p", "children": [], "text": "Treprostinil 1.74 mg/2.9 mL (0.6 mg/mL)" }

TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System.See package insert and Instructions for Use manual for dosage and administration.

{ "type": "p", "children": [], "text": "TYVASO is for oral inhalation use only and is intended for administration with the TYVASO Inhalation System.See package insert and Instructions for Use manual for dosage and administration." }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="middle" width="42%"/> <col align="center" valign="middle" width="8%"/> <col align="left" valign="middle" width="42%"/> <col align="center" valign="middle" width="8%"/> <tbody class="Headless"> <tr> <td align="left">CONTENTS</td><td align="center">QTY</td><td align="left">CONTENTS</td><td align="center">QTY</td> </tr> <tr> <td align="left" valign="middle"> <dl> <dt>+</dt> <dd>4 ampule carton of TYVASO<br/>(one foil pouch containing four 2.9 mL ampules)</dd> </dl> </td><td align="center">1</td><td align="left"> <dl> <dt>+</dt> <dd>AC wall plugs</dd> </dl> </td><td align="center">2</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>TYVASO Inhalation Device</dd> </dl> </td><td align="center">2</td><td align="left"> <dl> <dt>+</dt> <dd>Water level cup</dd> </dl> </td><td align="center">1</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>TYVASO Inhalation System Instructions for Use manual</dd> </dl> </td><td align="center">1</td><td align="left"> <dl> <dt>+</dt> <dd>Plugs for storage between treatment sessions</dd> </dl> </td><td align="center">2</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Treatment Tracker</dd> </dl> </td><td align="center">1</td><td align="left"> <dl> <dt>+</dt> <dd>Carrying case</dd> </dl> </td><td align="center">1</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Sets of Dome assembly, Inhalation piece,<br/>Mouthpiece, and 2 Filter shells</dd> </dl> </td><td align="center">2</td><td align="left"> <dl> <dt>+</dt> <dd>Distilled water carrier</dd> </dl> </td><td align="center">1</td> </tr> <tr> <td align="left"> <dl> <dt>+</dt> <dd>Medicine cups</dd> </dl> </td><td align="center">32</td><td align="left"> <dl> <dt>+</dt> <dd>Filter membranes</dd> </dl> </td><td align="center">65</td> </tr> </tbody> </table></div>

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Each ampule of TYVASO contains: treprostinil 1.74 mg. Each ampule also contains 18.9 mg sodium chloride,18.3 mg sodium citrate dihydrate, 0.6 mg sodium hydroxide, 11.7 mg 1N hydrochloric acid, and water for injection.Hydrochloric acid and sodium hydroxide may have been added to adjust pH.

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Institutional Starter Kit For Single Patient Use Only. Keep out of the reach of children.NDC 66302-206-04 Rx only

{ "type": "p", "children": [], "text": "Institutional Starter Kit For Single Patient Use Only.\t\t\t\t\t\tKeep out of the reach of children.NDC 66302-206-04 Rx only" }

Manufactured by United Therapeutics CorporationResearch Triangle Park, NC 27709

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UnitedTherapeuticsCORPORATION

{ "type": "p", "children": [], "text": "UnitedTherapeuticsCORPORATION" }

102130Rev. 01/2024

{ "type": "p", "children": [], "text": "102130Rev. 01/2024" }

Tyvaso DPI is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies with Tyvaso establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).

The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

While there are long-term data on use of treprostinil by other routes of administration, nearly all clinical experience with inhaled treprostinil has been on a background of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor. The controlled clinical experience with Tyvaso was limited to 12 weeks in duration [see Clinical Studies (14)].

Tyvaso DPI is indicated for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study with Tyvaso establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%) [see Clinical Studies (14.3)].

Use Tyvaso DPI only with the Tyvaso DPI Inhaler. Tyvaso DPI is administered using a single inhalation per cartridge. Administer Tyvaso DPI in 4 separate, equally spaced treatment sessions per day, during waking hours. The treatment sessions should be approximately 4 hours apart.

If the prescribed dose is higher than 80 mcg per treatment session, more than 1 cartridge will be needed per session. Patients should follow the instructions for use for operation and care of the Tyvaso DPI Inhaler.

Do not use the Tyvaso DPI Inhaler with other medications.

Between each of the 4 daily treatment sessions, store the Tyvaso DPI Inhaler with the mouthpiece attached and empty. Wipe the outside of the inhaler with a clean, dry cloth only, if needed. Do not rinse or wash the Tyvaso DPI Inhaler; always keep the inhaler dry. After 7 days of use, throw away the used Tyvaso DPI Inhaler into regular household trash.

Initial Dosage:

Tyvaso DPI therapy should begin with one 16 mcg cartridge per treatment session, 4 times daily.

Maintenance Dosage:

Increase dosage by an additional 16 mcg per treatment session at approximately 1- to 2-week intervals. The target maintenance dosage is usually 48 mcg to 64 mcg per session.

If adverse effects preclude titration, continue Tyvaso DPI at the highest tolerated dose.

If a scheduled treatment session is missed, resume therapy as soon as possible at the usual dose.

Dosage for Transition from Tyvaso® (treprostinil) Inhalation Solution:

The following regimens of Tyvaso DPI and Tyvaso give similar exposure:

<div class="scrollingtable"><table width="75%"> <col align="center" valign="top" width="50%"/> <col align="center" valign="top" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Tyvaso DPI<br/> Cartridge Strength</th><th align="center" class="Rrule">Tyvaso<br/> Number of Breaths</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">16 mcg</td><td align="center" class="Rrule">≤5 (≤30 mcg)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">32 mcg</td><td align="center" class="Rrule">6 to 7 (36 to 42 mcg)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">48 mcg</td><td align="center" class="Rrule">8 to 10 (48 to 60 mcg)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">64 mcg</td><td align="center" class="Rrule">11 to 13 (66 to 78 mcg)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">80 mcg</td><td align="center" class="Rrule">14 to 15 (84 to 90 mcg)</td> </tr> </tbody> </table></div>

Inhalation powder: Single-dose plastic cartridges containing 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg of treprostinil as a dry powder formulation.

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None.

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Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Tyvaso DPI may produce symptomatic hypotension.

Tyvaso DPI inhibits platelet aggregation and increases the risk of bleeding.

Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness [see Drug Interactions (7.3) and Clinical Pharmacology (12.3)].

Like other inhaled prostaglandins, Tyvaso DPI may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with Tyvaso DPI.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pulmonary Arterial Hypertension

Tyvaso DPI

In a 3-week, open-label, single-sequence, safety and tolerability study (BREEZE) conducted in 51 patients on stable doses of Tyvaso Inhalation Solution who switched to a corresponding dose of Tyvaso DPI, the most commonly reported adverse events on Tyvaso DPI during the 3-week treatment phase included cough, headache, dyspnea, and nausea. Patient tolerability, as assessed by incidence of new adverse events following transition to Tyvaso DPI, was consistent with the expected known safety profile of Tyvaso Inhalation Solution. Table 1 lists the adverse events that occurred at a rate of at least 4%.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1: Adverse Events in ≥4% of PAH Patients Receiving Tyvaso DPI in BREEZE (Treatment Phase)</span> </caption> <col align="center" valign="middle" width="50%"/> <col align="center" valign="middle" width="50%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" rowspan="2">Adverse Event</th><th align="center" class="Botrule Rrule">Tyvaso DPI (n=51)<br/> n (%)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Cough</td><td align="center" class="Rrule">18 (35.3)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">8 (15.7)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Dyspnea</td><td align="center" class="Rrule">4 (7.8)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">3 (5.9)</td> </tr> </tbody> </table></div>

The safety of Tyvaso DPI was also studied in an extension phase of the study in which 49 patients were dosed for a duration of 43 patient-years. Fifty-nine percent (59%) of patients achieved a dose of 64 mcg, 4 times daily or higher. The adverse events during this long-term, extension phase were similar to those observed in the 3-week treatment phase.

Tyvaso Inhalation Solution

In a 12-week, placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most commonly reported adverse reactions on Tyvaso Inhalation Solution included cough and throat irritation, headache, gastrointestinal effects, muscle, jaw or bone pain, dizziness, flushing, and syncope. Table 2 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with Tyvaso Inhalation Solution than with placebo.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 2: Adverse Events in ≥4% of PAH Patients Receiving Tyvaso Inhalation Solution and More Frequent<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> than Placebo in TRIUMPH I</span> </caption> <col align="center" valign="middle" width="50%"/> <col align="center" valign="middle" width="30%"/> <col align="center" valign="middle" width="20%"/> <thead> <tr class="First"> <th align="center" class="Lrule Rrule" rowspan="2">Adverse Event</th><th align="center" class="Botrule Rrule" colspan="2">Treatment<br/> n (%)</th> </tr> <tr class="Last"> <th align="center" class="Rrule">Tyvaso Inhalation Solution<br/> n=115</th><th align="center" class="Rrule">Placebo<br/> n=120</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>More than 3% greater than placebo</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Cough</td><td align="center" class="Rrule">62 (54)</td><td align="center" class="Rrule">35 (29)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">47 (41)</td><td align="center" class="Rrule">27 (23)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Throat Irritation / Pharyngolaryngeal Pain</td><td align="center" class="Rrule">29 (25)</td><td align="center" class="Rrule">17 (14)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">22 (19)</td><td align="center" class="Rrule">13 (11)</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Flushing</td><td align="center" class="Rrule">17 (15)</td><td align="center" class="Rrule">1 (&lt;1)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Syncope</td><td align="center" class="Rrule">7 (6)</td><td align="center" class="Rrule">1 (&lt;1)</td> </tr> </tbody> </table></div>

Pulmonary Hypertension Associated with ILD

In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions on Tyvaso Inhalation Solution were similar to the experience in studies of PAH.

In a human pharmacokinetic study conducted with bosentan (250 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and bosentan were observed.

In a human pharmacokinetic study conducted with sildenafil (60 mg/day) and an oral formulation of treprostinil (treprostinil diolamine), no pharmacokinetic interactions between treprostinil and sildenafil were observed.

In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A. Additionally, treprostinil does not induce cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A.

Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor, gemfibrozil, increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer, rifampin, decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8 [see Warnings and Precautions (5.3)].

Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively, in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S- warfarin and the international normalized ratio (INR) in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.

Risk Summary

Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, there are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations). In animal studies, no adverse reproductive and developmental effects were seen for treprostinil at ≥8 and ≥134 times the human exposure when based on Cmax and AUC, respectively, following a single, inhaled 64 mcg dose of treprostinil inhalation powder.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and embryo-fetal risk

Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality.

Data

Animal reproduction studies have been conducted with treprostinil via continuous subcutaneous administration and with treprostinil diolamine administered orally. In studies with orally administered treprostinil diolamine, no adverse effect doses for fetal viability/growth, fetal development (teratogenicity), and postnatal development were determined in rats. In pregnant rats, no evidence of harm to the fetus was observed following oral administration of treprostinil diolamine at the highest dose tested (20 mg/kg/day), which represents about 129 and 1366 times the human exposure, when based on Cmax and AUC, respectively, following a single, inhaled 64 mcg dose of treprostinil inhalation powder. In pregnant rabbits, external fetal and soft tissue malformations and fetal skeletal malformation occurred. The dose at which no adverse effects were seen (0.5 mg/kg/day) represents about 8 and 134 times the human exposure, when based on Cmax and AUC, respectively, following a single, inhaled 64 mcg dose of treprostinil inhalation powder. No treprostinil treatment-related effects on labor and delivery were seen in animal studies. Animal reproduction studies are not always predictive of human response.

Risk Summary

There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.

Safety and effectiveness in pediatric patients have not been established. Clinical studies of inhaled treprostinil did not include patients younger than 18 years to determine whether they respond differently from older patients.

Across clinical studies used to establish the effectiveness of Tyvaso Inhalation Solution in patients with PAH and PH-ILD, 268 (47.8%) patients aged 65 years and over were enrolled. The treatment effects and safety profile observed in geriatric patients were similar to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects with mild-to-moderate hepatic insufficiency. Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Clinical Pharmacology (12.3)].

No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis [see Clinical Pharmacology (12.3)].

In general, symptoms of overdose with inhaled treprostinil include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved.

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Tyvaso DPI consists of single-dose plastic cartridges filled with a white powder containing 1% of treprostinil, a prostacyclin mimetic, which is intended for administration by oral inhalation using the Tyvaso DPI Inhaler only. Treprostinil is adsorbed onto carrier particles consisting of fumaryl diketopiperazine (FDKP). Each cartridge contains 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg of treprostinil with approximate fill weights of 1.6 mg, 3.2 mg, 4.8 mg, 6.4 mg, or 8.0 mg of Tyvaso DPI, respectively.

Treprostinil is (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C23H34O5.

The structural formula of treprostinil is:

Treprostinil is a prostacyclin analogue. The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.

In a clinical trial of 240 healthy volunteers, single doses of Tyvaso Inhalation Solution 54 mcg (the target maintenance dose per session) and 84 mcg (supratherapeutic inhalation dose) prolonged the corrected QTc interval by approximately 10 ms. The QTc effect dissipated as the concentration of treprostinil decreased.

Absorption

Treprostinil plasma exposure data were obtained from a 6-treatment, 6-period, 6-sequence, crossover study of Tyvaso DPI and Tyvaso Inhalation Solution in healthy volunteers. The mean Cmax for the 16, 48, and 64 mcg doses of Tyvaso DPI were 0.39, 1.11, and 1.33 ng/mL, respectively, with corresponding median Tmax of 0.17 hr. The mean AUC0-5hr for the 16, 48, and 64 mcg doses of Tyvaso DPI were 0.275, 0.774, and 0.964 hr∙ng/mL, respectively.

Treprostinil systemic exposure (AUC0-5hr and Cmax) of Tyvaso DPI post-inhalation was approximately proportional to the doses administered (16 to 64 mcg).

Distribution

Following parenteral infusion, the steady state volume of distribution (Vss) of treprostinil is approximately 14 L/70 kg ideal body weight.

In vitro treprostinil is 91% bound to human plasma proteins over the 330 to 10,000 mcg/L concentration range.

Elimination

With a single dose of Tyvaso DPI, the mean terminal half-life of treprostinil ranged from 27 to 50 minutes.

Metabolism: Treprostinil is substantially metabolized by the liver, primarily by CYP2C8. Metabolites are excreted in urine (79%) and feces (13%) over 10 days. Five apparently inactive metabolites were detected in the urine, each accounting for 10 to 15% of the dose administered. Four of the metabolites are products of oxidation of the 3-hydroxyloctyl side chain and one is a glucuroconjugated derivative (treprostinil glucuronide).

Excretion: Of subcutaneously administered treprostinil, only 4% is excreted unchanged in urine.

Specific Populations

Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects presenting with mild-to-moderate hepatic insufficiency. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Use in Specific Populations (8.6)].

Renal Impairment

In patients with severe renal impairment requiring dialysis (n=8), administration of a single 1 mg dose of orally administered treprostinil pre- and post-dialysis resulted in AUC0-inf that was not significantly altered compared to healthy subjects [see Use in Specific Populations (8.7)].

A 2-year rat carcinogenicity study was performed with treprostinil inhalation at target doses of 5.26, 10.6, and 34.1 mcg/kg/day. There was no evidence for carcinogenic potential associated with treprostinil inhalation in rats at systemic exposure levels up to 36 times the clinical exposure at the 64 mcg dose of treprostinil inhalation powder. In vitro and in vivo genetic toxicology studies did not demonstrate any mutagenic or clastogenic effects of treprostinil. Treprostinil sodium did not affect fertility or mating performance of male or female rats given continuous subcutaneous infusions at rates of up to 450 ng treprostinil/kg/min. In this study, males were dosed from 10 weeks prior to mating and through the 2-week mating period. Females were dosed from 2 weeks prior to mating until gestational day 6.

Oral administration of treprostinil diolamine to Tg.rasH2 mice at 0, 5, 10, and 20 mg/kg/day in males and 0, 3, 7.5, and 15 mg/kg/day in females daily for 26 weeks did not significantly increase the incidence of tumors.

Treprostinil diolamine was tested in vivo in a rat micronucleus assay and did not induce an increased incidence of micronucleated polychromatic erythrocytes.

In a 2-year rat study with treprostinil inhalation solution at target doses of 5.26, 10.6, and 34.1 mcg/kg/day, there were more deaths (11) in the mid- and high-dose treprostinil groups during the first 9 weeks of the study, compared to 1 in control groups. At the high-dose level, males showed a higher incidence of inflammation in teeth and preputial gland, and females showed higher incidences of inflammation and urothelial hyperplasia in the urinary bladder. The exposures in rats at mid- and high-dose levels were about 14 and 36 times, respectively, the clinical exposure at the 64 mcg dose of treprostinil inhalation powder.

TRIUMPH I, was a 12-week, randomized, double-blind, placebo-controlled, multicenter study of patients with PAH (NCT00147199). The study population included 235 clinically stable subjects with PAH (WHO Group 1), nearly all with NYHA Class III (98%) symptoms who were receiving either bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase-5 inhibitor) for at least 3 months prior to study initiation. Concomitant therapy also could have included anticoagulants, other vasodilators (e.g., calcium channel blockers), diuretics, oxygen, and digitalis, but not a prostacyclin. These patients were administered either placebo or Tyvaso Inhalation Solution in 4 daily treatment sessions with a target dose of 9 breaths (54 mcg) per session over the course of the 12-week study. Patients were predominately female (82%), had the origin of PAH as idiopathic/heritable (56%), secondary to connective tissue diseases (33%) or secondary to HIV or previous use of anorexigens (12%); bosentan was the concomitant oral medication in 70% of those enrolled, sildenafil in 30%.

The primary efficacy endpoint of the trial was the change in 6MWD relative to baseline at 12 weeks. 6MWD was measured at peak exposure (between 10 and 60 minutes after dosing), and 3 to 5 hours after bosentan or 0.5 to 2 hours after sildenafil. Patients receiving Tyvaso Inhalation Solution had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12 (p<0.001). The distribution of these 6MWD changes from baseline at Week 12 were plotted across the range of observed values (Figure 1). 6MWD measured at trough exposure (defined as measurement of 6MWD at least 4 hours after dosing) improved by 14 meters. There were no placebo-controlled 6MWD assessments made after 12 weeks.

Figure 1: Distributions of 6MWD Changes from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso Inhalation Solution

The placebo-corrected median treatment effect on 6MWD was estimated (using the Hodges-Lehmann estimator) within various subpopulations defined by age quartile, gender, geographic region of the study site, disease etiology, baseline 6MWD quartile, and type of background therapy (Figure 2).

Figure 2: Placebo-Corrected Median Treatment Effect (Hodges-Lehmann Estimate with 95% CI) on 6MWD Change from Baseline at Week 12 During Peak Plasma Concentration of Tyvaso Inhalation Solution for Various Subgroups

In long-term follow-up of patients who were treated with Tyvaso Inhalation Solution in the pivotal study and the open-label extension (N=206) (NCT00147199), Kaplan-Meier estimates of survival at 1, 2, and 3 years were 97%, 91%, and 82%, respectively. These uncontrolled observations do not allow comparison with a control group not given Tyvaso Inhalation Solution and cannot be used to determine the long-term effect of Tyvaso Inhalation Solution on mortality.

INCREASE was a 16-week, randomized, double-blind, placebo-controlled, multicenter study that enrolled 326 patients with PH-ILD (NCT02630316). Enrolled study patients predominately had etiologies of idiopathic interstitial pneumonia (45%) inclusive of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema (25%), and WHO Group 3 connective tissue disease (22%). The mean baseline 6MWD was 260 meters.

Patients in the INCREASE study were randomized (1:1) to either placebo or Tyvaso Inhalation Solution in 4 daily treatment sessions with a target dose of 9 breaths (54 mcg) per session and a maximum dose of 12 breaths (72 mcg) per session over the course of the 16-week study. Approximately 75% of patients randomized to Tyvaso Inhalation Solution titrated up to a dose of 9 breaths, 4 times daily or greater, with 48% of patients randomized to Tyvaso Inhalation Solution reaching a dose of 12 breaths, 4 times daily during the study.

The primary efficacy endpoint was the change in 6MWD measured at peak exposure (between 10 and 60 minutes after dosing) from baseline to Week 16. Patients receiving Tyvaso Inhalation Solution had a placebo-corrected median change from baseline in peak 6MWD of 21 meters at Week 16 (p=0.004) using Hodges-Lehmann estimate (Figure 3).

Figure 3: Hodges-Lehmann Estimate of Treatment Effect by Visit for 6MWD at Peak Exposure of Tyvaso Inhalation Solution (PH-ILD)

The treatment effect on 6MWD at Week 16 was consistent for various subgroups, including etiology of PH-ILD, disease severity, age, sex, baseline hemodynamics, and dose (Figure 4).

Figure 4: Forest Plot on Subgroup Analyses of Peak 6MWD (Meter) at Week 16 (PH-ILD)

Time to clinical worsening in the INCREASE study was defined as the time of randomization until 1 of the following criteria were met: hospitalization due to a cardiopulmonary indication, decrease in 6MWD >15% from baseline directly related to PH-ILD at 2 consecutive visits and at least 24 hours apart, death (all causes), or lung transplantation. Treatment with Tyvaso Inhalation Solution in patients with PH-ILD resulted in numerically fewer hospitalizations. The numbers of reported deaths were the same for both treatment groups (Table 3). Overall, treatment with Tyvaso Inhalation Solution demonstrated a statistically significant increase in the time to first clinical worsening event (log-rank test p=0.041; Figure 5), and a 39% overall reduction in the risk of a clinical worsening event (HR=0.61 [95% CI; 0.40, 0.92]; Figure 5).

<div class="scrollingtable"><table width="85%"> <caption> <span>Table 3: Clinical Worsening Events (PH-ILD)</span> </caption> <col align="left" valign="top" width="5%"/> <col align="left" valign="top" width="40%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="12%"/> <col align="center" valign="top" width="18%"/> <thead> <tr class="First Last"> <th align="left" class="Lrule Rrule" colspan="2"></th><th align="center" class="Rrule">Tyvaso Inhalation Solution<br/> n=163<br/> n (%)</th><th align="center" class="Rrule">Placebo<br/> n=163<br/> n (%)</th><th align="center" class="Rrule">HR (95% CI)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Clinical worsening</span></td><td align="center" class="Rrule">37 (22.7%)</td><td align="center" class="Rrule">54 (33.1%)</td><td align="center" class="Rrule">0.61 (0.40, 0.92)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="4"><span class="Bold">First contributing event</span></td><td align="left" class="Rrule"><span class="Bold">Hospitalization due to a cardiopulmonary indication</span></td><td align="center" class="Rrule">18 (11.0%)</td><td align="center" class="Rrule">24 (14.7%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Decrease in 6MWD &gt;15% from baseline directly related to PH-ILD</span></td><td align="center" class="Rrule">13 (8.0%)</td><td align="center" class="Rrule">26 (16.0%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Death (all causes)</span></td><td align="center" class="Rrule">4 (2.5%)</td><td align="center" class="Rrule">4 (2.5%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Lung transplantation</span></td><td align="center" class="Rrule">2 (1.2%)</td><td align="center" class="Rrule">0</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="4"><span class="Bold">First of each event</span></td><td align="left" class="Rrule"><span class="Bold">Hospitalization due to a cardiopulmonary indication</span></td><td align="center" class="Rrule">21 (12.9%)</td><td align="center" class="Rrule">30 (18.4%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Decrease in 6MWD &gt;15% from baseline directly related to PH-ILD</span></td><td align="center" class="Rrule">16 (9.8%)</td><td align="center" class="Rrule">31 (19.0%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Rrule"><span class="Bold">Death (all causes)</span></td><td align="center" class="Rrule">8 (4.9%)</td><td align="center" class="Rrule">10 (6.1%)</td><td align="center" class="Rrule"></td> </tr> <tr class="Last"> <td align="left" class="Rrule"><span class="Bold">Lung transplantation</span></td><td align="center" class="Rrule">2 (1.2%)</td><td align="center" class="Rrule">1 (0.6%)</td><td align="center" class="Rrule"></td> </tr> </tbody> </table></div>

Figure 5: Kaplan-Meier Plot of Time to Clinical Worsening Events (PH-ILD)

Blister Storage:

<div class="scrollingtable"><table width="75%"> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="30%"/> <col align="left" valign="top" width="50%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule">Storage</th><th align="left" class="Rrule"></th><th align="left" class="Rrule"></th> </tr> <tr class="Last"> <th align="left" class="Lrule Rrule">Tyvaso DPI Presentation</th><th align="left" class="Rrule">Refrigerated storage 2°C to 8°C (36°F to 46°F)</th><th align="left" class="Rrule">Room temperature storage 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule">Sealed (Unopened) Blister Cards or Strips</td><td align="left" class="Rrule">May be stored until the expiration date printed on the blisters.</td><td align="left" class="Rrule">Must be used within 8 weeks.</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Opened Blister Strips</td><td align="left" class="Rrule">Do not put a blister card or strip back into the refrigerator after being opened or stored at room temperature.</td><td align="left" class="Rrule">Must be used within 3 days.</td> </tr> </tbody> </table></div>

Inhaler Storage:

Store at 2°C to 25°C (36°F to 77°F); excursions permitted. The Tyvaso DPI Inhaler may be stored refrigerated but should be at room temperature for 10 minutes before use. The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, the inhaler must be discarded and replaced with a new inhaler.

Handling:

If refrigerated, cartridges and inhaler should be at room temperature for 10 minutes before use.

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Instructions for Use)." }

Train patients in the administration process for Tyvaso DPI, including dosing, Tyvaso DPI Inhaler setup, operation, cleaning, and maintenance, according to the instructions for use [see Dosage and Administration (2.1, 2.2)].

{ "type": "p", "children": [], "text": "Train patients in the administration process for Tyvaso DPI, including dosing, Tyvaso DPI Inhaler setup, operation, cleaning, and maintenance, according to the instructions for use [see Dosage and Administration (2.1, 2.2)]." }

Advise patients that after 7 days of use, the inhaler must be discarded and replaced with a new inhaler [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "Advise patients that after 7 days of use, the inhaler must be discarded and replaced with a new inhaler [see Dosage and Administration (2.1)]." }

Instruct patients to use Tyvaso DPI only with the Tyvaso DPI Inhaler [see Dosage and Administration (2.1)].

{ "type": "p", "children": [], "text": "Instruct patients to use Tyvaso DPI only with the Tyvaso DPI Inhaler [see Dosage and Administration (2.1)]." }

If a scheduled treatment session is missed, resume therapy as soon as possible [see Dosage and Administration (2.2)].

{ "type": "p", "children": [], "text": "If a scheduled treatment session is missed, resume therapy as soon as possible [see Dosage and Administration (2.2)]." }

©Copyright 2024 United Therapeutics Corp. All rights reserved. Tyvaso DPI® and Tyvaso® are registered trademarks of United Therapeutics Corporation.

{ "type": "p", "children": [], "text": "\n©Copyright 2024 United Therapeutics Corp. All rights reserved. Tyvaso DPI® and Tyvaso® are registered trademarks of United Therapeutics Corporation." }

Tyvaso DPI manufactured by:

{ "type": "p", "children": [], "text": "Tyvaso DPI manufactured by:" }

MannKind Corporation Danbury, CT 06810

{ "type": "p", "children": [], "text": "MannKind Corporation Danbury, CT 06810" }

Tyvaso DPI manufactured for and distributed by:

{ "type": "p", "children": [], "text": "Tyvaso DPI manufactured for and distributed by:" }

United Therapeutics Corp. Research Triangle Park, NC 27709

{ "type": "p", "children": [], "text": "United Therapeutics Corp. Research Triangle Park, NC 27709" }

Instructions for Use

{ "type": "p", "children": [], "text": "\nInstructions for Use\n" }

TYVASO [ tī-vā'-sō ] DPI® (treprostinil) Inhalation Powder For oral inhalation only

{ "type": "p", "children": [], "text": "TYVASO [ tī-vā'-sō ] DPI®\n (treprostinil) Inhalation Powder For oral inhalation only" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="70%"/> <col align="left" valign="top" width="30%"/> <tbody class="Headless"> <tr> <td align="left" colspan="2">Table of Contents</td> </tr> <tr> <td align="left"></td><td align="left">page(s)</td> </tr> <tr> <td align="left"><span class="Bold">Read Before Starting</span></td><td align="left"><span class="Bold">1</span></td> </tr> <tr> <td align="left"><span class="Bold">Important Information</span></td><td align="left"><span class="Bold">2</span></td> </tr> <tr> <td align="left"><span class="Bold">Storing TYVASO DPI Inhalers and Cartridges</span></td><td align="left"><span class="Bold">3</span></td> </tr> <tr> <td align="left"><span class="Bold">Preparing to Inhale TYVASO DPI</span></td><td align="left"><span class="Bold">4-7</span></td> </tr> <tr> <td align="left"><span class="Bold">Inhaling TYVASO DPI</span></td><td align="left"><span class="Bold">8-9</span></td> </tr> <tr> <td align="left"><span class="Bold">Removing the Used Cartridge</span></td><td align="left"><span class="Bold">10</span></td> </tr> <tr> <td align="left"><span class="Bold">Disposing of TYVASO DPI Cartridge</span></td><td align="left"><span class="Bold">11</span></td> </tr> <tr> <td align="left"><span class="Bold">Inhaling Multiple Cartridges of TYVASO DPI</span></td><td align="left"><span class="Bold">12</span></td> </tr> <tr> <td align="left"><span class="Bold">Caring for Your TYVASO DPI Inhaler</span></td><td align="left"><span class="Bold">13</span></td> </tr> <tr> <td align="left"><span class="Bold">Disposing of Your TYVASO DPI Inhaler</span></td><td align="left"><span class="Bold">13</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"70%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" colspan=\"2\">Table of Contents</td>\n</tr>\n<tr>\n<td align=\"left\"></td><td align=\"left\">page(s)</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Read Before Starting</span></td><td align=\"left\"><span class=\"Bold\">1</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Important Information</span></td><td align=\"left\"><span class=\"Bold\">2</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Storing TYVASO DPI Inhalers and Cartridges</span></td><td align=\"left\"><span class=\"Bold\">3</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Preparing to Inhale TYVASO DPI</span></td><td align=\"left\"><span class=\"Bold\">4-7</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Inhaling TYVASO DPI</span></td><td align=\"left\"><span class=\"Bold\">8-9</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Removing the Used Cartridge</span></td><td align=\"left\"><span class=\"Bold\">10</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Disposing of TYVASO DPI Cartridge</span></td><td align=\"left\"><span class=\"Bold\">11</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Inhaling Multiple Cartridges of TYVASO DPI</span></td><td align=\"left\"><span class=\"Bold\">12</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Caring for Your TYVASO DPI Inhaler</span></td><td align=\"left\"><span class=\"Bold\">13</span></td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">Disposing of Your TYVASO DPI Inhaler</span></td><td align=\"left\"><span class=\"Bold\">13</span></td>\n</tr>\n</tbody>\n</table></div>" }

Read Before Starting

{ "type": "p", "children": [], "text": "Read Before Starting" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr> <td align="left"></td><td align="left" valign="bottom"><span class="Bold">Parts of the TYVASO DPI Inhaler</span> <br/> (see <span class="Bold"><a href="#figa">Figure A</a></span>)</td><td align="left" valign="bottom"><span class="Bold">Your Starter Kit includes a Carrying Case</span> <br/> (see <span class="Bold"><a href="#figb">Figure B</a></span>)</td><td align="left" valign="bottom"><span class="Bold">TYVASO DPI Blister Cards</span> <br/> (see <span class="Bold"><a href="#figc">Figure C</a></span>)</td> </tr> <tr> <td align="left" class="Rrule" rowspan="2">This Instructions for Use contains information on how to inhale TYVASO DPI (treprostinil) Inhalation Powder. Read this Instructions for Use carefully before you start using your inhaler and each time you get a new inhaler. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.<br/> <span class="Bold">Your healthcare provider should show you how to use your inhaler the right way before you use it for the first time.</span></td><td align="center" class="Rrule Toprule" rowspan="2"><a name="figa"></a><img alt="Figure A" src="/dailymed/image.cfm?name=tyvasoDPI-07.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure A</span></td><td align="left" class="Rrule Toprule">The TYVASO DPI inhaler and blister strips can be stored in the carrying case when using outside of your home or traveling.</td><td align="center" class="Toprule" rowspan="2" valign="middle"><a name="figc"></a><img alt="Figure C" src="/dailymed/image.cfm?name=tyvasoDPI-09.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure C</span></td> </tr> <tr> <td align="center" class="Rrule"><a name="figb"></a><img alt="Figure B" src="/dailymed/image.cfm?name=tyvasoDPI-08.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure B</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"></td><td align=\"left\" valign=\"bottom\"><span class=\"Bold\">Parts of the TYVASO DPI Inhaler</span>\n<br/> (see <span class=\"Bold\"><a href=\"#figa\">Figure A</a></span>)</td><td align=\"left\" valign=\"bottom\"><span class=\"Bold\">Your Starter Kit includes a Carrying Case</span>\n<br/> (see <span class=\"Bold\"><a href=\"#figb\">Figure B</a></span>)</td><td align=\"left\" valign=\"bottom\"><span class=\"Bold\">TYVASO DPI Blister Cards</span>\n<br/> (see <span class=\"Bold\"><a href=\"#figc\">Figure C</a></span>)</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Rrule\" rowspan=\"2\">This Instructions for Use contains information on how to inhale TYVASO DPI (treprostinil) Inhalation Powder. Read this Instructions for Use carefully before you start using your inhaler and each time you get a new inhaler. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.<br/>\n<span class=\"Bold\">Your healthcare provider should show you how to use your inhaler the right way before you use it for the first time.</span></td><td align=\"center\" class=\"Rrule Toprule\" rowspan=\"2\"><a name=\"figa\"></a><img alt=\"Figure A\" src=\"/dailymed/image.cfm?name=tyvasoDPI-07.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure A</span></td><td align=\"left\" class=\"Rrule Toprule\">The TYVASO DPI inhaler and blister strips can be stored in the carrying case when using outside of your home or traveling.</td><td align=\"center\" class=\"Toprule\" rowspan=\"2\" valign=\"middle\"><a name=\"figc\"></a><img alt=\"Figure C\" src=\"/dailymed/image.cfm?name=tyvasoDPI-09.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure C</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><a name=\"figb\"></a><img alt=\"Figure B\" src=\"/dailymed/image.cfm?name=tyvasoDPI-08.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure B</span></td>\n</tr>\n</tbody>\n</table></div>" }

Important Information

{ "type": "p", "children": [], "text": "Important Information" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="50%"/> <tbody class="Headless"> <tr> <td align="left"><span class="Bold">Important information you need to know before inhaling TYVASO DPI Inhalation Powder using the TYVASO DPI Inhaler</span></td><td align="left" rowspan="4"> <ul class="Disc"> <li>Take TYVASO DPI exactly as prescribed by your healthcare provider.</li> <li>Take TYVASO DPI 4 times per day while you are awake, about 4 hours apart.</li> <li>If you miss a dose, take it as soon as possible at your usual dose.</li> <li>If your prescribed dose is higher than 80 mcg per treatment session, you will need to use more than 1 cartridge. If using more than 1 cartridge, the cartridges can be used in any order, regardless of cartridge strength.</li> <li>If you need to use more than 1 cartridge for your dose, remove the used cartridge from the inhaler before getting a new one. You can tell a cartridge has been used when the cartridge cup has moved from the front to the middle position in the cartridge base.</li> <li> <span class="Bold">Only TYVASO DPI cartridges should be used with the TYVASO DPI Inhaler.</span> </li> <li> <span class="Bold">Each cartridge is for 1 time (single use) only.</span> Use a new cartridge for each treatment session. After each treatment session, throw away the used cartridge right away.</li> <li> <span class="Bold">Do not</span> open the cartridges. The inhaler opens the cartridge automatically during use.</li> <li> <span class="Bold">Warning:</span> If any powder from the cartridge spills on your hands, throw away the cartridge right away into regular household trash and wash your hands.<br/> Then start with a new cartridge.</li> <li> <span class="Bold">Do not</span> breathe in the TYVASO DPI treprostinil powder in any other way.</li> <li> <span class="Bold">Do not</span> put cartridges in your mouth.</li> <li> <span class="Bold">Do not</span> swallow cartridges.</li> <li>Use only 1 inhaler at a time. The same inhaler should be used even when needing to use more than 1 cartridge for your dose. Inhale 1 cartridge at a time.</li> <li>The inhaler lasts for 7 days. After 7 days of use, throw away your used inhaler and get a new one.</li> <li>Store the inhaler in a clean, dry place with the mouthpiece cover on until your next dose.</li> </ul> </td> </tr> <tr> <td align="left"><span class="Bold">TYVASO DPI cartridges come in 5 strengths</span> (see <span class="Bold"><a href="#figd">Figure D</a></span>).<br/> <span class="Bold">Important:</span> Always make sure you have the right number of TYVASO DPI cartridges for your dose before you start. Only use TYVASO DPI cartridges with the TYVASO DPI Inhaler.</td> </tr> <tr> <td align="center"><a name="figd"></a><img alt="Figure D" src="/dailymed/image.cfm?name=tyvasoDPI-10.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure D</span></td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="middle"><span class="Bold">If you are having problems with your TYVASO DPI Inhaler, have any side effects, or if your TYVASO DPI Inhaler breaks and you need a new one, please call 1-844-UNITHER (1-844-864-8437).</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\"><span class=\"Bold\">Important information you need to know before inhaling TYVASO DPI Inhalation Powder using the TYVASO DPI Inhaler</span></td><td align=\"left\" rowspan=\"4\">\n<ul class=\"Disc\">\n<li>Take TYVASO DPI exactly as prescribed by your healthcare provider.</li>\n<li>Take TYVASO DPI 4 times per day while you are awake, about 4 hours apart.</li>\n<li>If you miss a dose, take it as soon as possible at your usual dose.</li>\n<li>If your prescribed dose is higher than 80 mcg per treatment session, you will need to use more than 1 cartridge. If using more than 1 cartridge, the cartridges can be used in any order, regardless of cartridge strength.</li>\n<li>If you need to use more than 1 cartridge for your dose, remove the used cartridge from the inhaler before getting a new one. You can tell a cartridge has been used when the cartridge cup has moved from the front to the middle position in the cartridge base.</li>\n<li>\n<span class=\"Bold\">Only TYVASO DPI cartridges should be used with the TYVASO DPI Inhaler.</span>\n</li>\n<li>\n<span class=\"Bold\">Each cartridge is for 1 time (single use) only.</span> Use a new cartridge for each treatment session. After each treatment session, throw away the used cartridge right away.</li>\n<li>\n<span class=\"Bold\">Do not</span> open the cartridges. The inhaler opens the cartridge automatically during use.</li>\n<li>\n<span class=\"Bold\">Warning:</span> If any powder from the cartridge spills on your hands, throw away the cartridge right away into regular household trash and wash your hands.<br/> Then start with a new cartridge.</li>\n<li>\n<span class=\"Bold\">Do not</span> breathe in the TYVASO DPI treprostinil powder in any other way.</li>\n<li>\n<span class=\"Bold\">Do not</span> put cartridges in your mouth.</li>\n<li>\n<span class=\"Bold\">Do not</span> swallow cartridges.</li>\n<li>Use only 1 inhaler at a time. The same inhaler should be used even when needing to use more than 1 cartridge for your dose. Inhale 1 cartridge at a time.</li>\n<li>The inhaler lasts for 7 days. After 7 days of use, throw away your used inhaler and get a new one.</li>\n<li>Store the inhaler in a clean, dry place with the mouthpiece cover on until your next dose.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\"><span class=\"Bold\">TYVASO DPI cartridges come in 5 strengths</span> (see <span class=\"Bold\"><a href=\"#figd\">Figure D</a></span>).<br/>\n<span class=\"Bold\">Important:</span> Always make sure you have the right number of TYVASO DPI cartridges for your dose before you start. Only use TYVASO DPI cartridges with the TYVASO DPI Inhaler.</td>\n</tr>\n<tr>\n<td align=\"center\"><a name=\"figd\"></a><img alt=\"Figure D\" src=\"/dailymed/image.cfm?name=tyvasoDPI-10.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure D</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\" valign=\"middle\"><span class=\"Bold\">If you are having problems with your TYVASO DPI Inhaler, have any side effects, or if your TYVASO DPI Inhaler breaks and you need a new one, please call 1-844-UNITHER (1-844-864-8437).</span></td>\n</tr>\n</tbody>\n</table></div>" }

Storing TYVASO DPI Inhalers and Cartridges

{ "type": "p", "children": [], "text": "Storing TYVASO DPI Inhalers and Cartridges" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="11%"/> <col align="left" valign="top" width="12%"/> <col align="center" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <thead> <tr> <th align="left" class="Lrule">Storing TYVASO DPI Inhalers</th><th align="left" class="Lrule" colspan="4">Storing Unopened Blister Cards and Strips</th><th align="left" class="Lrule">Storing Opened Blister Strips</th> </tr> </thead> <tbody> <tr> <td align="left" class="Lrule">Store TYVASO DPI Inhalers, with the mouthpiece on, in a clean, dry place at room temperature between 68°F to 77°F (20°C to 25°C), such as a drawer or medicine cabinet (see <span class="Bold"><a href="#fige">Figure E</a></span>).<br/> Inhalers may be stored in the refrigerator between 36°F to 46°F (2°C to 8°C), but should be left out at room temperature for 10 minutes before use.</td><td align="left" class="Lrule" colspan="3">Store unopened blister cards and strips in a clean, dry place at room temperature, such as a drawer or medicine cabinet. You can store in the carrying case when using outside your home or traveling (see <span class="Bold"><a href="#figf">Figure F</a></span>). <dl> <dt> </dt> <dd> <span class="Bold">Do not</span> use after 8 weeks if stored at room temperature.</dd> </dl>Unopened blister cards and strips may also be stored in the refrigerator (see <span class="Bold"><a href="#figg">Figure G</a></span>).</td><td align="center" valign="bottom"><a name="figf"></a><img alt="Figure F" src="/dailymed/image.cfm?name=tyvasoDPI-12.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure F</span></td><td align="left" class="Lrule">Store opened blister strips in a clean, dry place at room temperature (see <span class="Bold"><a href="#figh">Figure H</a></span>), such as a drawer or medicine cabinet.<br/> Opened blister strips must be used within 3 days. <dl> <dt> </dt> <dd> <span class="Bold">Do not</span> put a blister strip back into the refrigerator after being opened or stored at room temperature.</dd> </dl> </td> </tr> <tr> <td align="left" class="Lrule"> <dl> <dt> </dt> <dd> <span class="Bold">Do not</span> leave or store cartridges in the inhaler.<br/> <span class="Bold">Keep out of the reach of children.</span> </dd> </dl> </td><td align="left" class="Lrule" colspan="3"> <dl> <dt> </dt> <dd> <span class="Bold">Do not</span> use after the Expiration Date has passed.</dd> </dl> </td><td align="center"></td><td align="center" class="Lrule" rowspan="3"><a name="figh"></a><img alt="Figure H" src="/dailymed/image.cfm?name=tyvasoDPI-13.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><span class="Bold">Figure H</span></td> </tr> <tr> <td align="center" class="Lrule" rowspan="2"><a name="fige"></a><img alt="Figure E" src="/dailymed/image.cfm?name=tyvasoDPI-11.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure E</span></td><td align="left" class="Lrule"></td><td align="left" class="Lrule Rrule Toprule" colspan="2"><span class="Bold">Important:</span> If refrigerated, cartridges and inhaler should be left out at room temperature for 10 minutes before use.</td><td align="center" class="Rrule" rowspan="2"><a name="figg"></a><img alt="Figure G" src="/dailymed/image.cfm?name=tyvasoDPI-16.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><span class="Bold">Figure G</span></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="center" class="Botrule Lrule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-14.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">ROOM TEMPERATURE</span></td><td align="center" class="Botrule Rrule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-15.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">10 mins.</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"11%\"/>\n<col align=\"left\" valign=\"top\" width=\"12%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<thead>\n<tr>\n<th align=\"left\" class=\"Lrule\">Storing TYVASO DPI Inhalers</th><th align=\"left\" class=\"Lrule\" colspan=\"4\">Storing Unopened Blister Cards and Strips</th><th align=\"left\" class=\"Lrule\">Storing Opened Blister Strips</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Lrule\">Store TYVASO DPI Inhalers, with the mouthpiece on, in a clean, dry place at room temperature between 68°F to 77°F (20°C to 25°C), such as a drawer or medicine cabinet (see <span class=\"Bold\"><a href=\"#fige\">Figure E</a></span>).<br/> Inhalers may be stored in the refrigerator between 36°F to 46°F (2°C to 8°C), but should be left out at room temperature for 10 minutes before use.</td><td align=\"left\" class=\"Lrule\" colspan=\"3\">Store unopened blister cards and strips in a clean, dry place at room temperature, such as a drawer or medicine cabinet. You can store in the carrying case when using outside your home or traveling (see <span class=\"Bold\"><a href=\"#figf\">Figure F</a></span>). \t\t\t\t\t\t\t\t\t\t\t<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> use after 8 weeks if stored at room temperature.</dd>\n</dl>Unopened blister cards and strips may also be stored in the refrigerator (see <span class=\"Bold\"><a href=\"#figg\">Figure G</a></span>).</td><td align=\"center\" valign=\"bottom\"><a name=\"figf\"></a><img alt=\"Figure F\" src=\"/dailymed/image.cfm?name=tyvasoDPI-12.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure F</span></td><td align=\"left\" class=\"Lrule\">Store opened blister strips in a clean, dry place at room temperature (see <span class=\"Bold\"><a href=\"#figh\">Figure H</a></span>), such as a drawer or medicine cabinet.<br/> Opened blister strips must be used within 3 days. \t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> put a blister strip back into the refrigerator after being opened or stored at room temperature.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\">\n<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> leave or store cartridges in the inhaler.<br/>\n<span class=\"Bold\">Keep out of the reach of children.</span>\n</dd>\n</dl>\n</td><td align=\"left\" class=\"Lrule\" colspan=\"3\">\n<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> use after the Expiration Date has passed.</dd>\n</dl>\n</td><td align=\"center\"></td><td align=\"center\" class=\"Lrule\" rowspan=\"3\"><a name=\"figh\"></a><img alt=\"Figure H\" src=\"/dailymed/image.cfm?name=tyvasoDPI-13.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><span class=\"Bold\">Figure H</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\" rowspan=\"2\"><a name=\"fige\"></a><img alt=\"Figure E\" src=\"/dailymed/image.cfm?name=tyvasoDPI-11.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure E</span></td><td align=\"left\" class=\"Lrule\"></td><td align=\"left\" class=\"Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Important:</span> If refrigerated, cartridges and inhaler should be left out at room temperature for 10 minutes before use.</td><td align=\"center\" class=\"Rrule\" rowspan=\"2\"><a name=\"figg\"></a><img alt=\"Figure G\" src=\"/dailymed/image.cfm?name=tyvasoDPI-16.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><span class=\"Bold\">Figure G</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"center\" class=\"Botrule Lrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-14.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">ROOM TEMPERATURE</span></td><td align=\"center\" class=\"Botrule Rrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-15.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">10 mins.</span></td>\n</tr>\n</tbody>\n</table></div>" }

Preparing to Inhale TYVASO DPI

{ "type": "p", "children": [], "text": "Preparing to Inhale TYVASO DPI" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="center" valign="top" width="9%"/> <col align="center" valign="top" width="9%"/> <col align="center" valign="top" width="9%"/> <col align="center" valign="top" width="9%"/> <col align="center" valign="top" width="9%"/> <col align="left" valign="top" width="14%"/> <col align="left" valign="top" width="14%"/> <col align="left" valign="top" width="27%"/> <tbody class="Headless"> <tr> <td align="left" class="Rrule" colspan="5"><span class="Bold">Step 1 : Select the TYVASO DPI cartridges for your dose</span> (see <span class="Bold"><a href="#figi">Figure I</a></span>)</td><td align="left" class="Rrule" colspan="2"><span class="Bold">Step 2 : Tear off 1 strip</span></td><td align="left"><span class="Bold">Step 3 : Check the expiration date on the strip</span></td> </tr> <tr> <td align="left" class="Rrule" colspan="5">Select the TYVASO DPI cartridges for your dose (see <span class="Bold"><a href="#figi">Figure I</a></span>).<br/> <dl> <dt> </dt> <dd> <span class="Bold">Note:</span> If using more than 1 cartridge, the cartridges can be used in any order, regardless of cartridge strength.</dd> </dl> </td><td align="left" rowspan="4">Tear along the perforation to remove 1 strip from the blister card (see <span class="Bold"><a href="#figj">Figure J</a></span>).</td><td align="center" class="Rrule" rowspan="4"><a name="figj"></a><img alt="Figure J" src="/dailymed/image.cfm?name=tyvasoDPI-21.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure J</span></td><td align="left">Check the expiration date on the foil strip label (see <span class="Bold"><a href="#figk">Figure K</a></span>). <dl> <dt> </dt> <dd> <span class="Bold">Do not</span> use the cartridges if the Expiration Date on the strip has passed.</dd> </dl> </td> </tr> <tr> <td align="center" class="Botrule Rrule">If your prescribed TYVASO DPI dose is 16 mcg, use...<br/> <img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-17.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="center" class="Botrule Rrule">If your prescribed TYVASO DPI dose is 32 mcg, use...<br/> <img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-18.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="center" class="Botrule Rrule">If your prescribed TYVASO DPI dose is 48 mcg, use...<br/> <img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-19.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="center" class="Botrule Rrule">If your prescribed TYVASO DPI dose is 64 mcg, use...<br/> <img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-20.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="center" class="Botrule Rrule">If your prescribed TYVASO DPI dose is 80 mcg, use...<br/> <img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-20a.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="center" rowspan="3"><a name="figk"></a><img alt="Figure K" src="/dailymed/image.cfm?name=tyvasoDPI-22.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure K</span></td> </tr> <tr> <td align="left" class="Rrule" colspan="5"><span class="Bold">If your prescribed TYVASO DPI dose is more than 80 mcg per treatment session, you will need to use more than 1 cartridge to get the right dose.<br/> Example:</span> If your prescribed TYVASO DPI dose is 96 mcg per treatment session, you can use...</td> </tr> <tr> <td align="center" class="Rrule" colspan="5"><a name="figi"></a><img alt="Figure I" src="/dailymed/image.cfm?name=tyvasoDPI-23.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure I</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"center\" valign=\"top\" width=\"9%\"/>\n<col align=\"center\" valign=\"top\" width=\"9%\"/>\n<col align=\"center\" valign=\"top\" width=\"9%\"/>\n<col align=\"center\" valign=\"top\" width=\"9%\"/>\n<col align=\"center\" valign=\"top\" width=\"9%\"/>\n<col align=\"left\" valign=\"top\" width=\"14%\"/>\n<col align=\"left\" valign=\"top\" width=\"14%\"/>\n<col align=\"left\" valign=\"top\" width=\"27%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" class=\"Rrule\" colspan=\"5\"><span class=\"Bold\">Step 1 : Select the TYVASO DPI cartridges for your dose</span> (see <span class=\"Bold\"><a href=\"#figi\">Figure I</a></span>)</td><td align=\"left\" class=\"Rrule\" colspan=\"2\"><span class=\"Bold\">Step 2 : Tear off 1 strip</span></td><td align=\"left\"><span class=\"Bold\">Step 3 : Check the expiration date on the strip</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Rrule\" colspan=\"5\">Select the TYVASO DPI cartridges for your dose (see <span class=\"Bold\"><a href=\"#figi\">Figure I</a></span>).<br/>\n<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> If using more than 1 cartridge, the cartridges can be used in any order, regardless of cartridge strength.</dd>\n</dl>\n</td><td align=\"left\" rowspan=\"4\">Tear along the perforation to remove 1 strip from the blister card (see <span class=\"Bold\"><a href=\"#figj\">Figure J</a></span>).</td><td align=\"center\" class=\"Rrule\" rowspan=\"4\"><a name=\"figj\"></a><img alt=\"Figure J\" src=\"/dailymed/image.cfm?name=tyvasoDPI-21.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure J</span></td><td align=\"left\">Check the expiration date on the foil strip label (see <span class=\"Bold\"><a href=\"#figk\">Figure K</a></span>). \t\t\t\t\t\t\t\t\t\t<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Do not</span> use the cartridges if the Expiration Date on the strip has passed.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Rrule\">If your prescribed TYVASO DPI dose is 16 mcg, use...<br/>\n<img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-17.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"center\" class=\"Botrule Rrule\">If your prescribed TYVASO DPI dose is 32 mcg, use...<br/>\n<img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-18.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"center\" class=\"Botrule Rrule\">If your prescribed TYVASO DPI dose is 48 mcg, use...<br/>\n<img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-19.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"center\" class=\"Botrule Rrule\">If your prescribed TYVASO DPI dose is 64 mcg, use...<br/>\n<img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-20.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"center\" class=\"Botrule Rrule\">If your prescribed TYVASO DPI dose is 80 mcg, use...<br/>\n<img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-20a.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"center\" rowspan=\"3\"><a name=\"figk\"></a><img alt=\"Figure K\" src=\"/dailymed/image.cfm?name=tyvasoDPI-22.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure K</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Rrule\" colspan=\"5\"><span class=\"Bold\">If your prescribed TYVASO DPI dose is more than 80 mcg per treatment session, you will need to use more than 1 cartridge to get the right dose.<br/> Example:</span> If your prescribed TYVASO DPI dose is 96 mcg per treatment session, you can use...</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\" colspan=\"5\"><a name=\"figi\"></a><img alt=\"Figure I\" src=\"/dailymed/image.cfm?name=tyvasoDPI-23.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure I</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="2%"/> <col align="left" valign="top" width="18%"/> <col align="center" valign="top" width="15%"/> <col align="center" valign="top" width="13%"/> <col align="center" valign="top" width="2%"/> <col align="left" valign="top" width="10%"/> <col align="left" valign="middle" width="40%"/> <thead> <tr> <th align="left" class="Lrule" colspan="5">Step 4 : Remove cartridge(s) from strip</th><th align="left" class="Lrule" colspan="2">Step 5 : Check supplies before continuing</th> </tr> </thead> <tbody> <tr> <td align="left" class="Lrule" colspan="5" rowspan="2"> <ul class="Disc"> <li>Remove cartridge(s) from the strip by pushing on the white plastic to push the cartridge out (see <span class="Bold"><a href="#figl">Figure L</a></span>).<br/>   <span class="Bold">Note:</span> Pushing on the cup will not damage the cartridge.</li> <li>Make sure to remove the right number of cartridges for your dose.</li> <li>After you have removed a cartridge (or cartridges) from the strip, if any unused cartridges remain in the strip, store the strip at room temperature.<br/>   <span class="Bold">Do not</span> put a blister strip back into the refrigerator after being opened.</li> </ul> </td><td align="left" class="Lrule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-25.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="left">Check that you have the right cartridge(s) for your dose.</td> </tr> <tr> <td align="left" class="Lrule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-26.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="left">Only use one inhaler for multiple cartridges. Your inhaler lasts for 7 days.</td> </tr> <tr> <td align="center" class="Lrule" colspan="3"> <p class="First"> <a name="figl"></a><img alt="Figure L" src="/dailymed/image.cfm?name=tyvasoDPI-24.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></p> <br/> <span class="Bold">Figure L</span></td><td align="center" colspan="2"></td><td align="left" class="Lrule"></td><td align="left"></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="left" class="Botrule Lrule Toprule"><span class="Bold">Important:</span> If refrigerated, cartridges and inhaler should be left out at room temperature for 10 minutes before use.</td><td align="center" class="Botrule Toprule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-27.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">ROOM TEMPERATURE</span></td><td align="center" class="Botrule Rrule Toprule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-28.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">10 mins.</span></td><td align="center" class="Rrule"></td><td align="left" class="Lrule"></td><td align="left"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"18%\"/>\n<col align=\"center\" valign=\"top\" width=\"15%\"/>\n<col align=\"center\" valign=\"top\" width=\"13%\"/>\n<col align=\"center\" valign=\"top\" width=\"2%\"/>\n<col align=\"left\" valign=\"top\" width=\"10%\"/>\n<col align=\"left\" valign=\"middle\" width=\"40%\"/>\n<thead>\n<tr>\n<th align=\"left\" class=\"Lrule\" colspan=\"5\">Step 4 : Remove cartridge(s) from strip</th><th align=\"left\" class=\"Lrule\" colspan=\"2\">Step 5 : Check supplies before continuing</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"5\" rowspan=\"2\">\n<ul class=\"Disc\">\n<li>Remove cartridge(s) from the strip by pushing on the white plastic to push the cartridge out (see <span class=\"Bold\"><a href=\"#figl\">Figure L</a></span>).<br/>   <span class=\"Bold\">Note:</span> Pushing on the cup will not damage the cartridge.</li>\n<li>Make sure to remove the right number of cartridges for your dose.</li>\n<li>After you have removed a cartridge (or cartridges) from the strip, if any unused cartridges remain in the strip, store the strip at room temperature.<br/>   <span class=\"Bold\">Do not</span> put a blister strip back into the refrigerator after being opened.</li>\n</ul>\n</td><td align=\"left\" class=\"Lrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-25.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"left\">Check that you have the right cartridge(s) for your dose.</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-26.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"left\">Only use one inhaler for multiple cartridges. Your inhaler lasts for 7 days.</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\" colspan=\"3\">\n<p class=\"First\">\n<a name=\"figl\"></a><img alt=\"Figure L\" src=\"/dailymed/image.cfm?name=tyvasoDPI-24.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></p>\n<br/>\n<span class=\"Bold\">Figure L</span></td><td align=\"center\" colspan=\"2\"></td><td align=\"left\" class=\"Lrule\"></td><td align=\"left\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"left\" class=\"Botrule Lrule Toprule\"><span class=\"Bold\">Important:</span> If refrigerated, cartridges and inhaler should be left out at room temperature for 10 minutes before use.</td><td align=\"center\" class=\"Botrule Toprule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-27.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">ROOM TEMPERATURE</span></td><td align=\"center\" class=\"Botrule Rrule Toprule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-28.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">10 mins.</span></td><td align=\"center\" class=\"Rrule\"></td><td align=\"left\" class=\"Lrule\"></td><td align=\"left\"></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <thead> <tr> <th align="left" colspan="4">Step 6: Load a cartridge</th> </tr> </thead> <tbody> <tr> <td align="left" class="Rrule"><span class="Bold">Place Inhaler on Flat Surface</span> <br/> Place the inhaler on a flat surface (see <span class="Bold"><a href="#figm">Figure M</a></span>).</td><td align="left" class="Rrule" rowspan="2"><span class="Bold">Open Inhaler</span> <br/> Open the inhaler by lifting the mouthpiece to an upright (vertical) position (see <span class="Bold"><a href="#fign">Figure N</a></span>).<br/> <span class="Bold">Important:</span> If the cartridge came from a strip stored in the refrigerator (or if you stored the inhaler in the refrigerator), leave the cartridge and inhaler at room temperature for 10 minutes to remove condensation.</td><td align="left" colspan="2" rowspan="2"><span class="Bold">Place Cartridge in Inhaler</span> <ul class="Disc"> <li>Hold the cartridge with the cup facing down (see <span class="Bold"><a href="#figo">Figure O</a></span>).</li> <li>Line up the cartridge with the opening in the inhaler.<br/> The pointed end of the cartridge should line up with the pointed end in the inhaler (see <span class="Bold"><a href="#figp">Figure P</a></span>).</li> <li>Place the cartridge into the inhaler so that it lies flat.</li> </ul> </td> </tr> <tr> <td align="center" class="Rrule"><a name="figm"></a><img alt="Figure M" src="/dailymed/image.cfm?name=tyvasoDPI-29.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure M</span></td> </tr> <tr> <td align="left" class="Rrule"></td><td align="center" class="Rrule" valign="bottom"><a name="fign"></a><img alt="Figure N" src="/dailymed/image.cfm?name=tyvasoDPI-30.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure N</span></td><td align="center"><a name="figo"></a><img alt="Figure O" src="/dailymed/image.cfm?name=tyvasoDPI-31.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure O</span></td><td align="center"><a name="figp"></a><img alt="Figure P" src="/dailymed/image.cfm?name=tyvasoDPI-32.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure P</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"4\">Step 6: Load a cartridge</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Rrule\"><span class=\"Bold\">Place Inhaler on Flat Surface</span>\n<br/> Place the inhaler on a flat surface (see <span class=\"Bold\"><a href=\"#figm\">Figure M</a></span>).</td><td align=\"left\" class=\"Rrule\" rowspan=\"2\"><span class=\"Bold\">Open Inhaler</span>\n<br/> Open the inhaler by lifting the mouthpiece to an upright (vertical) position (see <span class=\"Bold\"><a href=\"#fign\">Figure N</a></span>).<br/>\n<span class=\"Bold\">Important:</span> If the cartridge came from a strip stored in the refrigerator (or if you stored the inhaler in the refrigerator), leave the cartridge and inhaler at room temperature for 10 minutes to remove condensation.</td><td align=\"left\" colspan=\"2\" rowspan=\"2\"><span class=\"Bold\">Place Cartridge in Inhaler</span>\n<ul class=\"Disc\">\n<li>Hold the cartridge with the cup facing down (see <span class=\"Bold\"><a href=\"#figo\">Figure O</a></span>).</li>\n<li>Line up the cartridge with the opening in the inhaler.<br/> The pointed end of the cartridge should line up with the pointed end in the inhaler (see <span class=\"Bold\"><a href=\"#figp\">Figure P</a></span>).</li>\n<li>Place the cartridge into the inhaler so that it lies flat.</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\"><a name=\"figm\"></a><img alt=\"Figure M\" src=\"/dailymed/image.cfm?name=tyvasoDPI-29.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure M</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Rrule\"></td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><a name=\"fign\"></a><img alt=\"Figure N\" src=\"/dailymed/image.cfm?name=tyvasoDPI-30.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure N</span></td><td align=\"center\"><a name=\"figo\"></a><img alt=\"Figure O\" src=\"/dailymed/image.cfm?name=tyvasoDPI-31.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure O</span></td><td align=\"center\"><a name=\"figp\"></a><img alt=\"Figure P\" src=\"/dailymed/image.cfm?name=tyvasoDPI-32.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure P</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="17%"/> <col align="center" valign="top" width="16%"/> <col align="center" valign="top" width="17%"/> <tbody class="Headless"> <tr> <td align="left" class="Lrule" colspan="2" rowspan="2"><span class="Bold">Close Inhaler</span> <br/> Close the inhaler (this will open the cartridge). You should feel a snap when the inhaler is closed (see <span class="Bold"><a href="#figq">Figure Q</a></span>).<br/> <span class="Bold">Important:</span> Now that the cartridge is loaded, keep the inhaler level to avoid loss of the TYVASO DPI powder, until it is in your mouth (see <span class="Bold"><a href="#figr">Figure R</a></span>).</td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="3"><span class="Bold">Not keeping the inhaler level could cause a loss of TYVASO DPI powder (see <a href="#figs">Figure S</a>)</span></td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">If any powder from the cartridge spills:</span> <ul class="Disc"> <li>Wash your hands right away if the powder comes into contact with your hands,</li> <li>Throw away the cartridge into household trash, and</li> <li>Repeat Steps 4, 5, and 6 to load a new cartridge</li> </ul> </td> </tr> <tr> <td align="center" class="Lrule" rowspan="3" valign="bottom"><a name="figq"></a><img alt="Figure Q" src="/dailymed/image.cfm?name=tyvasoDPI-33.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure Q</span></td><td align="center" rowspan="3" valign="bottom"><a name="figr"></a><img alt="Figure R" src="/dailymed/image.cfm?name=tyvasoDPI-34.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure R</span></td><td align="center" class="Lrule"><a name="figs"></a><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-35.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> DO NOT turn inhaler upside down.</td><td align="center"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-36.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> DO NOT point the mouthpiece down.</td><td align="center" class="Rrule"><img alt="Image" src="/dailymed/image.cfm?name=tyvasoDPI-37.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> DO NOT shake or drop the inhaler.</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="3"><span class="Bold">This can cause a loss of TYVASO DPI powder.</span></td> </tr> <tr> <td align="center" colspan="3"><span class="Bold">Figure S</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"17%\"/>\n<col align=\"center\" valign=\"top\" width=\"16%\"/>\n<col align=\"center\" valign=\"top\" width=\"17%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\" rowspan=\"2\"><span class=\"Bold\">Close Inhaler</span>\n<br/> Close the inhaler (this will open the cartridge). You should feel a snap when the inhaler is closed (see <span class=\"Bold\"><a href=\"#figq\">Figure Q</a></span>).<br/>\n<span class=\"Bold\">Important:</span> Now that the cartridge is loaded, keep the inhaler level to avoid loss of the TYVASO DPI powder, until it is in your mouth (see <span class=\"Bold\"><a href=\"#figr\">Figure R</a></span>).</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\"><span class=\"Bold\">Not keeping the inhaler level could cause a loss of TYVASO DPI powder (see <a href=\"#figs\">Figure S</a>)</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">If any powder from the cartridge spills:</span>\n<ul class=\"Disc\">\n<li>Wash your hands right away if the powder comes into contact with your hands,</li>\n<li>Throw away the cartridge into household trash, and</li>\n<li>Repeat Steps 4, 5, and 6 to load a new cartridge</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\" rowspan=\"3\" valign=\"bottom\"><a name=\"figq\"></a><img alt=\"Figure Q\" src=\"/dailymed/image.cfm?name=tyvasoDPI-33.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure Q</span></td><td align=\"center\" rowspan=\"3\" valign=\"bottom\"><a name=\"figr\"></a><img alt=\"Figure R\" src=\"/dailymed/image.cfm?name=tyvasoDPI-34.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure R</span></td><td align=\"center\" class=\"Lrule\"><a name=\"figs\"></a><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-35.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/> DO NOT turn inhaler upside down.</td><td align=\"center\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-36.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/> DO NOT point the mouthpiece down.</td><td align=\"center\" class=\"Rrule\"><img alt=\"Image\" src=\"/dailymed/image.cfm?name=tyvasoDPI-37.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/> DO NOT shake or drop the inhaler.</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">This can cause a loss of TYVASO DPI powder.</span></td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"3\"><span class=\"Bold\">Figure S</span></td>\n</tr>\n</tbody>\n</table></div>" }

Inhaling TYVASO DPI

{ "type": "p", "children": [], "text": "Inhaling TYVASO DPI" }

Before inhaling TYVASO DPI, fully review all parts of Step 7 before you take your dose.

{ "type": "p", "children": [], "text": "\nBefore inhaling TYVASO DPI, fully review all parts of Step 7 before you take your dose.\n" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="50%"/> <thead> <tr> <th align="left">Step 7: Inhale Your Dose</th><th align="left" colspan="2"></th> </tr> </thead> <tbody> <tr> <td align="left" class="Rrule"><span class="Bold">Remove the Mouthpiece Cover</span> (see <span class="Bold"><a href="#figt">Figure T</a></span>).<br/> <span class="Bold">Important:</span> Keep the inhaler level during and after removal of the blue mouthpiece cover to prevent loss of TYVASO DPI powder.</td><td align="left" class="Rrule"><span class="Bold">Hold Inhaler Near Cheek</span> <br/> While keeping the inhaler level, carefully pick up the inhaler and bring it near your cheek, but not in front of your mouth (see <span class="Bold"><a href="#figu">Figure U</a></span>).</td><td align="left"><span class="Bold">Exhale</span> <br/> Holding the inhaler away from your mouth, fully blow out (exhale) (see <span class="Bold"><a href="#figv">Figure V</a></span>).</td> </tr> <tr> <td align="center" class="Rrule" valign="bottom"><a name="figt"></a><img alt="Figure T" src="/dailymed/image.cfm?name=tyvasoDPI-38.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure T</span></td><td align="center" class="Rrule" valign="bottom"><a name="figu"></a><img alt="Figure U" src="/dailymed/image.cfm?name=tyvasoDPI-39.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure U</span></td><td align="center" valign="bottom"><a name="figv"></a><img alt="Figure V" src="/dailymed/image.cfm?name=tyvasoDPI-40.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure V</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<thead>\n<tr>\n<th align=\"left\">Step 7: Inhale Your Dose</th><th align=\"left\" colspan=\"2\"></th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Rrule\"><span class=\"Bold\">Remove the Mouthpiece Cover</span> (see <span class=\"Bold\"><a href=\"#figt\">Figure T</a></span>).<br/>\n<span class=\"Bold\">Important:</span> Keep the inhaler level during and after removal of the blue mouthpiece cover to prevent loss of TYVASO DPI powder.</td><td align=\"left\" class=\"Rrule\"><span class=\"Bold\">Hold Inhaler Near Cheek</span>\n<br/> While keeping the inhaler level, carefully pick up the inhaler and bring it near your cheek, but not in front of your mouth (see <span class=\"Bold\"><a href=\"#figu\">Figure U</a></span>).</td><td align=\"left\"><span class=\"Bold\">Exhale</span>\n<br/> Holding the inhaler away from your mouth, fully blow out (exhale) (see <span class=\"Bold\"><a href=\"#figv\">Figure V</a></span>).</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\" valign=\"bottom\"><a name=\"figt\"></a><img alt=\"Figure T\" src=\"/dailymed/image.cfm?name=tyvasoDPI-38.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure T</span></td><td align=\"center\" class=\"Rrule\" valign=\"bottom\"><a name=\"figu\"></a><img alt=\"Figure U\" src=\"/dailymed/image.cfm?name=tyvasoDPI-39.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure U</span></td><td align=\"center\" valign=\"bottom\"><a name=\"figv\"></a><img alt=\"Figure V\" src=\"/dailymed/image.cfm?name=tyvasoDPI-40.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure V</span></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <tbody class="Headless"> <tr> <td align="left" class="Lrule"><span class="Bold">Position Inhaler in Mouth</span> <ul class="Disc"> <li>Keeping your head level, place the mouthpiece in your mouth and close your lips around the mouthpiece to form a seal.</li> <li>Tilt the inhaler slightly downward while keeping your head level (see <span class="Bold"><a href="#figw">Figure W</a></span>). <dl> <dt> </dt> <dd> <span class="Bold">Note:</span> This helps prevent the powder from being blocked by your tongue.</dd> </dl> </li> </ul> </td><td align="left" class="Lrule" colspan="3"><span class="Bold">Inhale Deeply, Hold Breath, then Exhale</span> <ul class="Disc"> <li>With your mouth closed around the mouthpiece, <span class="Bold">inhale</span> deeply through the inhaler (see <span class="Bold"><a href="#figx">Figure X</a></span>).</li> <li>Then remove the inhaler from your mouth and <span class="Bold">hold your breath</span> for as long as you comfortably can (see <span class="Bold"><a href="#figy">Figure Y</a></span>).</li> <li>Then <span class="Bold">blow out</span> (exhale) and continue to breathe normally (see <span class="Bold"><a href="#figz">Figure Z</a></span>).</li> </ul> </td> </tr> <tr> <td align="center" class="Lrule"><a name="figw"></a><img alt="Figure W" src="/dailymed/image.cfm?name=tyvasoDPI-41.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure W</span></td><td align="center" class="Lrule" valign="bottom"><a name="figx"></a><img alt="Figure X" src="/dailymed/image.cfm?name=tyvasoDPI-42.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure X</span></td><td align="center" class="Lrule" valign="bottom"><a name="figy"></a><img alt="Figure Y" src="/dailymed/image.cfm?name=tyvasoDPI-43.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure Y</span></td><td align="center" class="Lrule" valign="bottom"><a name="figz"></a><img alt="Figure Z" src="/dailymed/image.cfm?name=tyvasoDPI-44.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure Z</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<col align=\"center\" valign=\"top\" width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" class=\"Lrule\"><span class=\"Bold\">Position Inhaler in Mouth</span>\n<ul class=\"Disc\">\n<li>Keeping your head level, place the mouthpiece in your mouth and close your lips around the mouthpiece to form a seal.</li>\n<li>Tilt the inhaler slightly downward while keeping your head level (see <span class=\"Bold\"><a href=\"#figw\">Figure W</a></span>). \t\t\t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t\t\t<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> This helps prevent the powder from being blocked by your tongue.</dd>\n</dl>\n</li>\n</ul>\n</td><td align=\"left\" class=\"Lrule\" colspan=\"3\"><span class=\"Bold\">Inhale Deeply, Hold Breath, then Exhale</span>\n<ul class=\"Disc\">\n<li>With your mouth closed around the mouthpiece, <span class=\"Bold\">inhale</span> deeply through the inhaler (see <span class=\"Bold\"><a href=\"#figx\">Figure X</a></span>).</li>\n<li>Then remove the inhaler from your mouth and <span class=\"Bold\">hold your breath</span> for as long as you comfortably can (see <span class=\"Bold\"><a href=\"#figy\">Figure Y</a></span>).</li>\n<li>Then <span class=\"Bold\">blow out</span> (exhale) and continue to breathe normally (see <span class=\"Bold\"><a href=\"#figz\">Figure Z</a></span>).</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\"><a name=\"figw\"></a><img alt=\"Figure W\" src=\"/dailymed/image.cfm?name=tyvasoDPI-41.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure W</span></td><td align=\"center\" class=\"Lrule\" valign=\"bottom\"><a name=\"figx\"></a><img alt=\"Figure X\" src=\"/dailymed/image.cfm?name=tyvasoDPI-42.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure X</span></td><td align=\"center\" class=\"Lrule\" valign=\"bottom\"><a name=\"figy\"></a><img alt=\"Figure Y\" src=\"/dailymed/image.cfm?name=tyvasoDPI-43.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure Y</span></td><td align=\"center\" class=\"Lrule\" valign=\"bottom\"><a name=\"figz\"></a><img alt=\"Figure Z\" src=\"/dailymed/image.cfm?name=tyvasoDPI-44.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure Z</span></td>\n</tr>\n</tbody>\n</table></div>" }

Removing the Used Cartridge

{ "type": "p", "children": [], "text": "Removing the Used Cartridge" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <thead> <tr> <th align="left" colspan="4">Step 8 : Remove the used cartridge</th> </tr> </thead> <tbody> <tr> <td align="left" class="Rrule"><span class="Bold">Replace Mouthpiece Cover</span> <br/> Place the mouthpiece cover back onto the inhaler (see <span class="Bold"><a href="#figaa">Figure AA</a></span>). <dl> <dt> </dt> <dd> <span class="Bold">Note:</span> This keeps your fingers off the exposed mouthpiece.</dd> </dl> </td><td align="left" class="Rrule"><span class="Bold">Open Inhaler</span> <br/> Open the inhaler by lifting up the mouthpiece to an upright (vertical) position (see <span class="Bold"><a href="#figab">Figure AB</a></span>).</td><td align="left" colspan="2"><span class="Bold">Remove Cartridge</span> <ul class="Disc"> <li>Remove the used cartridge from the blue base (see <span class="Bold"><a href="#figac">Figure AC</a></span>).</li> <li>The cup should now be in the middle of the used cartridge (see <span class="Bold"><a href="#figad">Figure AD</a></span>).<dl> <dt> </dt> <dd> <span class="Bold">Warning:</span> If any powder from the cartridge spills on your hands, wash your hands right away.</dd> </dl> </li> </ul> </td> </tr> <tr> <td align="center" class="Rrule" rowspan="3" valign="bottom"><a name="figaa"></a><img alt="Figure AA" src="/dailymed/image.cfm?name=tyvasoDPI-45.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure AA</span></td><td align="center" class="Rrule" rowspan="3" valign="bottom"><a name="figab"></a><img alt="Figure AB" src="/dailymed/image.cfm?name=tyvasoDPI-46.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure AB</span></td><td align="center" rowspan="3" valign="bottom"><a name="figac"></a><img alt="Figure AC" src="/dailymed/image.cfm?name=tyvasoDPI-47.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure AC</span></td><td align="center" class="Lrule Rrule Toprule" valign="middle"><a name="figad"></a><img alt="Figure AD" src="/dailymed/image.cfm?name=tyvasoDPI-48.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="top">The cup moves to the middle of the cartridge when it has been used.</td> </tr> <tr> <td align="center" valign="bottom"><span class="Bold">Figure AD</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"4\">Step 8 : Remove the used cartridge</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Rrule\"><span class=\"Bold\">Replace Mouthpiece Cover</span>\n<br/> Place the mouthpiece cover back onto the inhaler (see <span class=\"Bold\"><a href=\"#figaa\">Figure AA</a></span>). \t\t\t\t\t\t\t\t\t\t \t\t\t\t\t\t\t\t\t\t<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Note:</span> This keeps your fingers off the exposed mouthpiece.</dd>\n</dl>\n</td><td align=\"left\" class=\"Rrule\"><span class=\"Bold\">Open Inhaler</span>\n<br/> Open the inhaler by lifting up the mouthpiece to an upright (vertical) position (see <span class=\"Bold\"><a href=\"#figab\">Figure AB</a></span>).</td><td align=\"left\" colspan=\"2\"><span class=\"Bold\">Remove Cartridge</span>\n<ul class=\"Disc\">\n<li>Remove the used cartridge from the blue base (see <span class=\"Bold\"><a href=\"#figac\">Figure AC</a></span>).</li>\n<li>The cup should now be in the middle of the used cartridge (see <span class=\"Bold\"><a href=\"#figad\">Figure AD</a></span>).<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Warning:</span> If any powder from the cartridge spills on your hands, wash your hands right away.</dd>\n</dl>\n</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Rrule\" rowspan=\"3\" valign=\"bottom\"><a name=\"figaa\"></a><img alt=\"Figure AA\" src=\"/dailymed/image.cfm?name=tyvasoDPI-45.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure AA</span></td><td align=\"center\" class=\"Rrule\" rowspan=\"3\" valign=\"bottom\"><a name=\"figab\"></a><img alt=\"Figure AB\" src=\"/dailymed/image.cfm?name=tyvasoDPI-46.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure AB</span></td><td align=\"center\" rowspan=\"3\" valign=\"bottom\"><a name=\"figac\"></a><img alt=\"Figure AC\" src=\"/dailymed/image.cfm?name=tyvasoDPI-47.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure AC</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" valign=\"middle\"><a name=\"figad\"></a><img alt=\"Figure AD\" src=\"/dailymed/image.cfm?name=tyvasoDPI-48.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"top\">The cup moves to the middle of the cartridge when it has been used.</td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"bottom\"><span class=\"Bold\">Figure AD</span></td>\n</tr>\n</tbody>\n</table></div>" }

Disposing of TYVASO DPI Cartridges

{ "type": "p", "children": [], "text": "Disposing of TYVASO DPI Cartridges" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="20%"/> <col align="left" valign="top" width="80%"/> <thead> <tr> <th align="left" class="Lrule" colspan="2">Step 9 : Throw away used cartridge</th> </tr> </thead> <tbody> <tr> <td align="left" class="Lrule" colspan="2">Throw away the used cartridge in your regular household trash (see <span class="Bold"><a href="#figae">Figure AE</a></span>).</td> </tr> <tr> <td align="center" class="Lrule"><a name="figae"></a><img alt="Figure AE" src="/dailymed/image.cfm?name=tyvasoDPI-49.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure AE</span></td><td align="left"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<thead>\n<tr>\n<th align=\"left\" class=\"Lrule\" colspan=\"2\">Step 9 : Throw away used cartridge</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\">Throw away the used cartridge in your regular household trash (see <span class=\"Bold\"><a href=\"#figae\">Figure AE</a></span>).</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule\"><a name=\"figae\"></a><img alt=\"Figure AE\" src=\"/dailymed/image.cfm?name=tyvasoDPI-49.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure AE</span></td><td align=\"left\"></td>\n</tr>\n</tbody>\n</table></div>" }

Inhaling Multiple Cartridges of TYVASO DPI

{ "type": "p", "children": [], "text": "Inhaling Multiple Cartridges of TYVASO DPI" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="28%"/> <col align="left" valign="top" width="27%"/> <col align="center" valign="top" width="3%"/> <col align="center" valign="top" width="32%"/> <col align="center" valign="top" width="10%"/> <thead> <tr> <th align="left" colspan="5">Step 10 : Inhaling multiple cartridges (skip if not needed)</th> </tr> </thead> <tbody> <tr> <td align="left" colspan="2">If your dose requires you to inhale multiple cartridges, <span class="Bold">repeat steps 6 through 9</span> for each cartridge.</td><td align="center" colspan="3"><span class="Bold">Warning:</span> Be careful not to mix NEW cartridges with used cartridges (see <span class="Bold"><a href="#figag">Figure AG</a></span>).</td> </tr> <tr> <td align="left" colspan="2"> <dl> <dt> </dt> <dd> <span class="Bold">Example:</span> If your prescribed TYVASO DPI dose is 96 mcg per treatment session, you can use one 32 mcg cartridge and one 64 mcg cartridge (see <span class="Bold"><a href="#figaf">Figure AF</a></span>):</dd> </dl> </td><td align="center"></td><td align="center" class="Lrule Rrule Toprule" valign="middle"><a name="figag"></a><img alt="Figure AG" src="/dailymed/image.cfm?name=tyvasoDPI-51.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></td><td align="center"></td> </tr> <tr> <td align="center"></td><td align="center"></td><td align="center"></td><td align="center" class="Botrule Lrule Rrule" valign="middle">The cup moves to the middle of the cartridge when it has been used.</td><td align="center"></td> </tr> <tr> <td align="center" colspan="2"><a name="figaf"></a><img alt="Figure AF" src="/dailymed/image.cfm?name=tyvasoDPI-50.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/><br/> <span class="Bold">Figure AF</span></td><td align="center"></td><td align="center"><span class="Bold">Figure AG</span></td><td align="center"></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"28%\"/>\n<col align=\"left\" valign=\"top\" width=\"27%\"/>\n<col align=\"center\" valign=\"top\" width=\"3%\"/>\n<col align=\"center\" valign=\"top\" width=\"32%\"/>\n<col align=\"center\" valign=\"top\" width=\"10%\"/>\n<thead>\n<tr>\n<th align=\"left\" colspan=\"5\">Step 10 : Inhaling multiple cartridges (skip if not needed)</th>\n</tr>\n</thead>\n<tbody>\n<tr>\n<td align=\"left\" colspan=\"2\">If your dose requires you to inhale multiple cartridges, <span class=\"Bold\">repeat steps 6 through 9</span> for each cartridge.</td><td align=\"center\" colspan=\"3\"><span class=\"Bold\">Warning:</span> Be careful not to mix NEW cartridges with used cartridges (see <span class=\"Bold\"><a href=\"#figag\">Figure AG</a></span>).</td>\n</tr>\n<tr>\n<td align=\"left\" colspan=\"2\">\n<dl>\n<dt> </dt>\n<dd>\n<span class=\"Bold\">Example:</span> If your prescribed TYVASO DPI dose is 96 mcg per treatment session, you can use one 32 mcg cartridge and one 64 mcg cartridge (see <span class=\"Bold\"><a href=\"#figaf\">Figure AF</a></span>):</dd>\n</dl>\n</td><td align=\"center\"></td><td align=\"center\" class=\"Lrule Rrule Toprule\" valign=\"middle\"><a name=\"figag\"></a><img alt=\"Figure AG\" src=\"/dailymed/image.cfm?name=tyvasoDPI-51.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></td><td align=\"center\"></td>\n</tr>\n<tr>\n<td align=\"center\"></td><td align=\"center\"></td><td align=\"center\"></td><td align=\"center\" class=\"Botrule Lrule Rrule\" valign=\"middle\">The cup moves to the middle of the cartridge when it has been used.</td><td align=\"center\"></td>\n</tr>\n<tr>\n<td align=\"center\" colspan=\"2\"><a name=\"figaf\"></a><img alt=\"Figure AF\" src=\"/dailymed/image.cfm?name=tyvasoDPI-50.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/><br/>\n<span class=\"Bold\">Figure AF</span></td><td align=\"center\"></td><td align=\"center\"><span class=\"Bold\">Figure AG</span></td><td align=\"center\"></td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table class="Noautorules" width="90%"> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <col align="left" valign="top" width="25%"/> <tbody class="Headless"> <tr> <td align="left" colspan="2">Caring for Your TYVASO DPI Inhaler</td><td align="left" colspan="2">Disposing of Your TYVASO DPI Inhaler</td> </tr> <tr> <td align="left" class="Lrule" colspan="2"><span class="Bold">Inhaler Care Instructions</span></td><td align="left" class="Lrule" colspan="2"><span class="Bold">Throw away used inhaler after 7 days of use</span></td> </tr> <tr> <td align="left" class="Lrule"><span class="Bold">Cleaning</span> <br/> After taking your dose, powder residue in the mouthpiece is normal; this will not affect your dose.</td><td align="left"><span class="Bold">Use Time</span> <br/> Only use 1 inhaler at a time.<br/> The same inhaler can be used to take 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg cartridges.</td><td align="left" class="Lrule" colspan="2">After 7 days of use, throw away the used inhaler in your regular household trash (see <span class="Bold"><a href="#figah">Figure AH</a></span> and <span class="Bold"><a href="#figai">Figure AI</a></span>).</td> </tr> <tr> <td align="left" class="Lrule">The outside of the inhaler can be wiped with a clean, dry cloth only, if needed.<br/> <span class="Bold">Never wash the inhaler.</span> <br/> Always keep the inhaler dry.</td><td align="left">Replace the inhaler after 7 days (see <span class="Bold"><a href="#figah">Figure AH</a></span> and <span class="Bold"><a href="#figai">Figure AI</a></span>). Keep track of 7 days from when you start using the inhaler with a calendar.</td><td align="center" class="Lrule" rowspan="2"> <p class="First"> <a name="figai"></a><img alt="Figure AI" src="/dailymed/image.cfm?name=tyvasoDPI-52.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></p> <br/> <span class="Bold">Figure AI</span></td><td align="left" rowspan="2"></td> </tr> <tr> <td align="left" class="Lrule"></td><td align="center"> <p class="First"> <a name="figah"></a><img alt="Figure AH" src="/dailymed/image.cfm?name=tyvasoDPI-53.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f"/></p> <br/> <span class="Bold">Figure AH</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"90%\">\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<col align=\"left\" valign=\"top\" width=\"25%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"left\" colspan=\"2\">Caring for Your TYVASO DPI Inhaler</td><td align=\"left\" colspan=\"2\">Disposing of Your TYVASO DPI Inhaler</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\" colspan=\"2\"><span class=\"Bold\">Inhaler Care Instructions</span></td><td align=\"left\" class=\"Lrule\" colspan=\"2\"><span class=\"Bold\">Throw away used inhaler after 7 days of use</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"><span class=\"Bold\">Cleaning</span>\n<br/> After taking your dose, powder residue in the mouthpiece is normal; this will not affect your dose.</td><td align=\"left\"><span class=\"Bold\">Use Time</span>\n<br/> Only use 1 inhaler at a time.<br/> The same inhaler can be used to take 16 mcg, 32 mcg, 48 mcg, 64 mcg, or 80 mcg cartridges.</td><td align=\"left\" class=\"Lrule\" colspan=\"2\">After 7 days of use, throw away the used inhaler in your regular household trash (see <span class=\"Bold\"><a href=\"#figah\">Figure AH</a></span> and <span class=\"Bold\"><a href=\"#figai\">Figure AI</a></span>).</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\">The outside of the inhaler can be wiped with a clean, dry cloth only, if needed.<br/>\n<span class=\"Bold\">Never wash the inhaler.</span>\n<br/> Always keep the inhaler dry.</td><td align=\"left\">Replace the inhaler after 7 days (see <span class=\"Bold\"><a href=\"#figah\">Figure AH</a></span> and <span class=\"Bold\"><a href=\"#figai\">Figure AI</a></span>). Keep track of 7 days from when you start using the inhaler with a calendar.</td><td align=\"center\" class=\"Lrule\" rowspan=\"2\">\n<p class=\"First\">\n<a name=\"figai\"></a><img alt=\"Figure AI\" src=\"/dailymed/image.cfm?name=tyvasoDPI-52.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></p>\n<br/>\n<span class=\"Bold\">Figure AI</span></td><td align=\"left\" rowspan=\"2\"></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\"></td><td align=\"center\">\n<p class=\"First\">\n<a name=\"figah\"></a><img alt=\"Figure AH\" src=\"/dailymed/image.cfm?name=tyvasoDPI-53.jpg&amp;setid=ddc3d400-bcb3-4b09-aae2-0768b10a5b0f\"/></p>\n<br/>\n<span class=\"Bold\">Figure AH</span></td>\n</tr>\n</tbody>\n</table></div>" }

For further questions and information, or to report a problem with your device or any side effects with your TYVASO DPI, please call 1-844-UNITHER (1-844-864-8437).

{ "type": "p", "children": [], "text": "For further questions and information, or to report a problem with your device or any side effects with your TYVASO DPI, please call 1-844-UNITHER (1-844-864-8437)." }

This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: October 2024

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: October 2024" }

TYVASO DPI® is a registered trademark of United Therapeutics Corporation.

{ "type": "p", "children": [], "text": "TYVASO DPI® is a registered trademark of United Therapeutics Corporation." }

Patents: www.tyvasodpi.com/patent

{ "type": "p", "children": [], "text": "Patents: www.tyvasodpi.com/patent" }

Distributed by: United Therapeutics Corporation Research Triangle Park, NC 27709 USA

{ "type": "p", "children": [], "text": "Distributed by: United Therapeutics Corporation Research Triangle Park, NC 27709 USA" }

Manufactured by: MannKind Corporation Danbury, CT 06810 USA

{ "type": "p", "children": [], "text": "Manufactured by: MannKind Corporation Danbury, CT 06810 USA" }

10/202430-1311-006-03

{ "type": "p", "children": [], "text": "10/202430-1311-006-03" }

NDC 66302-616-03 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-616-03 Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 16 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 16 mcg per cartridge + 5 Inhalers" }

This MAINTENANCE KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

16 mcg per cartridge

{ "type": "p", "children": [], "text": "16 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-716-04 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-716-04 Rx ONLY" }

Institutional Kit

{ "type": "p", "children": [], "text": "Institutional Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

16 cartridges, each containing 16 mcg per cartridge + 2 Inhalers

{ "type": "p", "children": [], "text": "16 cartridges, each containing 16 mcg per cartridge + 2 Inhalers" }

This INSTITUTIONAL KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This INSTITUTIONAL KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

16 mcg per cartridge

{ "type": "p", "children": [], "text": "16 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-632-03 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-632-03 Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 32 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 32 mcg per cartridge + 5 Inhalers" }

This MAINTENANCE KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

32 mcg per cartridge

{ "type": "p", "children": [], "text": "32 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-732-04 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-732-04 Rx ONLY" }

Institutional Kit

{ "type": "p", "children": [], "text": "Institutional Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

16 cartridges, each containing 32 mcg per cartridge + 2 Inhalers

{ "type": "p", "children": [], "text": "16 cartridges, each containing 32 mcg per cartridge + 2 Inhalers" }

This INSTITUTIONAL KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This INSTITUTIONAL KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

32 mcg per cartridge

{ "type": "p", "children": [], "text": "32 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-648-03 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-648-03 Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 48 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 48 mcg per cartridge + 5 Inhalers" }

This MAINTENANCE KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

48 mcg per cartridge

{ "type": "p", "children": [], "text": "48 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-748-04 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-748-04 Rx ONLY" }

Institutional Kit

{ "type": "p", "children": [], "text": "Institutional Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

16 cartridges, each containing 48 mcg per cartridge + 2 Inhalers

{ "type": "p", "children": [], "text": "16 cartridges, each containing 48 mcg per cartridge + 2 Inhalers" }

This INSTITUTIONAL KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This INSTITUTIONAL KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

48 mcg per cartridge

{ "type": "p", "children": [], "text": "48 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-664-03 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-664-03 Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 64 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 64 mcg per cartridge + 5 Inhalers" }

This MAINTENANCE KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

64 mcg per cartridge

{ "type": "p", "children": [], "text": "64 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-764-04 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-764-04 Rx ONLY" }

Institutional Kit

{ "type": "p", "children": [], "text": "Institutional Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

16 cartridges, each containing 64 mcg per cartridge + 2 Inhalers

{ "type": "p", "children": [], "text": "16 cartridges, each containing 64 mcg per cartridge + 2 Inhalers" }

This INSTITUTIONAL KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This INSTITUTIONAL KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

64 mcg per cartridge

{ "type": "p", "children": [], "text": "64 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-680-03Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-680-03Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLYKIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLYKIT CONTAINS:" }

112 cartridges, each containing80 mcg per cartridge + 5Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing80 mcg per cartridge + 5Inhalers" }

This MAINTENANCE KIT is NOT intendedfor initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intendedfor initial titration." }

TYVASO DPI® (treprostinil)INHALATIONPOWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n(treprostinil)INHALATIONPOWDER" }

80mcg percartridge

{ "type": "p", "children": [], "text": "80mcg percartridge" }

BLISTER STORAGEUnopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discardunopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGEUnopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discardunopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-780-04 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-780-04 Rx ONLY" }

Institutional Kit

{ "type": "p", "children": [], "text": "Institutional Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

16 cartridges, each containing 80 mcg per cartridge + 2 Inhalers

{ "type": "p", "children": [], "text": "16 cartridges, each containing 80 mcg per cartridge + 2 Inhalers" }

This INSTITUTIONAL KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This INSTITUTIONAL KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

80 mcg per cartridge

{ "type": "p", "children": [], "text": "80 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-600-02 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-600-02 Rx ONLY" }

Titration Kit

{ "type": "p", "children": [], "text": "Titration Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 16 mcg per cartridge 84 cartridges, each containing 32 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 16 mcg per cartridge 84 cartridges, each containing 32 mcg per cartridge + 5 Inhalers" }

TYVASO DPI™ (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI™ (treprostinil) INHALATION POWDER" }

16 mcg per cartridge 32 mcg per cartridge

{ "type": "p", "children": [], "text": "16 mcg per cartridge 32 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 5 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 5 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-620-03 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-620-03 Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 32 mcg per cartridge 112 cartridges, each containing 48 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 32 mcg per cartridge 112 cartridges, each containing 48 mcg per cartridge + 5 Inhalers" }

This MAINTENANCE KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

32 mcg per cartridge 48 mcg per cartridge

{ "type": "p", "children": [], "text": "32 mcg per cartridge 48 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-630-03Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-630-03Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLYKIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLYKIT CONTAINS:" }

112 cartridges, each containing32 mcg per cartridge 112 cartridges, each containing64 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing32 mcg per cartridge 112 cartridges, each containing64 mcg per cartridge + 5 Inhalers" }

This MAINTENANCE KIT is NOT intendedfor initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intendedfor initial titration." }

TYVASO DPI® (treprostinil)INHALATIONPOWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n(treprostinil)INHALATIONPOWDER" }

32mcg percartridge64mcg percartridge

{ "type": "p", "children": [], "text": "32mcg percartridge64mcg percartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-640-03Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-640-03Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLYKIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLYKIT CONTAINS:" }

112 cartridges, each containing48 mcg per cartridge 112 cartridges, each containing64 mcg per cartridge + 5Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing48 mcg per cartridge 112 cartridges, each containing64 mcg per cartridge + 5Inhalers" }

This MAINTENANCE KIT is NOT intendedfor initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intendedfor initial titration." }

TYVASO DPI® (treprostinil)INHALATIONPOWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n(treprostinil)INHALATIONPOWDER" }

48mcg percartridge64mcg percartridge

{ "type": "p", "children": [], "text": "48mcg percartridge64mcg percartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-720-04 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-720-04 Rx ONLY" }

Institutional Kit

{ "type": "p", "children": [], "text": "Institutional Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

16 cartridges, each containing 32 mcg per cartridge 16 cartridges, each containing 48 mcg per cartridge + 2 Inhalers

{ "type": "p", "children": [], "text": "16 cartridges, each containing 32 mcg per cartridge 16 cartridges, each containing 48 mcg per cartridge + 2 Inhalers" }

This INSTITUTIONAL KIT is NOT intended for initial titration.

{ "type": "p", "children": [], "text": "This INSTITUTIONAL KIT is NOT intended for initial titration." }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

32 mcg per cartridge 48 mcg per cartridge

{ "type": "p", "children": [], "text": "32 mcg per cartridge 48 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-610-02 Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-610-02 Rx ONLY" }

Titration Kit

{ "type": "p", "children": [], "text": "Titration Kit" }

FOR ORAL INHALATION ONLY KIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY KIT CONTAINS:" }

112 cartridges, each containing 16 mcg per cartridge 112 cartridges, each containing 32 mcg per cartridge 28 cartridges, each containing 48 mcg per cartridge + 5 Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing 16 mcg per cartridge 112 cartridges, each containing 32 mcg per cartridge 28 cartridges, each containing 48 mcg per cartridge + 5 Inhalers" }

TYVASO DPI® (treprostinil) INHALATION POWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n (treprostinil) INHALATION POWDER" }

16 mcg per cartridge 32 mcg per cartridge 48 mcg per cartridge

{ "type": "p", "children": [], "text": "16 mcg per cartridge 32 mcg per cartridge 48 mcg per cartridge" }

BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGE Unopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discard unopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

NDC 66302-650-03Rx ONLY

{ "type": "p", "children": [], "text": "NDC 66302-650-03Rx ONLY" }

Maintenance Kit

{ "type": "p", "children": [], "text": "Maintenance Kit" }

FOR ORAL INHALATION ONLYKIT CONTAINS:

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLYKIT CONTAINS:" }

112 cartridges, each containing16 mcg per cartridge 112 cartridges, each containing48 mcg per cartridge112 cartridges, each containing64 mcg per cartridge + 5Inhalers

{ "type": "p", "children": [], "text": "112 cartridges, each containing16 mcg per cartridge 112 cartridges, each containing48 mcg per cartridge112 cartridges, each containing64 mcg per cartridge + 5Inhalers" }

This MAINTENANCE KIT is NOT intendedfor initial titration.

{ "type": "p", "children": [], "text": "This MAINTENANCE KIT is NOT intendedfor initial titration." }

TYVASO DPI® (treprostinil)INHALATIONPOWDER

{ "type": "p", "children": [], "text": "TYVASO DPI®\n(treprostinil)INHALATIONPOWDER" }

16mcg percartridge48mcg percartridge64mcg percartridge

{ "type": "p", "children": [], "text": "16mcg percartridge48mcg percartridge64mcg percartridge" }

BLISTER STORAGEUnopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discardunopened blister strips stored at room temperature after 8 weeks.

{ "type": "p", "children": [], "text": "BLISTER STORAGEUnopened Blister Cards/Strips: Store refrigerated at 2°C to 8°C (36°F to 46°F). Discardunopened blister strips stored at room temperature after 8 weeks." }

Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening.

{ "type": "p", "children": [], "text": "Opened Blister Strips: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Discard opened blister strips holding unused cartridges 3 days after opening." }

INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use.

{ "type": "p", "children": [], "text": "INHALER STORAGE Store at 2°C to 25°C (36°F to 77°F) excursions permitted. May be stored refrigerated, but must be at room temperature before use." }

The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler.

{ "type": "p", "children": [], "text": "The inhaler can be used for up to 7 days from the date of first use. After 7 days of use, discard the used inhaler and replace with a new inhaler." }

YUTREPIA is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).

The effects diminish over the minimum recommended dosing interval of 4 hours; treatment timing can be adjusted for planned activities.

While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration [see Clinical Studies (14)].

YUTREPIA is indicated for the treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability. The study establishing effectiveness predominately included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE) (25%), and WHO Group 3 connective tissue disease (22%) [see Clinical Studies (14.2)].

YUTREPIA capsules are for oral inhalation only and should be used only with the supplied inhaler. Do not swallow YUTREPIA capsules.

YUTREPIA Dosing in treprostinil-naïve patients:

In patients naïve to treprostinil, therapy should begin with 26.5 mcg 3 to 5 times per day, in 2 breaths based on patient response.

Dosing in patients transitioning from treprostinil inhalation solution (Tyvaso):

Patients transitioning from treprostinil inhalation solution (Tyvaso), can begin YUTREPIA therapy 3 to 5 times per day, in 2 breaths, using the doses specified below (Table 1):

<div class="scrollingtable"><table cellpadding="3.6pt" width="50%"> <caption> <span>Table 1: YUTREPIA Dosing in Patients Transitioning from Treprostinil Inhalation Solution</span> </caption> <col width="28%"/> <col width="28%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="2" valign="top">*Each breath of Tyvaso delivers approximately 6 mcg of treprostinil.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" valign="middle"> <p class="First"> <span class="Bold">Current Tyvaso Dose*</span> </p> </td><td align="center" valign="middle"> <p class="First"> <span class="Bold">YUTREPIA Dose</span> </p> </td> </tr> <tr> <td align="center" class="Botrule" valign="middle"> <p class="First"> <span class="Bold">(Number of Breaths)</span> </p> </td><td align="center" class="Botrule" valign="middle"> <p class="First"> <span class="Bold">mcg</span> </p> </td> </tr> <tr> <td align="center" class="Toprule" valign="middle"> <p class="First">5 or less breaths</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">26.5 mcg</p> </td> </tr> <tr> <td align="center" valign="middle"> <p class="First">6 to 8 breaths</p> </td><td align="center" valign="top"> <p class="First">53 mcg</p> </td> </tr> <tr> <td align="center" valign="middle"> <p class="First">9 to 11 breaths</p> </td><td align="center" valign="top"> <p class="First">79.5 mcg</p> </td> </tr> <tr> <td align="center" valign="middle"> <p class="First">12 to 14 breaths</p> </td><td align="center" valign="top"> <p class="First">106 mcg</p> </td> </tr> <tr> <td align="center" valign="middle"> <p class="First">15 to 17 breaths</p> </td><td align="center" valign="top"> <p class="First">132.5 mcg</p> </td> </tr> <tr class="Last"> <td align="center" valign="middle"> <p class="First">18 or more breaths</p> </td><td align="center" valign="top"> <p class="First">159 mcg</p> </td> </tr> </tbody> </table></div>

In treprostinil-naïve patients and those transitioning from treprostinil inhalation solution, dose increases of 26.5 mcg per dose each week may be implemented, as tolerated. The target maintenance dosage is 79.5 mcg to 106 mcg, 4 times daily.

Doses above 848 mcg per day have not been studied in patients with PAH.

If a scheduled dose is missed, resume therapy as soon as possible at the usual dose.

YUTREPIA inhalation powder contained in capsule available in 4 strengths:

{ "type": "p", "children": [], "text": "YUTREPIA inhalation powder contained in capsule available in 4 strengths:" }

{ "type": "", "children": [], "text": "" }

None

{ "type": "p", "children": [], "text": "None" }

Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with treprostinil may produce symptomatic hypotension.

Treprostinil inhibits platelet aggregation and increases the risk of bleeding.

Co-administration of a cytochrome P450 (CYP) 2C8 enzyme inhibitor (e.g., gemfibrozil) may increase exposure (both Cmax and AUC) to treprostinil. Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. Increased exposure is likely to increase adverse events associated with treprostinil administration, whereas decreased exposure is likely to reduce clinical effectiveness [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Like other inhaled prostaglandins, YUTREPIA may cause acute bronchospasm. Patients with asthma or chronic obstructive pulmonary disease (COPD), or other bronchial hyperreactivity, are at increased risk for bronchospasm. Ensure that such patients are treated optimally for reactive airway disease prior to and during treatment with YUTREPIA.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety and tolerability of YUTREPIA was evaluated in an open label study (INSPIRE) of 121 patients with PAH (WHO Group 1 and NYHA Functional Class II [80 patients] and Class III [41 patients]) followed for up to 2 months. The most commonly reported adverse reactions included cough, headache, throat irritation, dizziness, which are known side effects of treprostinil inhalation solution. Table 2 lists the adverse reactions that occurred at a rate of at least 4% of the overall INSPIRE safety population. The adverse reactions in the INSPIRE study were consistent with those observed in previous studies of inhaled treprostinil.

<div class="scrollingtable"><table cellpadding="3.6pt" width="50%"> <caption> <span>Table 2: Adverse Reactions Occurring in ≥ 4% of Patients in the INSPIRE Study</span> </caption> <col width="23%"/> <col width="17%"/> <col width="17%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="3" valign="top">*Transition: Patients were on stable doses of treprostinil inhalation solution for at least 3 months prior to enrollment in the study and transitioned to treatment with YUTREPIA.<br/>†Add-on: Patients were prostacyclin-naïve and were taking no more than 2 approved oral PAH therapies for at least 3 months at time of enrollment and addition of treatment with YUTREPIA.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td rowspan="2" valign="bottom"> <p class="First"> <span class="Bold">Adverse Reaction</span> </p> </td><td align="center" valign="bottom"> <p class="First"> <span class="Bold">Transition*<br/>N=55</span> </p> </td><td align="center" valign="bottom"> <p class="First"> <span class="Bold">Add-On†<br/>N=66</span> </p> </td> </tr> <tr> <td align="center" class="Botrule" valign="bottom"> <p class="First"> <span class="Bold">n (%)</span> </p> </td><td align="center" class="Botrule" valign="bottom"> <p class="First"> <span class="Bold">n (%)</span> </p> </td> </tr> <tr> <td class="Toprule" valign="bottom"> <p class="First">Cough</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">15 (27)</p> </td><td align="center" class="Toprule" valign="top"> <p class="First">36 (55)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Headache</p> </td><td align="center" valign="top"> <p class="First">14 (25)</p> </td><td align="center" valign="top"> <p class="First">18 (27)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Throat Irritation</p> </td><td align="center" valign="top"> <p class="First">5 (9)</p> </td><td align="center" valign="top"> <p class="First">14 (21)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Dizziness</p> </td><td align="center" valign="top"> <p class="First">6 (11)</p> </td><td align="center" valign="top"> <p class="First">7 (11)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Diarrhea</p> </td><td align="center" valign="top"> <p class="First">3 (6)</p> </td><td align="center" valign="top"> <p class="First">8 (12)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Chest Discomfort</p> </td><td align="center" valign="top"> <p class="First">5 (9)</p> </td><td align="center" valign="top"> <p class="First">5 (8)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Nausea</p> </td><td align="center" valign="top"> <p class="First">4 (7)</p> </td><td align="center" valign="top"> <p class="First">5 (8)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Dyspnea</p> </td><td align="center" valign="top"> <p class="First">3 (6)</p> </td><td align="center" valign="top"> <p class="First">3 (5)</p> </td> </tr> <tr> <td valign="bottom"> <p class="First">Flushing</p> </td><td align="center" valign="top"> <p class="First">1 (2)</p> </td><td align="center" valign="top"> <p class="First">5 (8)</p> </td> </tr> <tr class="Last"> <td valign="bottom"> <p class="First">Oropharyngeal Pain</p> </td><td align="center" valign="top"> <p class="First">1 (2)</p> </td><td align="center" valign="top"> <p class="First">4 (6)</p> </td> </tr> </tbody> </table></div>

The following adverse reaction has been identified during the post-approval use of treprostinil inhalation solution. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure:

In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A.

Additionally, treprostinil does not induce cytochrome P450 isoenzymes CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A.

Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to treprostinil. It is unclear if the safety and efficacy of treprostinil by the inhalation route are altered by inhibitors or inducers of CYP2C8 [see Warnings and Precautions (5.3)].

Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively, in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S- warfarin and the INR in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.

Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. However, there are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations). In animal studies, no adverse reproductive and developmental effects were seen for treprostinil at 39 and 3145 times the human exposure when based on Cmax and AUC, respectively, following a single YUTREPIA dose of 79.5 mcg [see Clinical Pharmacology (12.3)].

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Disease-associated maternal and embryo-fetal risk

Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality.

Animal reproduction studies have been conducted with treprostinil via continuous subcutaneous administration and with treprostinil diolamine administered orally. In studies with orally administered treprostinil diolamine, no adverse effect doses for fetal viability/growth, fetal development (teratogenicity), and postnatal development were determined in rats. In pregnant rats, no evidence of harm to the fetus was observed following oral administration of treprostinil diolamine at the highest dose tested (20 mg/kg/day), which represents about 154 and 1479 times the human exposure, when based on Cmax and AUC, respectively, following a single YUTREPIA dose of 79.5 mcg. In pregnant rabbits, external fetal and soft tissue malformations and fetal skeletal malformation occurred. The dose at which no adverse effects were seen (0.5 mg/kg/day) represents about 9 and 145 times the human exposure, when based on Cmax and AUC, respectively, following a single YUTREPIA dose of 79.5 mcg. No treprostinil treatment-related effects on labor and delivery were seen in animal studies. Animal reproduction studies are not always predictive of human response.

There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.

Safety and effectiveness in pediatric patients have not been established.

Placebo-controlled clinical studies of treprostinil inhalation solution did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. The open-label INSPIRE study in PAH patients included 28 patients aged 65 and over in which no age-related differences were noted. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of hepatic, renal, or cardiac dysfunction, and of concomitant diseases or other drug therapy.

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects with mild-to-moderate hepatic insufficiency. Uptitrate slowly when treating patients with hepatic insufficiency because of the risk of an increase in systemic exposure which may lead to an increase in dose-dependent adverse effects. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Clinical Pharmacology (12.3)].

No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis [see Clinical Pharmacology (12.3)].

In general, symptoms of overdose with treprostinil include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved.

{ "type": "p", "children": [], "text": "In general, symptoms of overdose with treprostinil include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Provide general supportive care until the symptoms of overdose have resolved." }

YUTREPIA contains treprostinil sodium, a prostacyclin mimetic. The chemical name for tresprostinil sodium is 2-{[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H,2H,3H,3aH,4H,9H,9aH-cyclopenta[b]naphthalen-5-yl]oxy}acetic acid, sodium salt with the structural formula:

{ "type": "p", "children": [], "text": "YUTREPIA contains treprostinil sodium, a prostacyclin mimetic. The chemical name for tresprostinil sodium is 2-{[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H,2H,3H,3aH,4H,9H,9aH-cyclopenta[b]naphthalen-5-yl]oxy}acetic acid, sodium salt with the structural formula:" }

Treprostinil sodium has a molecular formula of C23H33O5Na and a molecular weight of 412.49 daltons equivalent to 390.5 daltons of Treprostinil.

{ "type": "p", "children": [], "text": "Treprostinil sodium has a molecular formula of C23H33O5Na and a molecular weight of 412.49 daltons equivalent to 390.5 daltons of Treprostinil. " }

YUTREPIA inhalation powder contained in a capsule is intended for oral inhalation. The capsule contains white to off-white powder of treprostinil sodium and the inactive ingredients L-leucine, polysorbate 80, sodium chloride, sodium citrate, and trehalose. Each 5 mg of YUTREPIA inhalation powder contains 26.5 mcg of treprostinil, where 26.5 mcg of treprostinil is equivalent to 28 mcg of treprostinil sodium.

{ "type": "p", "children": [], "text": "YUTREPIA inhalation powder contained in a capsule is intended for oral inhalation. The capsule contains white to off-white powder of treprostinil sodium and the inactive ingredients L-leucine, polysorbate 80, sodium chloride, sodium citrate, and trehalose. Each 5 mg of YUTREPIA inhalation powder contains 26.5 mcg of treprostinil, where 26.5 mcg of treprostinil is equivalent to 28 mcg of treprostinil sodium. " }

The accompanying inhalation device for delivery of YUTREPIA inhalation powder is a disposable plastic device used to inhale the dry powder contained in the HPMC capsule.

{ "type": "p", "children": [], "text": "The accompanying inhalation device for delivery of YUTREPIA inhalation powder is a disposable plastic device used to inhale the dry powder contained in the HPMC capsule. " }

The amount of drug delivered to the lungs will vary depending on patient factors such as inspiratory flow and peak inspiratory flow through the inhalation device, which may vary from patient to patient.

{ "type": "p", "children": [], "text": "The amount of drug delivered to the lungs will vary depending on patient factors such as inspiratory flow and peak inspiratory flow through the inhalation device, which may vary from patient to patient. " }

Under standardized in vitro testing, the inhalation device delivers the following amounts of treprostinil for each of the YUTREPIA inhalation powder capsule strengths:

{ "type": "p", "children": [], "text": "Under standardized in vitro testing, the inhalation device delivers the following amounts of treprostinil for each of the YUTREPIA inhalation powder capsule strengths: " }

YUTREPIA Inhalation Powder Delivered Dose

{ "type": "p", "children": [], "text": "\nYUTREPIA Inhalation Powder Delivered Dose\n" }

<div class="scrollingtable"><table cellpadding="3.6pt" width="50%"> <col width="28%"/> <col width="28%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="2" valign="top"><span class="Sup">a </span>Amount of treprostinil delivered from the device mouthpiece under an <span class="Italics">in vitro</span> flow rate of 99 L/min with a collection time of 1.2 seconds (2 L total volume).</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule" valign="middle"> <p class="First"> <span class="Bold">Capsule Strength <br/>(treprostinil)</span> </p> </td><td align="center" class="Botrule" valign="middle"> <p class="First"> <span class="Bold">Dose Delivered <span class="Sup">a</span></span> </p> </td> </tr> <tr> <td align="center" class="Toprule" valign="middle"> <p class="First">26.5 mcg</p> </td><td align="center" class="Toprule" valign="middle"> <p class="First">15.1 mcg</p> </td> </tr> <tr> <td align="center" valign="middle"> <p class="First">53 mcg</p> </td><td align="center" valign="middle"> <p class="First">36.0 mcg</p> </td> </tr> <tr> <td align="center" valign="middle"> <p class="First">79.5 mcg</p> </td><td align="center" valign="middle"> <p class="First">56.6 mcg</p> </td> </tr> <tr class="Last"> <td align="center" valign="middle"> <p class="First">106 mcg</p> </td><td align="center" valign="middle"> <p class="First">75.7 mcg</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"3.6pt\" width=\"50%\">\n<col width=\"28%\"/>\n<col width=\"28%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\" valign=\"top\"><span class=\"Sup\">a </span>Amount of treprostinil delivered from the device mouthpiece under an <span class=\"Italics\">in vitro</span> flow rate of 99 L/min with a collection time of 1.2 seconds (2 L total volume).</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Capsule Strength <br/>(treprostinil)</span>\n</p>\n</td><td align=\"center\" class=\"Botrule\" valign=\"middle\">\n<p class=\"First\">\n<span class=\"Bold\">Dose Delivered <span class=\"Sup\">a</span></span>\n</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Toprule\" valign=\"middle\">\n<p class=\"First\">26.5 mcg</p>\n</td><td align=\"center\" class=\"Toprule\" valign=\"middle\">\n<p class=\"First\">15.1 mcg</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"middle\">\n<p class=\"First\">53 mcg</p>\n</td><td align=\"center\" valign=\"middle\">\n<p class=\"First\">36.0 mcg</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" valign=\"middle\">\n<p class=\"First\">79.5 mcg</p>\n</td><td align=\"center\" valign=\"middle\">\n<p class=\"First\">56.6 mcg</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" valign=\"middle\">\n<p class=\"First\">106 mcg</p>\n</td><td align=\"center\" valign=\"middle\">\n<p class=\"First\">75.7 mcg</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.

In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed. Treprostinil produces vasodilation and tachycardia.

Cardiac Electrophysiology

In a clinical trial of 240 healthy volunteers, single doses of treprostinil inhalation solution 54 mcg (the target maintenance dose per session) and 84 mcg (supratherapeutic inhalation dose) prolonged the corrected QTc interval by approximately 10 ms. The QTc effect dissipated rapidly as the concentration of treprostinil decreased.

Absorption

In healthy volunteer studies, the systemic exposure (AUC and Cmax) post-inhalation was shown to be proportional to the YUTREPIA doses administered (25 mcg – 150 mcg). The treprostinil mean Cmax, mean AUCinf and median Tmax following a single inhaled target maintenance dose of 79.5 mcg YUTREPIA were 1.48 ng/mL, 1.04 hr.ng/mL and 0.13 hr, respectively.

Distribution

In vitro treprostinil is 91% bound to human plasma proteins over the 330-10,000 ng/mL concentration range.

Metabolism and Excretion

Of subcutaneously administered treprostinil, only 4% is excreted unchanged in urine. Treprostinil is substantially metabolized by the liver, primarily by CYP2C8. Metabolites are excreted in urine (79%) and feces (13%) over 10 days. Five apparently inactive metabolites were detected in the urine, each accounting for 10‑15% of the dose administered. Four of the metabolites are products of oxidation of the 3-hydroxyloctyl side chain and one is a glucuroconjugated derivative (treprostinil glucuronide).

Elimination

Following inhaled administration of YUTREPIA, disposition and elimination is monophasic with a half-life of approximately 30 minutes.

Specific Populations

Hepatic Insufficiency

Plasma clearance of treprostinil, delivered subcutaneously, was reduced up to 80% in subjects presenting with mild-to-moderate hepatic insufficiency. Treprostinil has not been studied in patients with severe hepatic insufficiency [see Use in Specific Populations (8.6)].

Renal Insufficiency

In patients with severe renal impairment requiring dialysis (n=8), administration of a single 1 mg dose of orally administered treprostinil pre-and post-dialysis resulted in AUC0-inf that was not significantly altered compared to healthy subjects [see Use in Specific Populations (8.7)].

Carcinogenesis

A two-year rat carcinogenicity study was performed with treprostinil inhalation solution at target treprostinil doses of 5.26, 10.6, and 34.1 mcg/kg/day. There was no evidence for carcinogenic potential associated with treprostinil inhalation in rats at systemic exposure levels up to 35 times following a single YUTREPIA dose of 79.5 mcg [see Clinical Pharmacology (12.3)]. In vitro and in vivo genetic toxicology studies did not demonstrate any mutagenic or clastogenic effects of treprostinil. Treprostinil sodium did not affect fertility or mating performance of male or female rats given continuous subcutaneous (sc) infusions at rates of up to 450 ng treprostinil/kg/min. In this study, males were dosed from 10 weeks prior to mating and through the 2-week mating period. Females were dosed from 2 weeks prior to mating until gestational day 6.

Oral administration of treprostinil diolamine to Tg.rasH2 mice at 0, 5, 10 and 20 mg/kg/day in males and 0, 3, 7.5 and 15 mg/kg/day in females daily for 26 weeks did not significantly increase the incidence of tumors.

Treprostinil diolamine was tested in vivo in a rat micronucleus assay and did not induce an increased incidence of micronucleated polychromatic erythrocytes.

In a 2-year rat study with treprostinil inhalation at target doses of 5.26, 10.6, and 34.1 mcg/kg/day, there were more deaths (11) in the mid- and high-dose treprostinil groups during the first 9 weeks of the study, compared to 1 in control groups. At the high-dose level, males showed a higher incidence of inflammation in teeth and preputial gland, and females showed high incidences of inflammation and urothelial hyperplasia in the urinary bladder. The exposures in rats at mid- and high-dose levels were about 15 and 35 times, respectively, the clinical exposure following a single YUTREPIA dose of 79.5 mcg [see Clinical Pharmacology (12.3)].

TRIUMPH I was a 12-week, randomized, double-blind, placebo-controlled multi-center study of patients with PAH. The study population included 235 clinically stable patients with pulmonary arterial hypertension (WHO Group 1), nearly all with NYHA Class III (98%) symptoms who were receiving either bosentan (an endothelin receptor antagonist) or sildenafil (a phosphodiesterase-5 inhibitor) for at least three months prior to study initiation. Concomitant therapy also could have included anticoagulants, other vasodilators (e.g., calcium channel blockers), diuretics, oxygen, and digitalis, but not a prostacyclin. These patients were administered either placebo or treprostinil inhalation solution in four daily treatment sessions with a target dose of 9 breaths (equivalent to 79.5 mcg YUTREPIA) per session over the course of the 12-week study. Patients were predominantly female (82%), had the origin of PAH as idiopathic/heritable (56%), secondary to connective tissue diseases (33%) or secondary to HIV or previous use of anorexigens (12%); bosentan was the concomitant oral medication in 70% of those enrolled, sildenafil in 30%.

The primary efficacy endpoint of the trial was the change in six-minute walk distance (6MWD) relative to baseline at 12 weeks. 6MWD was measured at peak exposure (between 10 and 60 minutes after dosing), and 3‑5 hours after bosentan or 0.5-2 hours after sildenafil. Patients receiving treprostinil inhalation solution had a placebo-corrected median change from baseline in peak 6MWD of 20 meters at Week 12 (p<0.001).

The distribution of these 6MWD changes from baseline at Week 12 were plotted across the range of observed values (Figure 1). 6MWD measured at trough exposure (defined as measurement of 6MWD at least 4 hours after dosing) improved by 14 meters. There were no placebo-controlled 6MWD assessments made after 12 weeks.

The placebo-corrected median treatment effect on 6MWD was estimated (using the Hodges-Lehmann estimator) within various subpopulations defined by age quartile, gender, geographic region of the study site, disease etiology, baseline 6MWD quartile, and type of background therapy (Figure 2).

INCREASE was a 16-week, randomized, double-blind, placebo-controlled, multicenter study that enrolled 326 patients with PH-ILD. Enrolled study patients predominately had etiologies of idiopathic interstitial pneumonia (45%) inclusive of idiopathic pulmonary fibrosis, combined pulmonary fibrosis and emphysema (25%), and WHO Group 3 connective tissue disease (22%). The mean baseline 6MWD was 260 meters.

Patients in the INCREASE study were randomized (1:1) to either placebo or treprostinil inhalation solution in four daily treatment sessions with a target dose of 9 breaths (equivalent to 79.5 mcg YUTREPIA) per session and a maximum dose of 12 breaths (equivalent to 106 mcg YUTREPIA) per session over the course of the 16-week study. Approximately 75% of patients randomized to treprostinil inhalation solution titrated up to a dose of 9 breaths, 4 times daily or greater, with 48% of patients randomized to treprostinil inhalation solution reaching a dose of 12 breaths, 4 times daily during the study. The primary efficacy endpoint was the change in 6MWD measured at peak exposure (between 10 and 60 minutes after dosing) from baseline to Week 16. Patients receiving treprostinil inhalation solution had a placebo-corrected median change from baseline in peak 6MWD of 21 meters at Week 16 (p=0.004) using Hodges-Lehmann estimate (Figure 3).

The treatment effect on 6MWD at Week 16 was consistent for various subgroups, including etiology of PH-ILD, disease severity, age, sex, baseline hemodynamics, and dose (Figure 4).

Time to clinical worsening in the INCREASE study was defined as the time of randomization until 1 of the following criteria were met: hospitalization due to a cardiopulmonary indication, decrease in 6MWD >15% from baseline directly related to PH-ILD at 2 consecutive visits and at least 24 hours apart, death (all causes), or lung transplantation. Treatment with treprostinil inhalation solution in patients with PH-ILD resulted in numerically fewer hospitalizations. The numbers of reported deaths were the same for both treatment groups (Table 3). Overall, treatment with treprostinil inhalation solution demonstrated a statistically significant increase in the time to first clinical worsening event (log-rank test p=0.041; Figure 5), and a 39% overall reduction in the risk of a clinical worsening event (HR=0.61 [95% CI; 0.40, 0.92]; Figure 5).

<div class="scrollingtable"><table cellpadding="3.6pt" width="100%"> <caption> <span>Table 3: Clinical Worsening Events (PH-ILD)</span> </caption> <col width="14%"/> <col width="39%"/> <col width="16%"/> <col width="16%"/> <col width="16%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Tyvaso<br/>n=163<br/>n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Placebo<br/>n=163<br/>n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">HR (95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Clinical worsening</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">37 (22.7%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">54 (33.1%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0.61 (0.40, 0.92)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="4" valign="top"> <p class="First"> <span class="Bold">First contributing event</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hospitalization due to a cardiopulmonary indication</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">18 (11.0%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">24 (14.7%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Decrease in 6MWD &gt; 15% from baseline directly related to PH-ILD</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">13 (8.0%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">26 (16.0%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Death (all causes)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.5%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4 (2.5%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Lung transplantation</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.2%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">0</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Toprule" colspan="2" valign="top"> <p class="First"> </p> </td><td align="center" class="Botrule Toprule" valign="bottom"> <p class="First"> <span class="Bold"> </span> </p> </td><td align="center" class="Botrule Toprule" valign="bottom"> <p class="First"> <span class="Bold"> </span> </p> </td><td align="center" class="Botrule Toprule" valign="bottom"> <p class="First"> <span class="Bold"> </span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" colspan="2" valign="top"></td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Tyvaso<br/>n=163<br/>n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Placebo<br/>n=163<br/>n (%)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">HR (95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" rowspan="4" valign="top"> <p class="First"> <span class="Bold">First of each event</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Hospitalization due to a cardiopulmonary indication</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">21 (12.9)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">30 (18.4%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Decrease in 6MWD &gt; 15% from baseline directly related to PH-ILD</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">16 (9.8%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">31 (19.0%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Death (all causes)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">8 (4.9%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">10 (6.1%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Lung transplantation</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2 (1.2%)</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">1 (0.6%)</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"></td> </tr> </tbody> </table></div>

YUTREPIA is supplied in a carton consisting of 1 capsule based, dry powder inhaler (referred to as “inhaler”), 28 capsules (7 foil blister cards of 4 capsules each), and 7 single-use cleaning brushes. The individual capsule well is connected by an air channel to a separate blister well containing a desiccant strip. Descriptions of YUTREPIA carton by capsule strength are provided in Table 4 below:

{ "type": "p", "children": [], "text": "YUTREPIA is supplied in a carton consisting of 1 capsule based, dry powder inhaler (referred to as “inhaler”), 28 capsules (7 foil blister cards of 4 capsules each), and 7 single-use cleaning brushes. The individual capsule well is connected by an air channel to a separate blister well containing a desiccant strip. Descriptions of YUTREPIA carton by capsule strength are provided in Table 4 below:" }

<div class="scrollingtable"><table cellpadding="3.6pt" width="75%"> <caption> <span>Table 4: YUTREPIA Carton Contents by Capsule Strength</span> </caption> <col width="23%"/> <col width="39%"/> <col width="23%"/> <thead> <tr class="First Last"> <th align="center" class="Botrule" valign="middle">Capsule Strength<br/>(mcg treprostinil)</th><th align="center" class="Botrule" valign="middle">Capsule Description</th><th align="center" class="Botrule" valign="middle">NDC Number</th> </tr> </thead> <tbody> <tr class="First"> <td align="center" class="Botrule Toprule" valign="middle"> <p class="First">26.5</p> </td><td class="Botrule Toprule" valign="middle"> <p class="First">Opaque yellow cap, clear body, imprinted with “LIQUIDIA 26.5” in black ink radially on cap</p> </td><td align="center" class="Botrule Toprule" valign="middle"> <p class="First">72964-011-01</p> </td> </tr> <tr> <td align="center" class="Botrule Toprule" valign="middle"> <p class="First">53</p> </td><td class="Botrule Toprule" valign="middle"> <p class="First">Opaque green cap, clear body, imprinted with “LIQUIDIA 53” in white ink radially on cap</p> </td><td align="center" class="Botrule Toprule" valign="middle"> <p class="First">72964-012-01</p> </td> </tr> <tr> <td align="center" class="Botrule Toprule" valign="middle"> <p class="First">79.5</p> </td><td class="Botrule Toprule" valign="middle"> <p class="First">Opaque blue cap, clear body, imprinted with “LIQUIDIA 79.5” in white ink radially on cap</p> </td><td align="center" class="Botrule Toprule" valign="middle"> <p class="First">72964-013-01</p> </td> </tr> <tr class="Last"> <td align="center" class="Toprule" valign="middle"> <p class="First">106</p> </td><td class="Toprule" valign="middle"> <p class="First">Opaque purple cap, clear body, imprinted with “LIQUIDIA 106” in white ink radially on cap</p> </td><td align="center" class="Toprule" valign="middle"> <p class="First">72964-014-01</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table cellpadding=\"3.6pt\" width=\"75%\">\n<caption>\n<span>Table 4: YUTREPIA Carton Contents by Capsule Strength</span>\n</caption>\n<col width=\"23%\"/>\n<col width=\"39%\"/>\n<col width=\"23%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Botrule\" valign=\"middle\">Capsule Strength<br/>(mcg treprostinil)</th><th align=\"center\" class=\"Botrule\" valign=\"middle\">Capsule Description</th><th align=\"center\" class=\"Botrule\" valign=\"middle\">NDC Number</th>\n</tr>\n</thead>\n<tbody>\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">26.5</p>\n</td><td class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">Opaque yellow cap, clear body, imprinted with “LIQUIDIA 26.5” in black ink radially on cap</p>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">72964-011-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">53</p>\n</td><td class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">Opaque green cap, clear body, imprinted with “LIQUIDIA 53” in white ink radially on cap</p>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">72964-012-01</p>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">79.5</p>\n</td><td class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">Opaque blue cap, clear body, imprinted with “LIQUIDIA 79.5” in white ink radially on cap</p>\n</td><td align=\"center\" class=\"Botrule Toprule\" valign=\"middle\">\n<p class=\"First\">72964-013-01</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Toprule\" valign=\"middle\">\n<p class=\"First\">106</p>\n</td><td class=\"Toprule\" valign=\"middle\">\n<p class=\"First\">Opaque purple cap, clear body, imprinted with “LIQUIDIA 106” in white ink radially on cap</p>\n</td><td align=\"center\" class=\"Toprule\" valign=\"middle\">\n<p class=\"First\">72964-014-01</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

YUTREPIA inhalation powder capsules should only be delivered using the capsule-based inhaler. The off-white plastic inhaler consists of a blue protective cap marked with YUTREPIA and a base with a mouthpiece, capsule chamber, and two blue push buttons. Discard the inhaler device after 7 days of use or 56 actuations, whichever comes first.

{ "type": "p", "children": [], "text": "YUTREPIA inhalation powder capsules should only be delivered using the capsule-based inhaler. The off-white plastic inhaler consists of a blue protective cap marked with YUTREPIA and a base with a mouthpiece, capsule chamber, and two blue push buttons. Discard the inhaler device after 7 days of use or 56 actuations, whichever comes first." }

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]." }

Capsules should remain in the blister to protect them from moisture and light, and each capsule should be removed only when ready to administer a dose.

{ "type": "p", "children": [], "text": "Capsules should remain in the blister to protect them from moisture and light, and each capsule should be removed only when ready to administer a dose." }

Keep out of the reach of children.

{ "type": "p", "children": [], "text": "Keep out of the reach of children." }

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).

{ "type": "p", "children": [], "text": "Advise the patient to read the FDA-approved patient labeling (Instructions for Use)." }

Train patients in the administration process for YUTREPIA, including dosing, inhaler preparation, administration, cleaning, and maintenance, according to the instructions for use [see Instructions for Use].

{ "type": "p", "children": [], "text": "Train patients in the administration process for YUTREPIA, including dosing, inhaler preparation, administration, cleaning, and maintenance, according to the instructions for use [see Instructions for Use]." }

To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up.

{ "type": "p", "children": [], "text": "To avoid potential interruptions in drug delivery because of equipment malfunction, patients should have access to a back-up. " }

If a scheduled dose is missed, resume therapy as soon as possible at the usual dose.

{ "type": "p", "children": [], "text": "If a scheduled dose is missed, resume therapy as soon as possible at the usual dose. " }

©Copyright 2025 Liquidia Technologies, Inc. All rights reserved.

{ "type": "p", "children": [], "text": "\n©Copyright 2025 Liquidia Technologies, Inc. All rights reserved. " }

Distributed by: Liquidia Technologies, Inc. Morrisville, NC 27560

{ "type": "p", "children": [], "text": "Distributed by: Liquidia Technologies, Inc. Morrisville, NC 27560" }

YUTREPIATM (you-TREP-ee-uh)(treprostinil)inhalation powder, for oral inhalation

{ "type": "p", "children": [], "text": "\nYUTREPIATM (you-TREP-ee-uh)(treprostinil)inhalation powder, for oral inhalation\n" }

This Instructions for Use contains information on how to inhale YUTREPIATM. Read these Instructions for Use before you start using YUTREPIA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "This Instructions for Use contains information on how to inhale YUTREPIATM. Read these Instructions for Use before you start using YUTREPIA and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Your healthcare provider should show you or your caregiver how to use YUTREPIA the right way before you use it for the first time.

{ "type": "p", "children": [], "text": "\nYour healthcare provider should show you or your caregiver how to use YUTREPIA the right way before you use it for the first time.\n" }

<div class="scrollingtable"><table class="Noautorules" width="75%"> <col width="85%"/> <tbody class="Headless"> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Important information you need to know before inhaling YUTREPIA inhalation powder:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">Do not</span> swallow YUTREPIA capsules. YUTREPIA is for inhalation only.</dd> <dt>•</dt> <dd>Use YUTREPIA as prescribed by your healthcare provider.</dd> <dt>•</dt> <dd>YUTREPIA capsules come in 4 strengths: 26.5 mcg, 53 mcg, 79.5 mcg, and 106 mcg.</dd> <dt>•</dt> <dd>If your prescribed dose is more than 106 mcg, you will need to inhale 2 YUTREPIA capsules. <span class="Bold">See Figure C</span>: Dosing Chart to help you identify the 2 capsules needed for your prescribed dose. Only use the capsule combinations in the Dosing Chart when your prescribed dose is more than 106 mcg.</dd> <dt>•</dt> <dd> <span class="Bold">The capsule must be inhaled within 5 minutes of opening the blister card or the full dose may not be administered. Read through this instruction sheet prior to the first use of this product. </span> </dd> <dt>•</dt> <dd>Always inhale each capsule 2 times to make sure you get your full dose of YUTREPIA.</dd> <dt>•</dt> <dd> <span class="Bold">Do not</span> wash the inhaler. Keep the inhaler dry.</dd> <dt>•</dt> <dd>Wash and dry your hands before using YUTREPIA.</dd> <dt>•</dt> <dd>If the contents of the capsule comes in contact with your skin or eyes, rinse the area immediately with water. </dd> <dt>•</dt> <dd>YUTREPIA capsules should remain in the blister card(s) and each capsule should be removed only when ready to deliver a dose.</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Storing YUTREPIA</span> </p> <dl> <dt>•</dt> <dd>Store YUTREPIA carton in a clean, dry place at room temperature between 68°F to 77°F (20°C to 25°C).</dd> <dt>•</dt> <dd>Leave YUTREPIA capsules in blister card to protect from moisture and light<span class="Bold">. </span> </dd> <dt>•</dt> <dd>Throw away the inhaler after 7 days of use or 56 capsules whichever comes first<span class="Bold">.</span> </dd> <dt>•</dt> <dd> <span class="Bold">Keep YUTREPIA and all medicines out of the reach of children.</span> </dd> </dl> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"75%\">\n<col width=\"85%\"/>\n<tbody class=\"Headless\">\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Important information you need to know before inhaling YUTREPIA inhalation powder:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not</span> swallow YUTREPIA capsules. YUTREPIA is for inhalation only.</dd>\n<dt>•</dt>\n<dd>Use YUTREPIA as prescribed by your healthcare provider.</dd>\n<dt>•</dt>\n<dd>YUTREPIA capsules come in 4 strengths: 26.5 mcg, 53 mcg, 79.5 mcg, and 106 mcg.</dd>\n<dt>•</dt>\n<dd>If your prescribed dose is more than 106 mcg, you will need to inhale 2 YUTREPIA capsules. <span class=\"Bold\">See Figure C</span>: Dosing Chart to help you identify the 2 capsules needed for your prescribed dose. Only use the capsule combinations in the Dosing Chart when your prescribed dose is more than 106 mcg.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">The capsule must be inhaled within 5 minutes of opening the blister card or the full dose may not be administered. Read through this instruction sheet prior to the first use of this product. </span>\n</dd>\n<dt>•</dt>\n<dd>Always inhale each capsule 2 times to make sure you get your full dose of YUTREPIA.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Do not</span> wash the inhaler. Keep the inhaler dry.</dd>\n<dt>•</dt>\n<dd>Wash and dry your hands before using YUTREPIA.</dd>\n<dt>•</dt>\n<dd>If the contents of the capsule comes in contact with your skin or eyes, rinse the area immediately with water. </dd>\n<dt>•</dt>\n<dd>YUTREPIA capsules should remain in the blister card(s) and each capsule should be removed only when ready to deliver a dose.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Storing YUTREPIA</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>Store YUTREPIA carton in a clean, dry place at room temperature between 68°F to 77°F (20°C to 25°C).</dd>\n<dt>•</dt>\n<dd>Leave YUTREPIA capsules in blister card to protect from moisture and light<span class=\"Bold\">. </span>\n</dd>\n<dt>•</dt>\n<dd>Throw away the inhaler after 7 days of use or 56 capsules whichever comes first<span class=\"Bold\">.</span>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">Keep YUTREPIA and all medicines out of the reach of children.</span>\n</dd>\n</dl>\n</td>\n</tr>\n</tbody>\n</table></div>" }

<div class="scrollingtable"><table width="75%"> <col width="40%"/> <col width="45%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Text</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Illustration</span> </p> </td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Get to know YUTREPIA</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">The YUTREPIA carton contains (See Figure A):</p> <dl> <dt>•</dt> <dd>1 dry powder inhaler (called “inhaler” in these instructions)</dd> <dt>•</dt> <dd>7 Foil blister cards of YUTREPIA capsules (called “capsules” in these instructions) containing 4 capsules each, in one of 4 available strengths</dd> <dt>•</dt> <dd>7 Cleaning brushes (1 for each day)</dd> <dt>•</dt> <dd>1 Desiccant tab within each blister strip to keep the capsule dry and prevent moisture. Throw away the blister strip and the desiccant tab after removing the capsule.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-249888560"></a><img alt="Figure A - IFU" src="/dailymed/image.cfm?name=image-07.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Preparing to use YUTREPIA</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">The capsule must be inhaled within 5 minutes of opening the blister card. Ensure all supplies are gathered and you are familiar with the use of the product prior to opening the card. <br/> <br/> </span> </p> <p> <span class="Bold">STEP 1. Gather your supplies.</span> </p> <dl> <dt>a.</dt> <dd>Place your YUTREPIA carton on a clean, dry surface.</dd> <dt>b.</dt> <dd>Remove the inhaler and foil blister cards from the carton <span class="Bold">(See Figure B)</span>.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id1522194836"></a><img alt="Figure B - IFU" src="/dailymed/image.cfm?name=image-08.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 2. Select the capsule(s) for your dose.</span> </p> <p>Use the Dosing Chart <span class="Bold">(See</span><span class="Bold"> Figure C)</span> to help you identify the capsule(s) needed for your prescribed dose.</p> <dl> <dt>•</dt> <dd>If your prescribed dose is more than 106 mcg, you will need to inhale 2 capsules per the Dosing Chart <span class="Bold">(see Figure C)</span>.</dd> <dt>•</dt> <dd>Only load and inhale 1 capsule at a time.</dd> <dt>•</dt> <dd>All capsules in a carton are the same strength. If your prescribed dose requires 2 capsules of different strengths, you will need to select your capsules from 2 separate cartons.</dd> </dl> <p> <span class="Bold">IMPORTANT: </span>For doses requiring 2 capsules, only use the capsule combinations presented in the Dosing Chart <span class="Bold">(See Figure C)</span>. The order for inhaling 2 capsules does not matter, regardless of capsule strength.</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-1631008583"></a><img alt="Figure C - IFU" src="/dailymed/image.cfm?name=image-09.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 3. Check the inhaler and blister card(s).</span> </p> <dl> <dt>a.</dt> <dd>Look at the inhaler and blister card(s) to make sure they are not damaged <span class="Bold">(See Figure D)</span>.<br/> <span class="Bold">Do not </span>use the inhaler or capsules if they are damaged.</dd> <dt>b.</dt> <dd>Look at the expiration date on the blister cards to make sure it has not passed <span class="Bold">(See</span><span class="Bold"> Figure E)</span>.<br/> <span class="Bold">Do not </span>use the capsules if the expiration date has passed.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-1979369852"></a><img alt="Figure D - IFU" src="/dailymed/image.cfm?name=image-10.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id81199609"></a><img alt="Figure E - IFU" src="/dailymed/image.cfm?name=image-11.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Loading YUTREPIA</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 4. Open the inhaler.</span> </p> <dl> <dt>a.</dt> <dd>Pull the cover straight off the inhaler <span class="Bold">(See Figure F)</span>.</dd> <dt>b.</dt> <dd>Rotate the mouthpiece in the direction of the arrow (counter-clockwise) to open the inhaler and expose the capsule chamber <span class="Bold">(See Figure G)</span>.<br/>If the mouthpiece separates from the base of the inhaler, gently reattach the 2 pieces and continue to follow the instructions.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id1173217104"></a><img alt="Figure F - IFU" src="/dailymed/image.cfm?name=image-12.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id-1938826607"></a><img alt="Figure G - IFU" src="/dailymed/image.cfm?name=image-13.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 5. Remove the capsule from the blister strip.</span> </p> <dl> <dt>a.</dt> <dd>Separate 1 blister strip by tearing at the pre-cut lines <span class="Bold">(See</span><span class="Bold"> Figure H)</span>.<br/> <span class="Bold">Do not</span> remove a capsule from the blister strip until you are ready to deliver your dose.</dd> <dt>b.</dt> <dd>Peel the foil away from the blister strip, remove the capsule <span class="Bold">(See</span><span class="Bold"> Figure I)</span>.<br/> <span class="Bold">Do not</span> swallow the capsule.<br/> <span class="Bold">Do not</span> push the capsule through the foil.<br/> <span class="Bold">Do not</span> remove the desiccant tab.<br/> <span class="Bold">Capsule</span> must be used <span class="Bold">within 5 minutes</span> of opening the blister card.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-1831508194"></a><img alt="Figure H - IFU" src="/dailymed/image.cfm?name=image-14.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id1071696286"></a><img alt="Figure i - IFU" src="/dailymed/image.cfm?name=image-15.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 6. Secure the capsule in the inhaler.</span> </p> <dl> <dt>a.</dt> <dd>Hold the inhaler in an upright position.</dd> <dt>b.</dt> <dd>Place the capsule in the capsule chamber in the base of the inhaler <span class="Bold">(See</span><span class="Bold"> Figure J)</span>. Only load 1 capsule.<br/> <span class="Bold">Do not</span> place a capsule in the mouthpiece.<br/> <span class="Bold">Do not</span> swallow capsules.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id769504993"></a><img alt="Figure J - IFU" src="/dailymed/image.cfm?name=image-16.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 7. Puncture the capsule.</span> </p> <dl> <dt>a.</dt> <dd>Put one finger on top of the capsule to hold it down <span class="Bold">(See Figure</span><span class="Bold"> K)</span>.</dd> <dt>b.</dt> <dd>While still holding down the capsule, firmly press both puncture buttons all the way in with your other hand <span class="Bold">(See</span><span class="Bold"> Figure L).<br/> </span>Then let go of (release) the puncture buttons.<br/>This will puncture the capsule. You only need to press the puncture buttons 1 time.</dd> <dt>c.</dt> <dd>Hold the base of the inhaler and<br/>rotate the mouthpiece to close it.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id2008095826"></a><img alt="Figure K - IFU" src="/dailymed/image.cfm?name=image-17.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id971644441"></a><img alt="Figure L - IFU" src="/dailymed/image.cfm?name=image-18.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Inhaling YUTREPIA</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 8. Position the inhaler.</span> </p> <dl> <dt>a.</dt> <dd>Hold the inhaler upright and away from your mouth. <span class="Bold">(See Figure M)</span>.<br/> <span class="Bold">Do not</span> hold the inhaler by the puncture buttons.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-1700699378"></a><img alt="Figure M - IFU" src="/dailymed/image.cfm?name=image-19.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 9. Breathe out (exhale).</span> </p> <dl> <dt>a.</dt> <dd>Breathe out fully and away from the inhaler <span class="Bold">(See Figure N)</span>.<br/> <span class="Bold">Do not</span> exhale into the mouthpiece.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id647180661"></a><img alt="Figure N - IFU" src="/dailymed/image.cfm?name=image-20.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 10. Breathe in deeply (inhale)</span> </p> <dl> <dt>a.</dt> <dd>Close your lips around the mouthpiece <span class="Bold">(See Figure O)</span>.</dd> <dt>b.</dt> <dd>Tilt your head back slightly <span class="Bold">(See</span><span class="Bold"> Figure O)</span>.</dd> <dt>c.</dt> <dd>Take a comfortable deep breath in (inhale) until your lungs feel full <span class="Bold">(See Figure O)</span>.<br/>As you inhale, you will hear or feel a whirring noise as the capsule spins and releases medicine.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id1426691679"></a><img alt="Figure O - IFU" src="/dailymed/image.cfm?name=image-21.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 11. Hold breath, then breathe out (exhale).</span> </p> <dl> <dt>a.</dt> <dd>Take the inhaler out of your mouth and hold your breath for 5 seconds or as long as you comfortably can <span class="Bold">(See Figure P)</span>.</dd> <dt>b.</dt> <dd>Then breathe out normally.<br/> <br/> </dd> </dl> <p> <span class="Bold">IMPORTANT: </span>If you cough when inhaling, repeat STEP 8 through11.</p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-838308560"></a><img alt="Figure P - IFU" src="/dailymed/image.cfm?name=image-22.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 12. Inhale again.</span> </p> <dl> <dt>a.</dt> <dd>To make sure the capsule is completely emptied of medicine, repeat STEP 8 through11 <span class="Bold">(See Figure Q)</span>.<br/>Always inhale each capsule 2 times to make sure you get your full dose.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id624735993"></a><img alt="Figure Q - IFU" src="/dailymed/image.cfm?name=image-23.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Removing and disposing of the capsule</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 13. Open the inhaler.</span> </p> <dl> <dt>a.</dt> <dd>Rotate the mouthpiece in the direction of the arrow (counter-clockwise) to open the inhaler and expose the capsule chamber <span class="Bold">(See</span><span class="Bold"> Figure R)</span>.</dd> <dt>b.</dt> <dd>Remove the used (empty) capsule and throw away (dispose of) into household trash <span class="Bold">(See Figure S)</span>.</dd> <dt>c.</dt> <dd>See box below if you need to use more than 1 capsule to complete your prescribed dose.</dd> <dt>d.</dt> <dd>Continue to Step 14 if you have completed your prescribed dose.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id382986315"></a><img alt="Figure R - IFU" src="/dailymed/image.cfm?name=image-24.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id-37980083"></a><img alt="Figure S - IFU" src="/dailymed/image.cfm?name=image-25.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" colspan="2" valign="top"><a name="id1164437088"></a><img alt="When dosing with more than one capsule..." src="/dailymed/image.cfm?name=image-26.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Closing and storing the inhaler</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">STEP 14. Close the inhaler.</span> </p> <dl> <dt>a.</dt> <dd>Hold the base of the inhaler and rotate the mouthpiece to close it <span class="Bold">(See Figure T).</span> </dd> <dt>b.</dt> <dd>Put the cover on the inhaler <span class="Bold">(See</span><span class="Bold"> Figure U)</span>.</dd> <dt>c.</dt> <dd>Store the inhaler in a clean, dry place at room temperature.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id-1167627174"></a><img alt="Figure T - IFU" src="/dailymed/image.cfm?name=image-27.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id498464218"></a><img alt="Figure U - IFU" src="/dailymed/image.cfm?name=image-28.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Cleaning the inhaler (at end of each day)</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First"> <span class="Bold">Clean the outside and inside of the inhaler after your last dose of the day.</span> </p> <dl> <dt>a.</dt> <dd>Wipe the mouthpiece with a dry paper towel, tissue, or clean dry cloth <span class="Bold">(See Figure V)</span>.</dd> <dt>b.</dt> <dd>Use the cleaning brush provided to clean the capsule chamber in order to remove visible powder buildup <span class="Bold">(See</span><span class="Bold"> Figure W)</span>.<br/> <span class="Bold">NOTE: </span>Throw away the brush after cleaning. Use only 1 brush each day.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id1144784693"></a><img alt="Figure V - IFU" src="/dailymed/image.cfm?name=image-29.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/><a name="id1057275343"></a><img alt="Figure W - IFU" src="/dailymed/image.cfm?name=image-30.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> <tr> <td class="Botrule Lrule" valign="top"> <p class="First"> <span class="Bold">Disposing of the inhaler</span> </p> </td><td class="Botrule Rrule Toprule" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Throw away (dispose of) the inhaler into household trash after 7 days of use.</span> </p> <dl> <dt>a.</dt> <dd>The inhaler is reusable and will last for 7 days (1 week) or 56 capsules, whichever comes first. <br/> <span class="Bold">(See</span><span class="Bold"> Figure X)</span>.</dd> </dl> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><a name="id1232968708"></a><img alt="Figure X - IFU" src="/dailymed/image.cfm?name=image-31.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468"/></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"75%\">\n<col width=\"40%\"/>\n<col width=\"45%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Text</span>\n</p>\n</td><td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Illustration</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Get to know YUTREPIA</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">The YUTREPIA carton contains (See Figure A):</p>\n<dl>\n<dt>•</dt>\n<dd>1 dry powder inhaler (called “inhaler” in these instructions)</dd>\n<dt>•</dt>\n<dd>7 Foil blister cards of YUTREPIA capsules (called “capsules” in these instructions) containing 4 capsules each, in one of 4 available strengths</dd>\n<dt>•</dt>\n<dd>7 Cleaning brushes (1 for each day)</dd>\n<dt>•</dt>\n<dd>1 Desiccant tab within each blister strip to keep the capsule dry and prevent moisture. Throw away the blister strip and the desiccant tab after removing the capsule.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-249888560\"></a><img alt=\"Figure A - IFU\" src=\"/dailymed/image.cfm?name=image-07.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Preparing to use YUTREPIA</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">The capsule must be inhaled within 5 minutes of opening the blister card. Ensure all supplies are gathered and you are familiar with the use of the product prior to opening the card. <br/>\n<br/>\n</span>\n</p>\n<p>\n<span class=\"Bold\">STEP 1. Gather your supplies.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Place your YUTREPIA carton on a clean, dry surface.</dd>\n<dt>b.</dt>\n<dd>Remove the inhaler and foil blister cards from the carton <span class=\"Bold\">(See Figure B)</span>.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id1522194836\"></a><img alt=\"Figure B - IFU\" src=\"/dailymed/image.cfm?name=image-08.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 2. Select the capsule(s) for your dose.</span>\n</p>\n<p>Use the Dosing Chart <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure C)</span> to help you identify the capsule(s) needed for your prescribed dose.</p>\n<dl>\n<dt>•</dt>\n<dd>If your prescribed dose is more than 106 mcg, you will need to inhale 2 capsules per the Dosing Chart <span class=\"Bold\">(see Figure C)</span>.</dd>\n<dt>•</dt>\n<dd>Only load and inhale 1 capsule at a time.</dd>\n<dt>•</dt>\n<dd>All capsules in a carton are the same strength. If your prescribed dose requires 2 capsules of different strengths, you will need to select your capsules from 2 separate cartons.</dd>\n</dl>\n<p>\n<span class=\"Bold\">IMPORTANT: </span>For doses requiring 2 capsules, only use the capsule combinations presented in the Dosing Chart <span class=\"Bold\">(See Figure C)</span>. The order for inhaling 2 capsules does not matter, regardless of capsule strength.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-1631008583\"></a><img alt=\"Figure C - IFU\" src=\"/dailymed/image.cfm?name=image-09.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 3. Check the inhaler and blister card(s).</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Look at the inhaler and blister card(s) to make sure they are not damaged <span class=\"Bold\">(See Figure D)</span>.<br/>\n<span class=\"Bold\">Do not </span>use the inhaler or capsules if they are damaged.</dd>\n<dt>b.</dt>\n<dd>Look at the expiration date on the blister cards to make sure it has not passed <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure E)</span>.<br/>\n<span class=\"Bold\">Do not </span>use the capsules if the expiration date has passed.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-1979369852\"></a><img alt=\"Figure D - IFU\" src=\"/dailymed/image.cfm?name=image-10.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id81199609\"></a><img alt=\"Figure E - IFU\" src=\"/dailymed/image.cfm?name=image-11.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Loading YUTREPIA</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 4. Open the inhaler.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Pull the cover straight off the inhaler <span class=\"Bold\">(See Figure F)</span>.</dd>\n<dt>b.</dt>\n<dd>Rotate the mouthpiece in the direction of the arrow (counter-clockwise) to open the inhaler and expose the capsule chamber <span class=\"Bold\">(See Figure G)</span>.<br/>If the mouthpiece separates from the base of the inhaler, gently reattach the 2 pieces and continue to follow the instructions.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id1173217104\"></a><img alt=\"Figure F - IFU\" src=\"/dailymed/image.cfm?name=image-12.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id-1938826607\"></a><img alt=\"Figure G - IFU\" src=\"/dailymed/image.cfm?name=image-13.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 5. Remove the capsule from the blister strip.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Separate 1 blister strip by tearing at the pre-cut lines <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure H)</span>.<br/>\n<span class=\"Bold\">Do not</span> remove a capsule from the blister strip until you are ready to deliver your dose.</dd>\n<dt>b.</dt>\n<dd>Peel the foil away from the blister strip, remove the capsule <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure I)</span>.<br/>\n<span class=\"Bold\">Do not</span> swallow the capsule.<br/>\n<span class=\"Bold\">Do not</span> push the capsule through the foil.<br/>\n<span class=\"Bold\">Do not</span> remove the desiccant tab.<br/>\n<span class=\"Bold\">Capsule</span> must be used <span class=\"Bold\">within 5 minutes</span> of opening the blister card.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-1831508194\"></a><img alt=\"Figure H - IFU\" src=\"/dailymed/image.cfm?name=image-14.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id1071696286\"></a><img alt=\"Figure i - IFU\" src=\"/dailymed/image.cfm?name=image-15.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 6. Secure the capsule in the inhaler.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Hold the inhaler in an upright position.</dd>\n<dt>b.</dt>\n<dd>Place the capsule in the capsule chamber in the base of the inhaler <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure J)</span>. Only load 1 capsule.<br/>\n<span class=\"Bold\">Do not</span> place a capsule in the mouthpiece.<br/>\n<span class=\"Bold\">Do not</span> swallow capsules.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id769504993\"></a><img alt=\"Figure J - IFU\" src=\"/dailymed/image.cfm?name=image-16.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 7. Puncture the capsule.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Put one finger on top of the capsule to hold it down <span class=\"Bold\">(See Figure</span><span class=\"Bold\"> K)</span>.</dd>\n<dt>b.</dt>\n<dd>While still holding down the capsule, firmly press both puncture buttons all the way in with your other hand <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure L).<br/>\n</span>Then let go of (release) the puncture buttons.<br/>This will puncture the capsule. You only need to press the puncture buttons 1 time.</dd>\n<dt>c.</dt>\n<dd>Hold the base of the inhaler and<br/>rotate the mouthpiece to close it.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id2008095826\"></a><img alt=\"Figure K - IFU\" src=\"/dailymed/image.cfm?name=image-17.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id971644441\"></a><img alt=\"Figure L - IFU\" src=\"/dailymed/image.cfm?name=image-18.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Inhaling YUTREPIA</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 8. Position the inhaler.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Hold the inhaler upright and away from your mouth. <span class=\"Bold\">(See Figure M)</span>.<br/>\n<span class=\"Bold\">Do not</span> hold the inhaler by the puncture buttons.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-1700699378\"></a><img alt=\"Figure M - IFU\" src=\"/dailymed/image.cfm?name=image-19.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 9. Breathe out (exhale).</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Breathe out fully and away from the inhaler <span class=\"Bold\">(See Figure N)</span>.<br/>\n<span class=\"Bold\">Do not</span> exhale into the mouthpiece.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id647180661\"></a><img alt=\"Figure N - IFU\" src=\"/dailymed/image.cfm?name=image-20.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 10. Breathe in deeply (inhale)</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Close your lips around the mouthpiece <span class=\"Bold\">(See Figure O)</span>.</dd>\n<dt>b.</dt>\n<dd>Tilt your head back slightly <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure O)</span>.</dd>\n<dt>c.</dt>\n<dd>Take a comfortable deep breath in (inhale) until your lungs feel full <span class=\"Bold\">(See Figure O)</span>.<br/>As you inhale, you will hear or feel a whirring noise as the capsule spins and releases medicine.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id1426691679\"></a><img alt=\"Figure O - IFU\" src=\"/dailymed/image.cfm?name=image-21.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 11. Hold breath, then breathe out (exhale).</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Take the inhaler out of your mouth and hold your breath for 5 seconds or as long as you comfortably can <span class=\"Bold\">(See Figure P)</span>.</dd>\n<dt>b.</dt>\n<dd>Then breathe out normally.<br/>\n<br/>\n</dd>\n</dl>\n<p>\n<span class=\"Bold\">IMPORTANT: </span>If you cough when inhaling, repeat STEP 8 through11.</p>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-838308560\"></a><img alt=\"Figure P - IFU\" src=\"/dailymed/image.cfm?name=image-22.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 12. Inhale again.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>To make sure the capsule is completely emptied of medicine, repeat STEP 8 through11 <span class=\"Bold\">(See Figure Q)</span>.<br/>Always inhale each capsule 2 times to make sure you get your full dose.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id624735993\"></a><img alt=\"Figure Q - IFU\" src=\"/dailymed/image.cfm?name=image-23.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Removing and disposing of the capsule</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 13. Open the inhaler.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Rotate the mouthpiece in the direction of the arrow (counter-clockwise) to open the inhaler and expose the capsule chamber <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure R)</span>.</dd>\n<dt>b.</dt>\n<dd>Remove the used (empty) capsule and throw away (dispose of) into household trash <span class=\"Bold\">(See Figure S)</span>.</dd>\n<dt>c.</dt>\n<dd>See box below if you need to use more than 1 capsule to complete your prescribed dose.</dd>\n<dt>d.</dt>\n<dd>Continue to Step 14 if you have completed your prescribed dose.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id382986315\"></a><img alt=\"Figure R - IFU\" src=\"/dailymed/image.cfm?name=image-24.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id-37980083\"></a><img alt=\"Figure S - IFU\" src=\"/dailymed/image.cfm?name=image-25.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule\" colspan=\"2\" valign=\"top\"><a name=\"id1164437088\"></a><img alt=\"When dosing with more than one capsule...\" src=\"/dailymed/image.cfm?name=image-26.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Closing and storing the inhaler</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">STEP 14. Close the inhaler.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Hold the base of the inhaler and rotate the mouthpiece to close it <span class=\"Bold\">(See Figure T).</span>\n</dd>\n<dt>b.</dt>\n<dd>Put the cover on the inhaler <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure U)</span>.</dd>\n<dt>c.</dt>\n<dd>Store the inhaler in a clean, dry place at room temperature.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id-1167627174\"></a><img alt=\"Figure T - IFU\" src=\"/dailymed/image.cfm?name=image-27.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id498464218\"></a><img alt=\"Figure U - IFU\" src=\"/dailymed/image.cfm?name=image-28.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Cleaning the inhaler (at end of each day)</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Clean the outside and inside of the inhaler after your last dose of the day.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>Wipe the mouthpiece with a dry paper towel, tissue, or clean dry cloth <span class=\"Bold\">(See Figure V)</span>.</dd>\n<dt>b.</dt>\n<dd>Use the cleaning brush provided to clean the capsule chamber in order to remove visible powder buildup <span class=\"Bold\">(See</span><span class=\"Bold\"> Figure W)</span>.<br/>\n<span class=\"Bold\">NOTE: </span>Throw away the brush after cleaning. Use only 1 brush each day.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id1144784693\"></a><img alt=\"Figure V - IFU\" src=\"/dailymed/image.cfm?name=image-29.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/><a name=\"id1057275343\"></a><img alt=\"Figure W - IFU\" src=\"/dailymed/image.cfm?name=image-30.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Disposing of the inhaler</span>\n</p>\n</td><td class=\"Botrule Rrule Toprule\" valign=\"top\"></td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule Toprule\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Throw away (dispose of) the inhaler into household trash after 7 days of use.</span>\n</p>\n<dl>\n<dt>a.</dt>\n<dd>The inhaler is reusable and will last for 7 days (1 week) or 56 capsules, whichever comes first. <br/>\n<span class=\"Bold\">(See</span><span class=\"Bold\"> Figure X)</span>.</dd>\n</dl>\n</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><a name=\"id1232968708\"></a><img alt=\"Figure X - IFU\" src=\"/dailymed/image.cfm?name=image-31.jpg&amp;setid=e8f6d534-115c-440e-bdbb-b443a29bb468\"/></td>\n</tr>\n</tbody>\n</table></div>" }

©Copyright 2025 Liquidia Technologies, Inc. All rights reserved. Distributed by: Liquidia Technologies, Inc. Morrisville, NC 27560For more information call 1-888-393-LQDA (5732) or go to www.YUTREPIA.com

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This Instructions for Use has been approved by the U.S. Food and Drug Administration

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Issued: June 2025

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{ "type": "", "children": [], "text": "" }

NDC 72964-011-01 Rx Only

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26.5 mcg per capsule

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Yutrepia™ (treprostinil) inhalation powder

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For oral inhalation only DO NOT SWALLOW YUTREPIA CAPSULES

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Contents:

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Liquidia™

{ "type": "p", "children": [], "text": "\nLiquidia™\n" }

NDC 72964-011-01 Rx Only

{ "type": "p", "children": [], "text": "NDC 72964-011-01\nRx Only\n" }

26.5 mcg per capsule

{ "type": "p", "children": [], "text": "\n26.5 mcg\nper capsule" }

Yutrepia™ (treprostinil) inhalation powder

{ "type": "p", "children": [], "text": "\nYutrepia™\n(treprostinil) inhalation powder" }

Read Instructions for Use before each use. Recommended Dosage: See prescribing information. Do not remove capsules from blister cards until immediately before use.Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to86°F (15°C to 30°C) [see USP Controlled Room Temperature].Keep this and all drugs out of the reach of children.

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Distributed by:Liquidia Technologies Inc.Morrisville, NC 27560

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Liquidia™

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{ "type": "", "children": [], "text": "" }

NDC 72964-012-01 Rx Only

{ "type": "p", "children": [], "text": "NDC 72964-012-01\nRx Only\n" }

53 mcg per capsule

{ "type": "p", "children": [], "text": "\n53 mcg\nper capsule" }

Yutrepia™ (treprostinil) inhalation powder

{ "type": "p", "children": [], "text": "\nYutrepia™\n(treprostinil) inhalation powder" }

For oral inhalation only DO NOT SWALLOW YUTREPIA CAPSULES

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Contents:

{ "type": "p", "children": [], "text": "Contents:" }

{ "type": "", "children": [], "text": "" }

Liquidia™

{ "type": "p", "children": [], "text": "\nLiquidia™\n" }

NDC 72964-012-01 Rx Only

{ "type": "p", "children": [], "text": "NDC 72964-012-01\nRx Only\n" }

26.5 mcg per capsule

{ "type": "p", "children": [], "text": "\n26.5 mcg\nper capsule" }

Yutrepia™ (treprostinil) inhalation powder

{ "type": "p", "children": [], "text": "\nYutrepia™\n(treprostinil) inhalation powder" }

Read Instructions for Use before each use. Recommended Dosage: See prescribing information. Do not remove capsules from blister cards until immediately before use.Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to86°F (15°C to 30°C) [see USP Controlled Room Temperature].Keep this and all drugs out of the reach of children.

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Distributed by:Liquidia Technologies Inc.Morrisville, NC 27560

{ "type": "p", "children": [], "text": "Distributed by:Liquidia Technologies Inc.Morrisville, NC 27560" }

Liquidia™

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{ "type": "", "children": [], "text": "" }

NDC 72964-013-01

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Rx Only

{ "type": "p", "children": [], "text": "\nRx Only\n" }

79.5 mcg per capsule

{ "type": "p", "children": [], "text": "\n79.5 mcg\nper capsule" }

Yutrepia™ (treprostinil) inhalation powder

{ "type": "p", "children": [], "text": "\nYutrepia™\n(treprostinil) inhalation powder" }

For oral inhalation only DO NOT SWALLOW YUTREPIA CAPSULES

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Contents:

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Liquidia™

{ "type": "p", "children": [], "text": "\nLiquidia™\n" }

NDC 72964-013-01 Rx Only

{ "type": "p", "children": [], "text": "NDC 72964-013-01\nRx Only\n" }

79.5 mcg per capsule

{ "type": "p", "children": [], "text": "\n79.5 mcg\nper capsule" }

Yutrepia™ (treprostinil) inhalation powder

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Read Instructions for Use before each use. Recommended Dosage: See prescribing information. Do not remove capsules from blister cards until immediately before use.Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to86°F (15°C to 30°C) [see USP Controlled Room Temperature].Keep this and all drugs out of the reach of children.

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Distributed by:Liquidia Technologies Inc.Morrisville, NC 27560

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Liquidia™

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NDC 72964-014-01 Rx Only

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106 mcg per capsule

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Yutrepia™ (treprostinil) inhalation powder

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For oral inhalation only DO NOT SWALLOW YUTREPIA CAPSULES

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Contents:

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Liquidia™

{ "type": "p", "children": [], "text": "\nLiquidia™\n" }

NDC 72964-014-01 Rx Only

{ "type": "p", "children": [], "text": "NDC 72964-014-01\nRx Only\n" }

106 mcg per capsule

{ "type": "p", "children": [], "text": "\n106 mcg\nper capsule" }

Yutrepia™ (treprostinil) inhalation powder

{ "type": "p", "children": [], "text": "\nYutrepia™\n(treprostinil) inhalation powder" }

Read Instructions for Use before each use. Recommended Dosage: See prescribing information. Do not remove capsules from blister cards until immediately before use.Store at 68°F to 77°F (20°C to 25°C); excursions permitted to 59°F to86°F (15°C to 30°C) [see USP Controlled Room Temperature].Keep this and all drugs out of the reach of children.

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Distributed by:Liquidia Technologies Inc.Morrisville, NC 27560

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Liquidia™

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Orenitram is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity.

The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%).

Take Orenitram with food. Swallow Orenitram tablets whole; do not crush, split, or chew.

The recommended starting dose of Orenitram is 0.125 mg three times daily (TID) with food, taken approximately 8 hours apart or 0.25 mg twice daily (BID) with food, taken approximately 12 hours apart.

Titrate by 0.125 mg TID or 0.25 or 0.5 mg BID not more frequently than every 3 to 4 days. Increase the dose to the highest tolerated dose. The recommended maximum daily dose is 120 mg.

If dose increments are not tolerated, consider titrating slower. If intolerable pharmacologic effects occur, decrease the dose in increments of 0.125 mg TID or 0.25 mg BID. Avoid abrupt discontinuation [see Warnings and Precautions (5.1)].

Decrease the dose of Remodulin while simultaneously increasing the dose of Orenitram. The dose of Remodulin can be reduced up to 30 ng/kg/min per day and the dose of Orenitram simultaneously increased up to 6 mg per day (2 mg TID) if tolerated. The following equation can be used to estimate a target total daily dose of Orenitram in mg using a patient's dose of intravenous (IV)/subcutaneous (SC) treprostinil (in ng/kg/min) and weight (in kg).

Orenitram total daily dose (mg) = 0.0072 × Remodulin dose (ng/kg/min) × weight (kg)

In patients with mild hepatic impairment (Child Pugh Class A) start at 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days. Avoid use of Orenitram in patients with moderate hepatic impairment (Child Pugh Class B). Orenitram is contraindicated in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure [see Contraindications (4), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

When co-administered with strong CYP2C8 inhibitors (e.g., gemfibrozil) the initial dose is 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days.

If a dose of medication is missed, the patient should take the missed dose as soon as possible, with food. If a patient misses two or more doses, restart at a lower dose and re-titrate.

In the event of a planned short-term treatment interruption for patients unable to take oral medications, consider a temporary infusion of subcutaneous or intravenous treprostinil. To calculate the total daily dose (mg) of treprostinil for the parenteral route use the following equation:

<div class="scrollingtable"><table class="Noautorules" width="70%"> <col align="right" valign="top" width="30%"/> <col align="left" valign="top" width="70%"/> <tbody class="Headless"> <tr> <td align="right"><span class="Bold">Remodulin (ng/kg/min) = </span></td><td align="left"><span class="Bold Underline">139 × Orenitram total daily dose (mg)</span></td> </tr> <tr> <td align="right"></td><td align="left"><span class="Bold">                      weight (kg)</span></td> </tr> </tbody> </table></div>

When discontinuing Orenitram, reduce the dose in steps of 0.5 to 1 mg per day [see Warnings and Precautions (5.1)].

Orenitram (treprostinil) extended-release tablets are available in the following five strengths:

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Severe hepatic impairment (Child Pugh Class C) [see Use In Specific Populations (8.6) and Clinical Pharmacology (12.3)].

{ "type": "p", "children": [], "text": "Severe hepatic impairment (Child Pugh Class C) [see Use In Specific Populations (8.6) and Clinical Pharmacology (12.3)]." }

Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms.

The tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In a 12-week, placebo-controlled, monotherapy study (Study 1; WHO Group 1; functional class II-III), and an event-driven, placebo-controlled, combination therapy study (Study 4; WHO Group 1; functional class I-III), the most commonly reported adverse reactions that occurred in patients receiving Orenitram included: headache, diarrhea, nausea, and flushing.

Orenitram patients in Study 1 (N=151) had access to 0.25 mg tablets at randomization. Approximately 91% of such patients in Study 1 experienced an adverse reaction, but only 4% discontinued therapy for an adverse reaction (compared to 3% receiving placebo). Study 4 enrolled a total of 690 patients, 346 received Orenitram and 344 received placebo. Overall, 19% of patients treated with Orenitram discontinued treatment in Study 4 due to an adverse event (compared to 4% of patients receiving placebo). The exposure to Orenitram in Study 4 was up to 5.1 years with a median duration of exposure of 1.2 years. Table 1 summarizes adverse events with rates at least 5% higher on Orenitram therapy than on placebo that were reported in either Study 1 or 4.

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 1: Adverse Events with Rates at Least 5% Higher on Orenitram Therapy than on Placebo in Either Study 1 or Study 4</span> </caption> <col align="left" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <col align="center" valign="top" width="20%"/> <thead> <tr class="Botrule First"> <th align="left" class="Lrule Rrule" rowspan="2" valign="middle">Reaction</th><th align="center" class="Rrule" colspan="2">Study 1<br/>N=228<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a></th><th align="center" class="Rrule" colspan="2">Study 4<br/>N=690</th> </tr> <tr class="Last"> <th align="center" class="Rrule">Orenitram<br/>n=151</th><th align="center" class="Rrule">Placebo<br/>n=77</th><th align="center" class="Rrule">Orenitram<br/>n=346</th><th align="center" class="Rrule">Placebo<br/>n=344</th> </tr> </thead> <tfoot> <tr> <td align="left" colspan="5"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>Includes all subjects in the Primary Analysis Population</dd> </dl> </td> </tr> </tfoot> <tbody> <tr class="First"> <td align="left" class="Lrule Rrule">Headache</td><td align="center" class="Rrule">63%</td><td align="center" class="Rrule">19%</td><td align="center" class="Rrule">75%</td><td align="center" class="Rrule">35%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule Toprule">Diarrhea</td><td align="center" class="Rrule Toprule">30%</td><td align="center" class="Rrule Toprule">16%</td><td align="center" class="Rrule Toprule">69%</td><td align="center" class="Rrule Toprule">29%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Nausea</td><td align="center" class="Rrule">30%</td><td align="center" class="Rrule">18%</td><td align="center" class="Rrule">40%</td><td align="center" class="Rrule">23%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Vomiting</td><td align="center" class="Rrule">17%</td><td align="center" class="Rrule">16%</td><td align="center" class="Rrule">36%</td><td align="center" class="Rrule">10%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Flushing</td><td align="center" class="Rrule">15%</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">45%</td><td align="center" class="Rrule">8%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Pain in jaw</td><td align="center" class="Rrule">11%</td><td align="center" class="Rrule">4%</td><td align="center" class="Rrule">18%</td><td align="center" class="Rrule">3%</td> </tr> <tr> <td align="left" class="Lrule Rrule">Pain in extremity</td><td align="center" class="Rrule">14%</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">18%</td><td align="center" class="Rrule">9%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule Toprule">Hypokalemia</td><td align="center" class="Rrule Toprule">9%</td><td align="center" class="Rrule Toprule">3%</td><td align="center" class="Rrule Toprule">4%</td><td align="center" class="Rrule Toprule">3%</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule">Abdominal discomfort</td><td align="center" class="Rrule">6%</td><td align="center" class="Rrule">0%</td><td align="center" class="Rrule">8%</td><td align="center" class="Rrule">4%</td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule">Upper abdominal pain</td><td align="center" class="Rrule">5%</td><td align="center" class="Rrule">3%</td><td align="center" class="Rrule">12%</td><td align="center" class="Rrule">5%</td> </tr> </tbody> </table></div>

Orenitram was studied in a long-term, open-label, extension study in which 824 patients were dosed for a mean duration of approximately 2 years. About 70% of patients continued treatment with Orenitram for at least a year. The mean dose was 4.2 mg BID at one year. The adverse reactions were similar to those observed in the placebo-controlled trials.

The safety of Orenitram was also evaluated in an open-label study transitioning patients from Remodulin. The safety profile during this study was similar to that observed in the three pivotal studies.

The following adverse reactions have been identified during postapproval use of Orenitram: dizziness, dyspepsia, vomiting, myalgia, and arthralgia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil in healthy adult volunteers increases exposure to treprostinil. Reduce the starting dose of Orenitram to 0.125 mg BID and use 0.125 mg BID increments not more frequently than every 3 to 4 days [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3)].

Risk Summary

Limited published data from case reports with Orenitram use in pregnant women are not sufficient to assess for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations). Animal reproductive studies with treprostinil diolamine administered orally have shown an adverse effect on the fetus. In rats, administration of treprostinil to pregnant rats during the period of organogenesis at doses ≥10 mg/kg/day (approximately 15 times the human exposure at the dose of 3.5 mg BID on an AUC basis) resulted in decreased pregnancy rate, increased post-implantation loss, and decreased fetal viability and growth. In rabbits, teratogenicity and decreased fetal viability and growth were observed at doses ≥1.5 mg/kg/day (approximately 7 times the human exposure at the dose of 3.5 mg BID on an AUC basis) (see Animal Data).

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and embryo-fetal risk

Pulmonary arterial hypertension in pregnancy increases the risk of maternal heart failure, stroke and death, preterm delivery, low birth weight, and stillbirth.

Data

Animal Data

In pregnant rats, reversible, dose-dependent decreases in body weight gain and food consumption were observed during the first four days of dosing in animals administered 10, 20, and 30 mg/kg/day treprostinil diolamine. In a dose range-finding study, there was a 17% decrease in the pregnancy rate in the animals administered 20 and 30 mg/kg/day. One dam in each of the 20 and 30 mg/kg/day had litters with no viable fetuses. In the definitive study (0, 5, 10, and 20 mg/kg/day), there were four treatment-related deaths, and a 32% decrease in the pregnancy rate for rats administered 20 mg/kg/day. There was an 8% decrease in the pregnancy rate in the animals administered 10 mg/kg/day. Across both studies, an increase in post-implantation loss was observed in animals administered 10 to 30 mg/kg/day, and a significant decrease in the mean number of live births was seen at dose levels ≥10 mg/kg/day. The no observed adverse effect level was 5 mg/kg/day (maternal, fetal viability and growth), and 20 mg/kg/day (teratogenicity), the highest dose tested in the definitive study. The exposures at 5 and 20 mg/kg/day doses represent 8 and 33 times, respectively, the human exposure at the dose of 3.5 mg BID on an AUC basis.

For F1 progeny, a decreased copulation index was observed at the 5 and 10 mg/kg/day treprostinil diolamine dose levels in rats. The no observed effect levels for physical development, reflex development, exploratory behavior, learning and memory, and sexual maturation was 10 mg/kg/day. The no observed effect level for F1 progeny general development (based on body weight) was 10 mg/kg/day for females and ≤2.5 mg/kg/day for males; the no observed effect level for F1 reproductive performance was 2.5 mg/kg/day (approximately 4 times the human exposure at the dose of 3.5 mg BID on an AUC basis).

In pregnant rabbits, the primary maternal adverse effect was gastrointestinal disturbance; dose-dependent decreases in mean body weight, body weight gain, and food consumption were observed. During the post-dose phase, the effect was reversed. In a dose range-finding study, there was a 17% decrease in the pregnancy rate for animals administered 4 mg/kg/day. A dose-dependent increase in post-implantation loss was observed. Two dams administered 4 mg/kg/day had litters with no viable fetuses; the mean fetal weight was slightly decreased in animals administered 4 mg/kg/day. In the definitive study, mean fetal weights were significantly decreased in animals administered 0.5 to 3 mg/kg/day of treprostinil diolamine. At doses of 1.5 and 3 mg/kg/day, external fetal and soft tissue malformations were observed in a few fetuses, and the total fetal skeletal malformations were significantly increased. The no observed adverse effect level was less than 0.5 mg/kg/day (maternal), 1.5 mg/kg/day (fetal viability and growth), and 0.5 mg/kg/day (teratogenicity). The 0.5 mg/kg/day dose represents about 3 times the human exposure at the dose of 3.5 mg BID on an AUC basis.

Risk Summary

There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production.

Safety and effectiveness in pediatric patients have not been established.

Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic or cardiac function, and of concomitant disease or other drug therapy.

There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients [see Dosage and Administration (2.3), Contraindications (4), and Clinical Pharmacology (12.3)].

No dose adjustments are required in patients with renal impairment. Orenitram is not removed by dialysis [see Clinical Pharmacology (12.3)].

Signs and symptoms of overdose with Orenitram during clinical trials reflect its dose-limiting pharmacologic effects and include severe headache, nausea, vomiting, diarrhea, and hypotension. Treat supportively.

{ "type": "p", "children": [], "text": "Signs and symptoms of overdose with Orenitram during clinical trials reflect its dose-limiting pharmacologic effects and include severe headache, nausea, vomiting, diarrhea, and hypotension. Treat supportively." }

Orenitram is an extended-release osmotic tablet for oral administration. Orenitram is formulated as the diolamine salt of treprostinil, a tricyclic benzindene analogue of prostacyclin. The chemical name is Acetic acid, 2-[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]-, complexed with 2,2'-iminobis[ethanol] (1:1). The molecular formula is C23H34O5∙C4H11NO2, the molecular weight is 495.65, and it has the following structural formula:

{ "type": "p", "children": [], "text": "Orenitram is an extended-release osmotic tablet for oral administration. Orenitram is formulated as the diolamine salt of treprostinil, a tricyclic benzindene analogue of prostacyclin. The chemical name is Acetic acid, 2-[[(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H-benz[f]inden-5-yl]oxy]-, complexed with 2,2'-iminobis[ethanol] (1:1). The molecular formula is C23H34O5∙C4H11NO2, the molecular weight is 495.65, and it has the following structural formula:" }

Orenitram tablets are formulated in five strengths, which contain 0.125 mg of treprostinil (equivalent to 0.159 mg treprostinil diolamine), 0.25 mg of treprostinil (equivalent to 0.317 mg treprostinil diolamine), 1 mg of treprostinil (equivalent to 1.27 mg treprostinil diolamine), 2.5 mg of treprostinil (equivalent to 3.17 mg treprostinil diolamine), or 5 mg of treprostinil (equivalent to 6.35 mg treprostinil diolamine). The formulations also contain xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. In addition, tablets may contain colorants FD&C Blue #2, iron oxide yellow, and iron oxide red. The imprint ink contains shellac glaze, ethanol, isopropyl alcohol USP, iron oxide black, n-butyl alcohol, and propylene glycol.

{ "type": "p", "children": [], "text": "Orenitram tablets are formulated in five strengths, which contain 0.125 mg of treprostinil (equivalent to 0.159 mg treprostinil diolamine), 0.25 mg of treprostinil (equivalent to 0.317 mg treprostinil diolamine), 1 mg of treprostinil (equivalent to 1.27 mg treprostinil diolamine), 2.5 mg of treprostinil (equivalent to 3.17 mg treprostinil diolamine), or 5 mg of treprostinil (equivalent to 6.35 mg treprostinil diolamine). The formulations also contain xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. In addition, tablets may contain colorants FD&C Blue #2, iron oxide yellow, and iron oxide red. The imprint ink contains shellac glaze, ethanol, isopropyl alcohol USP, iron oxide black, n-butyl alcohol, and propylene glycol." }

Orenitram is designed to release treprostinil at a near zero-order rate using an osmotic tablet technology. The tablet core is coated with a semi-permeable membrane and has a laser-drilled aperture through the membrane. Upon contact with water (e.g., after ingestion), the core tablet absorbs water through the semi-permeable membrane. The water dissolves the water-soluble treprostinil diolamine and the water-soluble osmotic excipients, which creates hydrostatic pressure within the membrane, eventually forcing the drug across the membrane at a controlled rate.

{ "type": "p", "children": [], "text": "Orenitram is designed to release treprostinil at a near zero-order rate using an osmotic tablet technology. The tablet core is coated with a semi-permeable membrane and has a laser-drilled aperture through the membrane. Upon contact with water (e.g., after ingestion), the core tablet absorbs water through the semi-permeable membrane. The water dissolves the water-soluble treprostinil diolamine and the water-soluble osmotic excipients, which creates hydrostatic pressure within the membrane, eventually forcing the drug across the membrane at a controlled rate. " }

The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds, inhibition of platelet aggregation, and inhibition of smooth muscle cell proliferation.

In a clinical trial of 240 healthy adult volunteers, single doses of inhaled treprostinil 54 µg (the target clinical dose) and 84 µg (supratherapeutic inhalation dose) prolonged the corrected QTc interval by approximately 10 msec. The QTc effect dissipated rapidly as the concentration of treprostinil decreased. Orenitram has not been evaluated in a thorough QTc study.

In patients with PAH, pharmacokinetics of treprostinil is dose-proportional for systemic exposure (AUC0-t) over the dose range from 0.5 to 15 mg BID. Upon repeat administration with a BID regimen, the accumulation in the systemic exposures to treprostinil is minimal and results in a peak-to-trough ratio of approximately 7. However, a TID regimen will reduce the peak-to-trough fluctuations to approximately 2.5 for the same total daily dose.

Absorption

The absolute oral bioavailability of Orenitram is approximately 17%. Maximum treprostinil concentrations occur between approximately 4 and 6 hours following Orenitram administration. Time to reach steady-state concentrations for both BID and TID regimens is approximately 1 to 2 days.

The absorption of Orenitram is affected by food. The AUCinf of treprostinil was increased by 49% and the Cmax was increased by an average of 13% when Orenitram was administered following a high-fat, high-calorie meal compared to fasting conditions in healthy volunteers. The relative bioavailability of treprostinil following oral administration of Orenitram 1 mg is not significantly altered by meal types ranging from 250 to 500 calories in healthy volunteers.

When Orenitram 1 mg was administered with alcohol at 0.5 mg/kg or the equivalent of 3 servings (at the same time, or ± 1 hour relative to alcohol consumption), there was no significant change (10% to 20% increase) in the exposure to treprostinil compared to Orenitram administered alone.

Distribution

The treprostinil component of Orenitram is highly bound to human plasma proteins, approximately 96% over a treprostinil concentration range of 0.01 to 10 µg/mL.

Metabolism and Excretion

In a study conducted in healthy volunteers using [14C] treprostinil, treprostinil was extensively metabolized on the side chain of the molecule via oxidation, oxidative cleavage, dehydration, and glucuronic acid conjugation. Treprostinil is primarily metabolized by CYP2C8 and to a lesser extent by CYP2C9. No new major metabolites are found upon oral administration compared to parenteral administration of treprostinil. Only 1.13% and 0.19% is excreted as unchanged parent drug in the feces and urine, respectively. Based on in vitro studies, treprostinil does not inhibit or induce major CYP enzymes [see Drug Interactions (7.1)].

Specific Populations

Hepatic Impairment: In subjects with mild (n=8) hepatic impairment, administration of a single 1 mg dose of Orenitram resulted in a mean Cmax and an AUC0-inf that were 1.6- and 2.1-fold values seen in healthy subjects, respectively. With moderate impairment (n=8), the corresponding ratios were 4.0- and 4.8-fold, and with severe impairment (n=6), they were 4.8- and 7.6-fold [see Dosage and Administration (2.3), Contraindications (4), and Use in Specific Populations (8.6)].

Renal Impairment: In patients with severe renal impairment requiring dialysis (n=8), administration of a single 1 mg dose of Orenitram pre- and post-dialysis resulted in an AUC0-inf that was not significantly altered compared to healthy subjects.

Drug Interactions

Results of drug interaction studies are shown in Figure 1. Only for the strong CYP2C8 inhibitor does the interaction affect dosing [see Dosage and Administration (2.4)].

Figure 1: Impact of Co-Administered Drugs on the Systemic Exposure of Treprostinil 1 mg Compared to Orenitram Administered Alone

Warfarin: A drug interaction study was carried out with Remodulin co-administered with warfarin (25 mg/day) in healthy volunteers. There was no clinically significant effect of either medication on the pharmacokinetics of treprostinil. Additionally, treprostinil did not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R- and S-warfarin and the international normalized ratio (INR) in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min.

Treprostinil diolamine did not demonstrate any carcinogenic effects in mouse or rat carcinogenicity studies. Oral administration of treprostinil diolamine to Tg.rasH2 mice at 0, 5, 10, and 20 mg/kg/day in males and 0, 3, 7.5, and 15 mg/kg/day in females daily for 26 weeks did not significantly increase the incidence of tumors. Oral administration of treprostinil diolamine to Sprague Dawley rats at 0, 1, 3, and 10 mg/kg/day daily for 104 weeks did not significantly increase the incidence of tumors. The exposures obtained at the highest dose levels used in males and females are about 13- and 18-fold, respectively, the human exposure at the dose of 3.5 mg BID on an AUC basis.

In vitro genotoxicity studies with high doses of treprostinil did not demonstrate any mutagenic or clastogenic effects. Treprostinil diolamine was tested in vivo in a rat micronucleus assay and did not induce an increased incidence of micronucleated polychromatic erythrocytes.

In rats, treatment with treprostinil diolamine had no effect on reproductive performance or sperm motility at doses up to 10 mg/kg/day. The exposures at this dose level are about 6- (male) to 11- (female) fold the human exposure at the dose of 3.5 mg BID on an AUC basis.

Four multicenter, randomized, double-blind studies were conducted and compared Orenitram to placebo in a total of 349 (Study 1), 350 (Study 2), 310 (Study 3), and 690 (Study 4) patients with PAH.

Study 1 (effect seen with no background vasodilator)

Study 1 was a 12-week, randomized (2:1 Orenitram to placebo), double-blind, placebo-controlled, international efficacy and safety study of Orenitram in patients with WHO Group 1 PAH not currently receiving PAH therapy. The primary efficacy endpoint was placebo-corrected change in six-minute walk distance (6MWD) from Baseline to Week 12. Study drug dose was titrated to a maximum of 12 mg BID based on clinical response and study drug tolerability. Study 1 enrolled 349 patients (overall analysis population) who were not receiving any PAH medication. At the beginning of the study, subjects were dosed with only the 1 mg tablets with 0.5 and 0.25 mg tablets introduced at sequentially later dates during the study. The primary analysis population consisted of the 228 patients who had access to the 0.25 mg tablet at the time of randomization. Patients were administered Orenitram or placebo twice daily, with the doses titrated to effect over the course of the 12-week trial. Patients were in WHO functional class II (~33%) and class III (~66%) with either idiopathic or heritable PAH (~75%), collagen vascular disease associated PAH (~19%), or PAH associated with HIV (1%) or congenital heart defect (5%) or other conditions (~6%). The patients' mean baseline 6MWD was approximately 330 meters. In the primary analysis population, 17% of patients discontinued Orenitram compared to 14% of patients on placebo.

The primary efficacy endpoint of the trial was the change in 6MWD at 12 weeks for the primary analysis population. Analysis of Study 1 results demonstrated that those patients receiving Orenitram compared to patients receiving placebo improved their median change in 6MWD by approximately 23 meters (p=0.013) as compared to patients receiving placebo as demonstrated in (Figure 2). The within group median change from baseline was +25 meters for Orenitram and -5 meters for placebo at Week 12 (N=228). Mean dose (±SD) in the Orenitram group was 2.3 ± 1.3, 3.2 ± 1.9, and 3.4 ± 1.9 mg BID at Weeks 4, 8, and 12, respectively, with a maximum dose of 12 mg BID. The distribution of the 6MWD change from baseline at Week 12 was also plotted across the range of observed values (Figure 3).

Figure 2: Estimate of Treatment Effect by Visit for the Primary Analysis Population (Study 1)

Figure 3: Plot of the Distribution of Peak 6MWD Changes at Week 12 for the Primary Analysis Population (Study 1)

The placebo-corrected median treatment effect on 6MWD was estimated within various subpopulations defined by age, gender, disease etiology, and baseline 6MWD (Figure 4).

Figure 4: Placebo Corrected Median Treatment Effect (with 95% CI) on 6MWD Change from Baseline at Week 12 for Various Subgroups in the Primary Analysis Population (Study 1)

Studies 2 and 3 (no effect on a background of ERA, PDE-5 inhibitor, or both)

Studies 2 (N=350) and 3 (N=310) were 16-week, randomized, double-blind, placebo-controlled, international efficacy and safety studies of Orenitram in patients with WHO Group 1 PAH. The primary efficacy endpoint was placebo-corrected change in 6MWD from Baseline to Week 16. Patients were in WHO functional class II (~23%) and class III (~77%) with either idiopathic or heritable PAH (~66%), collagen vascular disease associated PAH (~29%), or PAH associated with HIV (1%) or congenital heart defect (4%). The patients' mean baseline 6MWD was approximately 340 meters. Approximately 40% were receiving both an ERA and a PDE-5 inhibitor. The results did not demonstrate a benefit in exercise testing with median 6MWD at Week 16.

Study 4 (effect seen with a single background PAH therapy)

The effect of Orenitram on the progression of PAH was demonstrated in an international, multicenter, double-blind, event-driven study in patients with WHO Group 1 PAH randomized 1:1 to Orenitram or placebo (Study 4). The primary efficacy endpoint was the time to first clinical worsening (morbidity or mortality) event. Study drug dose was titrated starting at 0.125 mg TID to a maximum of 12 mg TID based on clinical response and study drug tolerability. Study 4 enrolled a total of 690 patients (primary efficacy analysis population) who were currently receiving a single approved PAH therapy (PDE-5 inhibitor or soluble guanylate cyclase (sGC) [72%]; ERA [28%]). The median age was 43 years and most patients were white (52%) and female (79%). The majority of patients were lower risk in WHO functional class II (63%) with a mean (±SD) baseline 6MWD of 396 (±96) meters. Most patients had either idiopathic or heritable PAH (63%) or collagen vascular disease associated PAH (26%).

Patients treated with Orenitram achieved a median dose of 3.6 mg TID at Week 24, which continued to increase until approximately Week 60 where the median dose of Orenitram was approximately 5 mg TID.

Treatment with Orenitram resulted in a significant increase in the time to first clinical worsening event compared with patients who received placebo, which was associated with a reduction in the risk of an event (HR=0.75 [95% CI; 0.57, 0.99]; p=0.039; Figure 5). The beneficial effect of Orenitram was primarily attributable to a delay in disease progression—defined as a 15% decline in 6MWD plus an increase in either WHO Functional Class or worsening of signs or symptoms of right heart failure—(HR=0.39 [95% CI; 0.23, 0.66]; Figure 6), but there was no effect on the other components of clinical worsening (Table 2).

Figure 5: Kaplan-Meier Plot of Time to Clinical Worsening Events for the Primary Analysis Population (Study 4)

<div class="scrollingtable"><table width="75%"> <caption> <span>Table 2: Primary Endpoint Events (Study 4)</span> </caption> <col align="left" valign="top" width="10"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="25%"/> <col align="center" valign="top" width="10%"/> <col align="center" valign="top" width="10%"/> <col align="left" valign="top" width="20%"/> <thead> <tr class="Botrule First Last"> <th align="left" class="Lrule Rrule" colspan="3"></th><th align="center" class="Rrule">Orenitram<br/>% N=346</th><th align="center" class="Rrule">Placebo<br/>% N=344</th><th align="left" class="Rrule">HR (95% CI)</th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left" colspan="6">6MWD, 6-minute walk distance; CI, confidence interval; HR, hazard ratio; IV PGI<span class="Sub">2</span>, intravenously administered prostacyclin; PAH, pulmonary arterial hypertension; RHF, right heart failure; WHO, World Health Organization</td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Clinical worsening</span></td><td align="center" class="Rrule">26</td><td align="center" class="Rrule">36</td><td align="left" class="Rrule">0.75 (0.57, 0.99)</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" rowspan="5" valign="middle"><span class="Bold">Any of these</span></td><td align="left" class="Rrule" colspan="2"><span class="Bold">All-cause mortality</span></td><td align="center" class="Rrule">4.3</td><td align="center" class="Rrule">4.1</td><td align="left" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Hospitalization for PAH</span></td><td align="center" class="Rrule">10</td><td align="center" class="Rrule">10</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Inhaled/IV PGI<span class="Sub">2</span></span></td><td align="center" class="Rrule">0.6</td><td align="center" class="Rrule">1.5</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Unsatisfactory long-term clinical response</span></td><td align="center" class="Rrule">5.5</td><td align="center" class="Rrule">5.8</td><td align="center" class="Rrule"></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Disease progression</span></td><td align="center" class="Rrule">5.5</td><td align="center" class="Rrule">14.5</td><td align="left" class="Rrule">0.39 (0.23, 0.66)</td> </tr> <tr> <td align="left" class="Lrule Rrule"></td><td align="left" class="Botrule Rrule"><span class="Bold">This →</span></td><td align="left" class="Botrule Rrule"><span class="Bold">15% decrease in 6MWD</span></td><td align="center" class="Botrule Rrule">5.5</td><td align="center" class="Botrule Rrule">14.5</td><td align="left" class="Botrule Rrule"></td> </tr> <tr> <td align="left" class="Lrule Rrule"></td><td align="left" class="Rrule"><span class="Bold">Plus one of these</span></td><td align="left" class="Botrule Rrule"><span class="Bold">Increase in WHO functional class</span></td><td align="center" class="Botrule Rrule">2.6</td><td align="center" class="Botrule Rrule">8.1</td><td align="left" class="Botrule Rrule"></td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule"></td><td align="center" class="Rrule"></td><td align="left" class="Rrule"><span class="Bold">Increased RHF symptoms</span></td><td align="center" class="Rrule">2.9</td><td align="center" class="Rrule">6.4</td><td align="left" class="Rrule"></td> </tr> </tbody> </table></div>

Figure 6: Kaplan-Meier Plot of Time to Disease Progression for the Primary Analysis Population (Study 4)

The treatment effect on time to first clinical worsening event due to disease progression was consistent for various subgroups defined by age, sex, baseline 6MWD, WHO functional class, disease etiology, geographical regions, and background therapy (Figure 7).

Figure 7: Forest Plot of Subgroup Analyses of Time to Disease Progression for Various Subgroups in the Primary Analysis Population (Study 4)

Long-Term Treatment of Pulmonary Arterial Hypertension

Patients (N=824) from the placebo-controlled studies entered a long-term, uncontrolled, open-label extension study. The average exposure to Orenitram was approximately 2 years with a maximum exposure of approximately 6 years. The dose of Orenitram continued to increase over time with doses (mean ± SD) of 3.6 ± 2.7, 4.2 ± 3.1, and 5 ± 3.7 mg BID at 6 (n=649), 12 (n=433), and 24 months (n=238), respectively, with a maximum dose of 21 mg BID. Reasons for discontinuation from the study included adverse event (16%), progression of disease (15%), death (13%), and withdrawn consent (7%). In the 522 subjects that completed the 12-month efficacy assessment, their mean 6MWD improved by 24 meters compared to baseline (30 meters in monotherapy patients and 20 meters when Orenitram was used in combination with an ERA and/or a PDE-5 inhibitor). Of the patients that remained in the study, overall survival was 92%, 87%, and 82% at the end of 1, 2, and 3 years, respectively, with progression-free survival (progression defined as death, discontinuation, or addition of a PAH therapy) of 74%, 61%, and 47%. Without a control group, these data must be interpreted cautiously.

Remodulin to Orenitram Transition Study

A 24-week, multicenter, open-label study enrolled 33 WHO Group 1 patients on stable doses of Remodulin. All patients received background therapy with a PDE-5 inhibitor and/or ERA. Patients were WHO functional class I or II and hemodynamically stable at baseline with a cardiac index >2.2 L/m2, RAP <11 mmHg, and PVR <10 Wood units. The primary endpoint of the study was the safety and tolerability of the transition. Successful transition was defined as transition from Remodulin to Orenitram at Week 4 (no longer receiving Remodulin) and clinically maintained on Orenitram through Week 24 (as measured by 6MWD and hemodynamics).

All patients transitioned from Remodulin to Orenitram (median time to transition of 3 days) with thirty-one patients (94%) completing transition in 5 days (range 2 to 29 days). Two subjects discontinued Orenitram. After 24 weeks of treatment with Orenitram, 6MWD and hemodynamics remained stable. Without a control group, these data must be interpreted cautiously.

Orenitram is an 8-mm round biconvex tablet with strength identified by color and print and supplied as follows:

<div class="scrollingtable"><table width="95%"> <col align="center" valign="bottom" width="16%"/> <col align="center" valign="bottom" width="16%"/> <col align="center" valign="bottom" width="16%"/> <col align="center" valign="bottom" width="17%"/> <col align="center" valign="bottom" width="17%"/> <col align="center" valign="bottom" width="18%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Strength</th><th align="center" class="Rrule">Color</th><th align="center" class="Rrule">Printing on Tablets</th><th align="center" class="Rrule">NDC #<br/>100-Count Bottle</th><th align="center" class="Rrule">NDC #<br/>10-Count Bottle</th><th align="center" class="Rrule">NDC #<br/>10-Count Carton (Unit-Dose Blister)</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">0.125 mg</td><td align="center" class="Rrule">White</td><td align="center" class="Rrule">UT 0.125</td><td align="center" class="Rrule">66302-300-01</td><td align="center" class="Rrule">66302-300-10</td><td align="center" class="Rrule">66302-300-02</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">0.25 mg</td><td align="center" class="Rrule">Green</td><td align="center" class="Rrule">UT 0.25</td><td align="center" class="Rrule">66302-302-01</td><td align="center" class="Rrule">66302-302-10</td><td align="center" class="Rrule">66302-302-02</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">1 mg</td><td align="center" class="Rrule">Yellow</td><td align="center" class="Rrule">UT 1</td><td align="center" class="Rrule">66302-310-01</td><td align="center" class="Rrule">66302-310-10</td><td align="center" class="Rrule">66302-310-02</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">2.5 mg</td><td align="center" class="Rrule">Pink</td><td align="center" class="Rrule">UT 2.5</td><td align="center" class="Rrule">66302-325-01</td><td align="center" class="Rrule">66302-325-10</td><td align="center" class="Rrule">66302-325-02</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">5 mg</td><td align="center" class="Rrule">Red</td><td align="center" class="Rrule">UT 5</td><td align="center" class="Rrule">66302-350-01</td><td align="center" class="Rrule">66302-350-10</td><td align="center" class="Rrule">66302-350-02</td> </tr> </tbody> </table></div>

Titration Kits for Orenitram are supplied in the following configurations:

<div class="scrollingtable"><table width="75%"> <col align="center" valign="middle" width="15%"/> <col align="left" valign="top" width="65%"/> <col align="center" valign="middle" width="20%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule">Titration Kit</th><th align="center" class="Rrule">Blister Configurations</th><th align="center" class="Rrule">NDC #</th> </tr> </thead> <tbody> <tr class="Botrule First"> <td align="center" class="Lrule Rrule">Month 1 containing four weekly cartons</td><td align="left" class="Rrule">Seven daily wallet blister packs in each weekly carton containing the following total number of tablets:<ul class="Disc"> <li>Week 1 (twenty-one × 0.125 mg tablets)</li> <li>Week 2 (forty-two × 0.125 mg tablets)</li> <li>Week 3 (twenty-one × 0.125 mg tablets and twenty-one × 0.25 mg tablets)</li> <li>Week 4 (forty-two × 0.125 mg tablets and twenty-one × 0.25 mg tablets)</li> </ul> </td><td align="center" class="Rrule">66302-361-28</td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule">Month 2 containing four weekly cartons</td><td align="left" class="Rrule">Seven daily wallet blister packs in each weekly carton containing the following total number of tablets:<ul class="Disc"> <li>Week 5 (twenty-one × 0.125 mg tablets and forty-two × 0.25 mg tablets)</li> <li>Week 6 (forty-two × 0.125 mg tablets and forty-two × 0.25 mg tablets)</li> <li>Week 7 (twenty-one × 0.125 mg tablets and sixty-three × 0.25 mg tablets)</li> <li>Week 8 (forty-two × 0.125 mg tablets and sixty-three × 0.25 mg tablets)</li> </ul> </td><td align="center" class="Rrule">66302-362-56</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule">Month 3 containing four weekly cartons</td><td align="left" class="Rrule">Seven daily wallet blister packs in each weekly carton containing the following total number of tablets:<ul class="Disc"> <li>Week 9 (twenty-one × 0.125 mg tablets and twenty-one × 1 mg tablets)</li> <li>Week 10 (forty-two × 0.125 mg tablets and twenty-one × 1 mg tablets)</li> <li>Week 11 (twenty-one × 0.125 mg tablets, twenty-one × 0.25 mg tablets, and twenty-one × 1 mg tablets)</li> <li>Week 12 (forty-two × 0.125 mg tablets, twenty-one × 0.25 mg tablets, and twenty-one × 1 mg tablets)</li> </ul> </td><td align="center" class="Rrule">66302-363-84</td> </tr> </tbody> </table></div>

Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep out of reach of children.

See FDA-approved patient labeling (Patient Information).

{ "type": "p", "children": [], "text": "\nSee FDA-approved patient labeling (Patient Information).\n" }

Tell patients:

{ "type": "p", "children": [], "text": "Tell patients: " }

{ "type": "ul", "children": [ "Abrupt discontinuation of therapy could result in worsening of PAH symptoms.", "Take Orenitram with food.", "Swallow Orenitram tablets whole. Do not split, chew, crush, or break. Do not take a tablet that is damaged or broken.", "The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the feces as an insoluble shell." ], "text": "" }

©Copyright 2023 United Therapeutics Corp. All rights reserved.

{ "type": "p", "children": [], "text": "\n©Copyright 2023 United Therapeutics Corp. All rights reserved." }

United Therapeutics Corp.Research Triangle Park, NC 27709

{ "type": "p", "children": [], "text": "United Therapeutics Corp.Research Triangle Park, NC 27709" }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="50%"/> <col align="left" valign="top" width="30%"/> <col align="right" valign="top" width="20%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="2" valign="top">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="right" valign="top">Revised: 02/2023</td> </tr> </tfoot> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" colspan="3"><span class="Bold">Patient Information<br/>Orenitram<span class="Sup">(®)</span> (oh-REN-i-tram)<br/>(treprostinil) extended-release tablets</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What is Orenitram?</span> <ul class="Disc"> <li>Orenitram is a prescription medicine used to treat pulmonary arterial hypertension (PAH) which is high blood pressure in the arteries of your lungs. </li> <li>Orenitram can help slow down the progression of your disease and improve your ability to exercise.</li> </ul> It is not known if Orenitram is safe and effective in children. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Do not take Orenitram </span> if you have severe liver problems.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">Before taking Orenitram, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul> <li>have liver problems</li> <li>have diverticulosis</li> <li>are pregnant or plan to become pregnant. It is not known if Orenitram will harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. It is not known if Orenitram passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Orenitram. </li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Orenitram and other medicines may affect each other causing side effects. Do not start any new medicine until you check with your healthcare provider.<br/>Especially tell your healthcare provider if you take another medicine that contains treprostinil, such as Remodulin<span class="Sup">®</span>, Tyvaso<span class="Sup">®</span>, or Tyvaso DPI<span class="Sup">®</span>.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I take Orenitram?</span> <ul> <li>Take Orenitram exactly as your healthcare provider tells you to take it.</li> <li>Your healthcare provider will slowly increase your dose to find the dose of Orenitram that is right for you.</li> <li>If you take the medicine Remodulin and your healthcare provider is switching you to Orenitram, your healthcare provider will decrease your dose of Remodulin over a period of time when you start taking Orenitram.</li> <li> <span class="Bold">Do not change your dose or suddenly stop taking Orenitram without first talking to your healthcare provider.</span> </li> <li>Orenitram is usually taken 3 times a day (about every 8 hours) or 2 times a day (about every 12 hours). Your healthcare provider will tell you how often you should take Orenitram. If you have side effects, your healthcare provider may tell you to change your dose or when you take Orenitram.</li> <li>Take Orenitram with food. </li> <li>Swallow Orenitram tablets whole. Do not split, chew, crush, or break your Orenitram tablets. Do not take Orenitram tablets that are damaged or broken. <span class="Bold">If Orenitram tablets are not taken whole, they may release too much medicine at one time. This can lead to side effects.</span> </li> <li>You may see the tablet shell in your stools (bowel movements). This is usually normal. The tablet shell is not digested. If you have diverticulosis, the tablet shell may get stuck in a blind pouch or diverticulum in your intestine.</li> <li>If you miss your dose of Orenitram, take the missed dose as soon as possible with food.</li> <li>If you miss 2 or more doses of Orenitram, call your healthcare provider to see if you need to change your dose.</li> <li>If you take too much Orenitram, call your healthcare provider or go to the nearest hospital emergency room right away. </li> </ul> </td> </tr> <tr> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the possible side effects of Orenitram?<br/>Orenitram can cause serious side effects, including worsening of PAH symptoms.</span> <ul class="Disc"> <li>Stopping Orenitram suddenly may cause worsening of your PAH symptoms. <span class="Bold">Do not change your dose or suddenly stop taking Orenitram without first talking to your healthcare provider.</span> </li> </ul> <span class="Bold">The most common side effects of Orenitram include:</span></td> </tr> <tr> <td align="left" class="Lrule"> <ul class="Disc"> <li>headache</li> <li>diarrhea</li> <li>nausea</li> <li>vomiting</li> </ul> </td><td align="left" class="Rrule" colspan="2"> <ul class="Disc"> <li>flushing</li> <li>pain in arms and legs</li> <li>jaw pain</li> </ul> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" colspan="3">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.<br/>These are not all of the possible side effects of Orenitram. For more information, ask your healthcare provider or pharmacist. <br/>Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">How should I store Orenitram?</span> <ul> <li>Store at 68°F to 77°F (20°C to 25°C).</li> </ul> <span class="Bold">Keep Orenitram and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">General information about the safe and effective use of Orenitram.</span> <br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet.<br/> Do not use Orenitram for a condition for which it was not prescribed. Do not give Orenitram to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about Orenitram that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="3"><span class="Bold">What are the ingredients in Orenitram?</span> <br/> <span class="Bold">Active ingredient:</span> treprostinil diolamine<br/> <span class="Bold">Inactive ingredients:</span> xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. In addition, tablets may contain colorants FD&amp;C Blue #2, iron oxide yellow, and iron oxide red. The imprint ink contains shellac glaze, ethanol, isopropyl alcohol, iron oxide black, n-butyl alcohol, and propylene glycol.<br/>United Therapeutics Corp., Research Triangle Park, NC 27709 USA<br/>Copyright 2023, United Therapeutics Corp. All rights reserved.<br/>ORENITRAM is a registered trademark of United Therapeutics Corp.<br/>For more information, go to www.orenitram.com or call 1-877-864-8437.</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"50%\"/>\n<col align=\"left\" valign=\"top\" width=\"30%\"/>\n<col align=\"right\" valign=\"top\" width=\"20%\"/>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\" colspan=\"2\" valign=\"top\">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align=\"right\" valign=\"top\">Revised: 02/2023</td>\n</tr>\n</tfoot>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Patient Information<br/>Orenitram<span class=\"Sup\">(®)</span> (oh-REN-i-tram)<br/>(treprostinil) extended-release tablets</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What is Orenitram?</span>\n<ul class=\"Disc\">\n<li>Orenitram is a prescription medicine used to treat pulmonary arterial hypertension (PAH) which is high blood pressure in the arteries of your lungs. </li>\n<li>Orenitram can help slow down the progression of your disease and improve your ability to exercise.</li>\n</ul>\t\t\t\t\t\t\t\t\t\tIt is not known if Orenitram is safe and effective in children. \t\t\t\t\t\t\t\t\t</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Do not take Orenitram </span> if you have severe liver problems.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">Before taking Orenitram, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul>\n<li>have liver problems</li>\n<li>have diverticulosis</li>\n<li>are pregnant or plan to become pregnant. It is not known if Orenitram will harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if Orenitram passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby during treatment with Orenitram. </li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take</span>, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Orenitram and other medicines may affect each other causing side effects. Do not start any new medicine until you check with your healthcare provider.<br/>Especially tell your healthcare provider if you take another medicine that contains treprostinil, such as Remodulin<span class=\"Sup\">®</span>, Tyvaso<span class=\"Sup\">®</span>, or Tyvaso DPI<span class=\"Sup\">®</span>.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I take Orenitram?</span>\n<ul>\n<li>Take Orenitram exactly as your healthcare provider tells you to take it.</li>\n<li>Your healthcare provider will slowly increase your dose to find the dose of Orenitram that is right for you.</li>\n<li>If you take the medicine Remodulin and your healthcare provider is switching you to Orenitram, your healthcare provider will decrease your dose of Remodulin over a period of time when you start taking Orenitram.</li>\n<li>\n<span class=\"Bold\">Do not change your dose or suddenly stop taking Orenitram without first talking to your healthcare provider.</span>\n</li>\n<li>Orenitram is usually taken 3 times a day (about every 8 hours) or 2 times a day (about every 12 hours). Your healthcare provider will tell you how often you should take Orenitram. If you have side effects, your healthcare provider may tell you to change your dose or when you take Orenitram.</li>\n<li>Take Orenitram with food. </li>\n<li>Swallow Orenitram tablets whole. Do not split, chew, crush, or break your Orenitram tablets. Do not take Orenitram tablets that are damaged or broken. <span class=\"Bold\">If Orenitram tablets are not taken whole, they may release too much medicine at one time. This can lead to side effects.</span>\n</li>\n<li>You may see the tablet shell in your stools (bowel movements). This is usually normal. The tablet shell is not digested. If you have diverticulosis, the tablet shell may get stuck in a blind pouch or diverticulum in your intestine.</li>\n<li>If you miss your dose of Orenitram, take the missed dose as soon as possible with food.</li>\n<li>If you miss 2 or more doses of Orenitram, call your healthcare provider to see if you need to change your dose.</li>\n<li>If you take too much Orenitram, call your healthcare provider or go to the nearest hospital emergency room right away. </li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the possible side effects of Orenitram?<br/>Orenitram can cause serious side effects, including worsening of PAH symptoms.</span>\n<ul class=\"Disc\">\n<li>Stopping Orenitram suddenly may cause worsening of your PAH symptoms. <span class=\"Bold\">Do not change your dose or suddenly stop taking Orenitram without first talking to your healthcare provider.</span>\n</li>\n</ul>\n<span class=\"Bold\">The most common side effects of Orenitram include:</span></td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Lrule\">\n<ul class=\"Disc\">\n<li>headache</li>\n<li>diarrhea</li>\n<li>nausea</li>\n<li>vomiting</li>\n</ul>\n</td><td align=\"left\" class=\"Rrule\" colspan=\"2\">\n<ul class=\"Disc\">\n<li>flushing</li>\n<li>pain in arms and legs</li>\n<li>jaw pain</li>\n</ul>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" colspan=\"3\">Tell your healthcare provider if you have any side effect that bothers you or that does not go away.<br/>These are not all of the possible side effects of Orenitram. For more information, ask your healthcare provider or pharmacist. <br/>Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">How should I store Orenitram?</span>\n<ul>\n<li>Store at 68°F to 77°F (20°C to 25°C).</li>\n</ul>\n<span class=\"Bold\">Keep Orenitram and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">General information about the safe and effective use of Orenitram.</span>\n<br/>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet.<br/> Do not use Orenitram for a condition for which it was not prescribed. Do not give Orenitram to other people, even if they have the same symptoms that you have. It may harm them. You can ask your healthcare provider or pharmacist for information about Orenitram that is written for health professionals. </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"3\"><span class=\"Bold\">What are the ingredients in Orenitram?</span>\n<br/>\n<span class=\"Bold\">Active ingredient:</span> treprostinil diolamine<br/>\n<span class=\"Bold\">Inactive ingredients:</span> xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. In addition, tablets may contain colorants FD&amp;C Blue #2, iron oxide yellow, and iron oxide red. The imprint ink contains shellac glaze, ethanol, isopropyl alcohol, iron oxide black, n-butyl alcohol, and propylene glycol.<br/>United Therapeutics Corp., Research Triangle Park, NC 27709 USA<br/>Copyright 2023, United Therapeutics Corp. All rights reserved.<br/>ORENITRAM is a registered trademark of United Therapeutics Corp.<br/>For more information, go to www.orenitram.com or call 1-877-864-8437.</td>\n</tr>\n</tbody>\n</table></div>" }

NDC 66302-300-01

{ "type": "p", "children": [], "text": "NDC 66302-300-01" }

100 Tablets

{ "type": "p", "children": [], "text": "100 Tablets" }

Orenitram® (treprostinil)Extended-ReleaseTablets

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)Extended-ReleaseTablets" }

0.125 mg

{ "type": "p", "children": [], "text": "0.125 mg" }

Swallow whole.Do not split, chew, crush,or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush,or break tablets." }

Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)EXTENDED-RELEASE TABLETS" }

0.125 mgper tablet

{ "type": "p", "children": [], "text": "0.125 mgper tablet" }

Swallow whole.Do not split, chew, crush, or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush, or break tablets." }

10 Tablets(1 x 10 tablet blister pack)

{ "type": "p", "children": [], "text": "10 Tablets(1 x 10 tablet blister pack)" }

Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient.

{ "type": "p", "children": [], "text": "Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient." }

Rx Only NDC 66302-300-02

{ "type": "p", "children": [], "text": "Rx Only NDC 66302-300-02" }

NDC 66302-302-01

{ "type": "p", "children": [], "text": "NDC 66302-302-01" }

100 Tablets

{ "type": "p", "children": [], "text": "100 Tablets" }

Orenitram® (treprostinil)Extended-ReleaseTablets

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)Extended-ReleaseTablets" }

0.25 mg

{ "type": "p", "children": [], "text": "0.25 mg" }

Swallow whole.Do not split, chew, crush,or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush,or break tablets." }

Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)EXTENDED-RELEASE TABLETS" }

0.25 mgper tablet

{ "type": "p", "children": [], "text": "0.25 mgper tablet" }

Swallow whole.Do not split, chew, crush, or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush, or break tablets." }

10 Tablets(1 x 10 tablet blister pack)

{ "type": "p", "children": [], "text": "10 Tablets(1 x 10 tablet blister pack)" }

Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient.

{ "type": "p", "children": [], "text": "Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient." }

Rx Only NDC 66302-302-02

{ "type": "p", "children": [], "text": "Rx Only NDC 66302-302-02" }

NDC 66302-310-01

{ "type": "p", "children": [], "text": "NDC 66302-310-01" }

100 Tablets

{ "type": "p", "children": [], "text": "100 Tablets" }

Orenitram® (treprostinil)Extended-ReleaseTablets

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)Extended-ReleaseTablets" }

1 mg

{ "type": "p", "children": [], "text": "1 mg" }

Swallow whole.Do not split, chew, crush,or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush,or break tablets." }

Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)EXTENDED-RELEASE TABLETS" }

1 mgper tablet

{ "type": "p", "children": [], "text": "1 mgper tablet" }

Swallow whole.Do not split, chew, crush, or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush, or break tablets." }

10 Tablets(1 x 10 tablet blister pack)

{ "type": "p", "children": [], "text": "10 Tablets(1 x 10 tablet blister pack)" }

Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient.

{ "type": "p", "children": [], "text": "Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient." }

Rx Only NDC 66302-310-02

{ "type": "p", "children": [], "text": "Rx Only NDC 66302-310-02" }

NDC 66302-325-01

{ "type": "p", "children": [], "text": "NDC 66302-325-01" }

100 Tablets

{ "type": "p", "children": [], "text": "100 Tablets" }

Orenitram® (treprostinil)Extended-ReleaseTablets

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)Extended-ReleaseTablets" }

2.5 mg

{ "type": "p", "children": [], "text": "2.5 mg" }

Swallow whole.Do not split, chew, crush,or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush,or break tablets." }

Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

{ "type": "p", "children": [], "text": "Orenitram®\n(treprostinil)EXTENDED-RELEASE TABLETS" }

2.5 mgper tablet

{ "type": "p", "children": [], "text": "2.5 mgper tablet" }

Swallow whole.Do not split, chew, crush, or break tablets.

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10 Tablets(1 x 10 tablet blister pack)

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Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient.

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Rx Only NDC 66302-325-02

{ "type": "p", "children": [], "text": "Rx Only NDC 66302-325-02" }

NDC 66302-350-01

{ "type": "p", "children": [], "text": "NDC 66302-350-01" }

100 Tablets

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Orenitram® (treprostinil)Extended-ReleaseTablets

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5 mg

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Swallow whole.Do not split, chew, crush,or break tablets.

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Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

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5 mgper tablet

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Swallow whole.Do not split, chew, crush, or break tablets.

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10 Tablets(1 x 10 tablet blister pack)

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Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient.

{ "type": "p", "children": [], "text": "Pharmacist:Dispense the accompanying Patient Information Leaflet to each patient." }

Rx Only NDC 66302-350-02

{ "type": "p", "children": [], "text": "Rx Only NDC 66302-350-02" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

NDC 66302-361-28

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Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

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Titration Kit

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Month 1

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0.125 mgper tablet

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0.25 mgper tablet

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Swallow whole.Do not split, chew, crush, or break tablets.

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Kit Contains:168 tablets (126 x 0.125 mg per tablet and42 x 0.25 mg per tablet).Monthly carton contains 4 individual weekly cartonseach with 7 daily wallet blister packs.

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Rx Only

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NDC 66302-362-56

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Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

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Titration Kit

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Month 2

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0.125 mgper tablet

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0.25 mgper tablet

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Swallow whole.Do not split, chew, crush, or break tablets.

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Kit Contains:336 tablets (126 x 0.125 mg per tablet and210 x 0.25 mg per tablet).Monthly carton contains 4 individual weekly cartonseach with 7 daily wallet blister packs.

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Rx Only

{ "type": "p", "children": [], "text": "Rx Only" }

NDC 66302-363-84

{ "type": "p", "children": [], "text": "NDC 66302-363-84" }

Orenitram® (treprostinil)EXTENDED-RELEASE TABLETS

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Titration Kit

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Month 3

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0.125 mgper tablet

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0.25 mgper tablet

{ "type": "p", "children": [], "text": "0.25 mgper tablet" }

1 mgper tablet

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Swallow whole.Do not split, chew, crush, or break tablets.

{ "type": "p", "children": [], "text": "Swallow whole.Do not split, chew, crush, or break tablets." }

Kit Contains:252 tablets (126 x 0.125 mg per tablet,42 x 0.25 mg per tablet, and 84 × 1 mg per tablet).Monthly carton contains 4 individual weekly cartonseach with 7 daily wallet blister packs.

{ "type": "p", "children": [], "text": "Kit Contains:252 tablets (126 x 0.125 mg per tablet,42 x 0.25 mg per tablet, and 84 × 1 mg per tablet).Monthly carton contains 4 individual weekly cartonseach with 7 daily wallet blister packs." }

Treprostinil injection is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%) [see Clinical Studies (14.1)].

In patients with PAH requiring transition from epoprostenol, Treprostinil injection is indicated to diminish the rate of clinical deterioration. Consider the risks and benefits of each drug prior to transition.

Treprostinil injection can be administered with or without further dilution with Sterile Diluent for Treprostinil injection or similar approved high-pH glycine diluent (e.g., Sterile Diluent for Flolan or Sterile Diluent for Epoprostenol), Sterile Water for Injection, or 0.9% Sodium Chloride Injection prior to administration. See Table 1 below for storage and administration time limits for the different diluents. Diluted Treprostinil injection has been shown to be stable at ambient temperature when stored for up to 14 days using high-pH glycine diluent at concentrations as low as 0.004 mg/mL (4,000 ng/mL). Table 1: Selection of Diluent

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="547.8935"> <colgroup> <col width="35.089209855565%"/> <col width="28.9719626168224%"/> <col width="35.9388275276126%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td class="Lrule Rrule" valign="middle"><span class="Bold"> Diluent</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Storage Limits</span> <br/> </td><td class="Rrule" valign="middle"><span class="Bold">Administration Limits</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">None<br/> </td><td class="Rrule" valign="middle">See Section 16<br/> </td><td class="Rrule" valign="middle">16 weeks at 40°C<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="top">Sterile Diluents for Treprostinil Injection, Flolan, or Epoprostenol <br/> </td><td class="Rrule" valign="middle">14 days at room temperature <br/> </td><td class="Rrule" valign="middle">48 hours at 40°C<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="top">Sterile Water for  Injection 0.9% Sodium Chloride for<br/>Injection<br/> </td><td class="Rrule" valign="middle">4 hours at room<br/>temperature or 24<br/>hours refrigerated<br/> </td><td class="Rrule" valign="middle">48 hours at 40°C<br/> </td> </tr> </tbody> </table></div>

Treprostinil injection is indicated for subcutaneous (SC) or intravenous (IV) use only as a continuous infusion. Treprostinil injection is preferably infused subcutaneously, but can be administered by a central intravenous line if the subcutaneous route is not tolerated because of severe site pain or reaction. The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, reduce the infusion rate to 0.625 ng/kg/min.

The initial dose of Treprostinil Injection should be the same as the current dose the patient is receiving using the external infusion pump at the time of transition.

The goal of chronic dosage adjustments is to establish a dose at which PAH symptoms are improved, while minimizing excessive pharmacologic effects of Treprostinil injection (headache, nausea, emesis, restlessness, anxiety, and infusion site pain or reaction).

The infusion rate should be increased in increments of 1.25 ng/kg/min per week for the first four weeks of treatment and then 2.5 ng/kg/min per week for the remaining duration of infusion, depending on clinical response. Dosage adjustments may be undertaken more often if tolerated. Avoid abrupt cessation of infusion [see Warnings and Precautions (5.2)]. Restarting a Treprostinil injection infusion within a few hours after an interruption can be done using the same dose rate. Interruptions for longer periods may require the dose of Treprostinil injection to be re-titrated.

In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Treprostinil injection to 0.625 ng/kg/min ideal body weight. Treprostinil injection has not been studied in patients with severe hepatic insufficiency [see Warnings and Precautions (5.3), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. If either particulate matter or discoloration is noted, do not use. Preparation Treprostinil injection is administered by subcutaneous or intravenous infusion at a calculated rate based on a patient’s dose (ng/kg/min), weight (kg), and the Treprostinil injection concentration (mg/mL).

For administration of Undiluted Treprostinil injection the rate is calculated using the following formula:

Undiluted Infusion Rate = Dose (ng/kg/min)     ×    Weight (kg)    ×    0.00006*                (mL/hour)                             Treprostinil Injection Vial Strength (mg/mL) *Conversion factor of 0.00006 = 60 min/hour × 0.000001 mg/ng For administration of Diluted Treprostinil injection, the concentration is calculated using the following formula:

Step 1 Diluted Treprostinil Injection    =   Dose (ng/kg/min)   x   Weight (kg)   x   0.00006                   Concentration                                           Infusion Rate (mL/hour)                    (mg/mL)

The volume of Treprostinil injection needed to make the required diluted Treprostinil injection concentration for the given reservoir size can then be calculated using the following formula:  Step 2   Volume of Treprostinil                Diluted Treprostinil                               Total Volume of Diluted Treprostinil        Injection (mL)          =     Injection Concentration (mg/mL)     x         Injection Solution in Reservoir (mL)                                           Treprostinil Injection Vial Strength                                                           (mg/mL) The calculated volume of Treprostinil injection is then added to the reservoir along with the sufficient volume of diluent to achieve the desired total volume in the reservoir.

Subcutaneous Infusion Treprostinil is administered subcutaneously by continuous infusion, via a subcutaneous catheter, using an infusion pump designed for subcutaneous drug delivery. The infusion pump should:(1) be adjustable to approximately 0.002 mL/hour, (2) have occlusion/no delivery, low battery, programming error and motor malfunction alarms, (3) have delivery accuracy of ±6% or better, (4) be positive pressure-driven, and (5) have a reservoir made of polyvinyl chloride, polypropylene or glass. Alternatively, use an infusion pump cleared for use with Treprostinil injection. To avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and subcutaneous infusion sets.

Intravenous Infusion External Intravenous Infusion Pump: Treprostinil injection is administered intravenously by continuous infusion via a surgically placed indwelling central venous catheter using an external infusion pump designed for intravenous drug delivery. If clinically necessary, a temporary peripheral intravenous cannula, preferably placed in a large vein, may be used for short term administration of Treprostinil injection. Use of a peripheral intravenous infusion for more than a few hours increases the risk of thrombophlebitis. The infusion pump used to administer Treprostinil injection should: (1) have occlusion/no delivery, low battery, programming error and motor malfunction alarms, (2) have delivery accuracy of ±6% or better, (3) be positive pressure driven, and (4) have a reservoir made of polyvinyl chloride, polypropylene or glass. Alternatively, use an infusion pump cleared for use with Treprostinil injection. To avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and infusion sets.

Infusion sets with an in-line 0.22- or 0.2-micron pore size filter should be used. Implantable Intravenous Infusion Pump: Use an implantable intravenous infusion pump approved for use with Treprostinil injection, such as the Implantable System for Treprostinil injection. Refer to the pump manufacturer’s manual for specific instructions regarding preparation, programing, implantation, and refilling.

Transition from epoprostenol to Treprostinil injection is accomplished by initiating the infusion of Treprostinil injection and increasing it, while simultaneously reducing the dose of intravenous epoprostenol. The transition to Treprostinil injection should take place in a hospital with constant observation of response (e.g., walk distance and signs and symptoms of disease progression). Initiate Treprostinil injection at a recommended dose of 10% of the current epoprostenol dose, and then escalate as the epoprostenol dose is decreased (see Table 2 for recommended dose titrations).

Patients are individually titrated to a dose that allows transition from epoprostenol therapy to Treprostinil injection while balancing prostacyclin-limiting adverse events. Treat increases in the patient's symptoms of PAH first with increases in the dose of Treprostinil injection. Treat side effects normally associated with prostacyclin and prostacyclin analogs first by decreasing the dose of epoprostenol.

Table 2: Recommended Transition Dose Changes

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="598.5"> <colgroup> <col width="11.1111111111111%"/> <col width="44.4444444444444%"/> <col width="44.4444444444444%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold"> Step</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Epoprostenol Dose</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Treprostinil Injection Dose</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">1<br/> </td><td align="center" class="Rrule" valign="middle">Unchanged<br/> </td><td align="center" class="Rrule" valign="middle">10% Starting Epoprostenol Dose<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">80% Starting Epoprostenol Dose<br/> </td><td align="center" class="Rrule" valign="middle">30% Starting Epoprostenol Dose<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">3<br/> </td><td align="center" class="Rrule" valign="middle">60% Starting Epoprostenol Dose<br/> </td><td align="center" class="Rrule" valign="middle">50% Starting Epoprostenol Dose<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">4<br/> </td><td align="center" class="Rrule" valign="middle">40% Starting Epoprostenol Dose<br/> </td><td align="center" class="Rrule" valign="middle">70% Starting Epoprostenol Dose<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">5<br/> </td><td align="center" class="Rrule" valign="middle">20% Starting Epoprostenol Dose<br/> </td><td align="center" class="Rrule" valign="middle">90% Starting Epoprostenol Dose<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">6<br/> </td><td align="center" class="Rrule" valign="middle">5% Starting Epoprostenol Dose<br/> </td><td align="center" class="Rrule" valign="middle">110% Starting Epoprostenol Dose<br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="middle">7<br/> </td><td align="center" class="Rrule" valign="middle">0<br/> </td><td class="Rrule" valign="middle">110% Starting Epoprostenol Dose + additional 5-10% increments as needed  </td> </tr> </tbody> </table></div>

20-mL vial containing 20 mg treprostinil (1 mg per mL).20-mL vial containing 50 mg treprostinil (2.5 mg per mL).20-mL vial containing 100 mg treprostinil (5 mg per mL).20-mL vial containing 200 mg treprostinil (10 mg per mL).

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None

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Chronic intravenous infusions of Treprostinil injection delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous infusion is the preferred mode of administration.  

In an open-label study of IV treprostinil (n=47) using an external infusion pump, there were seven catheter-related line infections during approximately 35 patient years, or about 1 BSI event per 5 years of use. A CDC survey of seven sites that used IV treprostinil for the treatment of PAH found approximately 1 BSI (defined as any positive blood culture) event per 3 years of use.  

Administration of IV Treprostinil injection with a high pH glycine diluent has been associated with a lower incidence of BSIs when compared to neutral diluents (sterile water, 0.9% sodium chloride) when used along with catheter care guidelines.

In an open-label study of an implantable pump (n=60), there were two blood stream infections (BSIs) related to the implant procedure during approximately 265 patient years.

Avoid abrupt withdrawal or sudden large reductions in dosage of Treprostinil injection, which may result in worsening of PAH symptoms.

Titrate slowly in patients with hepatic insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic function [see Dosage and Administration (2.5), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

Treprostinil is a pulmonary and systemic vasodilator. In patients with low systemic arterial pressure, treatment with Treprostinil injection may produce symptomatic hypotension.

Treprostinil injection inhibits platelet aggregation and increases the risk of bleeding.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Events with Subcutaneously Administered Treprostinil injection

Patients receiving Treprostinil injection as a subcutaneous infusion reported a wide range of adverse events, many potentially related to the underlying disease (dyspnea, fatigue, chest pain, right ventricular heart failure, and pallor). During clinical trials with subcutaneous infusion of Treprostinil injection, infusion site pain and reaction were the most common adverse events among those treated with Treprostinil injection. Infusion site reaction was defined as any local adverse event other than pain or bleeding/bruising at the infusion site and included symptoms such as erythema, induration, or rash. Infusion site reactions were sometimes severe and could lead to discontinuation of treatment. Table 3: Percentages of Subjects Reporting Subcutaneous Infusion Site Adverse Events

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="828.59"> <colgroup> <col width="35.7945425361156%"/> <col width="16.0513643659711%"/> <col width="16.0513643659711%"/> <col width="16.0513643659711%"/> <col width="16.0513643659711%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" rowspan="2" valign="middle"> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold"> Reaction</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Pain</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Treprostinil Injection</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Treprostinil Injection</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Severe<br/> </td><td align="center" class="Rrule" valign="middle">1<br/> </td><td align="center" class="Rrule" valign="middle">38<br/> </td><td align="center" class="Rrule" valign="middle">2<br/> </td><td align="center" class="Rrule" valign="middle">39<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Requiring narcotics<span class="Sup">a</span> <br/> </td><td align="center" class="Rrule" valign="middle">NA<span class="Sup">b</span> <br/> </td><td align="center" class="Rrule" valign="middle">NA<span class="Sup"> b</span> <br/> </td><td align="center" class="Rrule" valign="middle">1<br/> </td><td align="center" class="Rrule" valign="middle">32<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">Leading to discontinuation<br/> </td><td align="center" class="Rrule" valign="middle">0<br/> </td><td align="center" class="Rrule" valign="middle">3<br/> </td><td align="center" class="Rrule" valign="middle">0<br/> </td><td align="center" class="Rrule" valign="middle">7<br/> </td> </tr> </tbody> </table></div>

a  based on prescriptions for narcotics, not actual use

b  medications used to treat infusion site pain were not distinguished from those used to treat site reactions Other adverse events included diarrhea, jaw pain, edema, vasodilatation, and nausea, and these are generally considered to be related to the pharmacologic effects of Treprostinil injection, whether administered subcutaneously or intravenously. Adverse Reactions during Chronic Dosing

Table 4 lists adverse reactions that occurred at a rate of at least 3% more frequent in patients treated with subcutaneous Treprostinil injection than with placebo in controlled trials in PAH. Table 4: Adverse Reactions in Controlled 12-Week Studies of Subcutaneous Treprostinil Injection and at least 3% more frequent than on Placebo 

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="817.95"> <colgroup> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Adverse Reaction</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Treprostinil Injection</span> <br/> <span class="Bold">(N=236)</span> <br/> <span class="Bold">Percent of Patients</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(N=233)</span> <br/> <span class="Bold">Percent of Patients</span> <br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Infusion Site Pain<br/> </td><td align="center" class="Rrule" valign="middle">85<br/> </td><td align="center" class="Rrule" valign="middle">27<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Infusion Site Reaction<br/> </td><td align="center" class="Rrule" valign="middle">83<br/> </td><td align="center" class="Rrule" valign="middle">27<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Headache<br/> </td><td align="center" class="Rrule" valign="middle">27<br/> </td><td align="center" class="Rrule" valign="middle">23<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Diarrhea<br/> </td><td align="center" class="Rrule" valign="middle">25<br/> </td><td align="center" class="Rrule" valign="middle">16<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Nausea<br/> </td><td align="center" class="Rrule" valign="middle">22<br/> </td><td align="center" class="Rrule" valign="middle">18<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Rash<br/> </td><td align="center" class="Rrule" valign="middle">14<br/> </td><td align="center" class="Rrule" valign="middle">11<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Jaw Pain<br/> </td><td align="center" class="Rrule" valign="middle">13<br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td> </tr> <tr class="Botrule"> <td class="Lrule Rrule" valign="middle">Vasodilatation<br/> </td><td align="center" class="Rrule" valign="middle">11<br/> </td><td align="center" class="Rrule" valign="middle">5<br/> </td> </tr> <tr class="Last"> <td class="Lrule Rrule" valign="middle">Edema<br/> </td><td align="center" class="Rrule" valign="middle">9<br/> </td><td align="center" class="Rrule" valign="middle">3<br/> </td> </tr> </tbody> </table></div>

Reported adverse reactions (at least 3% more frequent on drug than on placebo) are included with the exception of those too general to be informative, and those not plausibly attributable to the use of the drug, because they were associated with the condition being treated or are very common in the treated population.

While hypotension occurred in both groups, the event was experienced twice as frequently in the

Treprostinil injection group as compared to the placebo group (4% in Treprostinil injection treatment group versus 2% in placebo-controlled group). As a potent vasodilator, hypotension is possible with the administration of Treprostinil injection.

The safety of Treprostinil injection was also studied in a long-term, open-label extension study in which 860 patients were dosed for a mean duration of 1.6 years, with a maximum exposure of 4.6 years. Twenty-nine (29%) percent achieved a dose of at least 40 ng/kg/min (max: 290 ng/kg/min). The safety profile during this chronic dosing study was similar to that observed in the 12-week placebo-controlled study except for the following suspected adverse drug reactions (occurring in at least 3% of patients): anorexia, vomiting, infusion site infection, asthenia, and abdominal pain.

Adverse Events Attributable to the Drug Delivery System

In controlled studies of Treprostinil injection administered subcutaneously, there were no reports of infection related to the drug delivery system. There were 187 infusion system complications reported in 28% of patients (23% Treprostinil injection, 33% placebo); 173 (93%) were pump related and 14 (7%) related to the infusion set. Eight of these patients (4 Treprostinil injection, 4 placebo) reported non-serious adverse events resulting from infusion system complications. Adverse events resulting from problems with the delivery systems were typically related to either symptoms of excess Treprostinil injection (e.g., nausea) or return of PAH symptoms (e.g., dyspnea). These events were generally resolved by correcting the delivery system pump or infusion set problem, such as replacing the syringe or battery, reprogramming the pump, or straightening a crimped infusion line. Adverse events resulting from problems with the delivery system did not lead to clinical instability or rapid deterioration. In addition to these adverse events due to the drug delivery system during subcutaneous administration, the following adverse events may be attributable to the IV mode of infusion including arm swelling, paresthesia, hematoma, and pain [see Warnings and Precautions (5.1)].

In addition to adverse reactions reported from clinical trials, the following events have been identified during post-approval use of Treprostinil injection. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The following events have been chosen for inclusion because of a combination of their seriousness, frequency of reporting, and potential connection to Treprostinil injection. These events are thrombophlebitis associated with peripheral intravenous infusion, thrombocytopenia, bone pain, pruritus, dizziness, arthralgia, myalgia/muscle spasm, and pain in extremity. In addition, generalized rashes, sometimes macular or papular in nature, and cellulitis have been infrequently reported.

Dose adjustment of treprostinil may be necessary when co-administered with CYP2C8 inducers or inhibitors. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to treprostinil. It has not been determined if the changes in exposure of treprostinil with inhibitors or inducers of CYP2C8 observed for the oral administration of treprostinil would be similar for treprostinil administered via the parenteral route [see Clinical Pharmacology (12.3)].

Risk Summary Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug- associated risk of adverse developmental outcomes. However, there are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations). In animal studies, no adverse reproductive and developmental effects were seen in rats at about 123 and 48 times the human exposure based on Cmax and AUC, respectively. In rabbits, external fetal and soft tissue malformations and skeletal malformations were observed at about 7 and 5 times the human exposure based on Cmax and AUC, respectively (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. Data Animal reproduction studies have been conducted with treprostinil via continuous subcutaneous administration and with treprostinil diolamine administered orally. In pregnant rats, continuous subcutaneous infusions of treprostinil during organogenesis and late gestational development, at doses as high as 900 ng treprostinil/kg/min (about 117 times the starting human subcutaneous infusion rate, on a ng/m2 basis and about 16 times the average rate achieved in clinical trials), resulted in no evidence of harm to the fetus. In pregnant rabbits, effects of continuous subcutaneous infusions of treprostinil during organogenesis were limited to an increased incidence of fetal skeletal variations (bilateral full rib or right rudimentary rib on lumbar 1) associated with maternal toxicity (reduction in body weight and food consumption) at a dose of 150 ng treprostinil/kg/min (about 41 times the starting human subcutaneous infusion rate, on a ng/m2 basis, and 5 times the average rate used in clinical trials). In rats, continuous subcutaneous infusion of treprostinil from implantation to the end of lactation, at doses of up to 450 ng treprostinil/kg/min, did not affect the growth and development of offspring. In studies with orally administered treprostinil diolamine, no adverse effect doses for fetal viability/growth, fetal development (teratogenicity), and postnatal development were determined in rats. In pregnant rats, no evidence of harm to the fetus was observed following oral administration of treprostinil diolamine at the highest dose tested (20 mg/kg/day), which represents about 123 and 48 times the human exposure, when based on Cmax and AUC of the average subcutaneous infusion rate achieved in clinical trials, respectively. In pregnant rabbits, external fetal and soft tissue malformations and fetal skeletal malformation occurred. The dose at which no adverse effects were seen (0.5 mg/kg/day) represents about 7 and 5 times the human exposure, when based on Cmax and AUC of the average subcutaneous infusion rate achieved in clinical trials, respectively. No treprostinil treatment-related effects on labor and delivery were seen in animal studies.Animal reproduction studies are not always predictive of human response.

Risk Summary There are no data on the presence of treprostinil in human milk, the effects on the  breastfed infant, or the effects on milk production.

Safety and effectiveness in pediatric patients have not been established. Clinical studies of Treprostinil injection did not include sufficient numbers of patients aged ≤16 years to determine whether they respond differently from older patients.

Clinical studies of Treprostinil injection did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Treprostinil injection clearance is reduced in patients with hepatic insufficiency. In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Treprostinil injection to 0.625 ng/kg/min ideal body weight, and monitor closely. Treprostinil injection has not been studied in patients with severe hepatic insufficiency [see Dosage and Administration (2.5), Warnings and Precautions (5.3), and Clinical Pharmacology (12.3)].

No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis [see Clinical Pharmacology (12.3)].

Signs and symptoms of overdose with Treprostinil injection during clinical trials are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of Treprostinil injection. In controlled clinical trials using an external infusion pump, seven patients received some level of overdose and in open-label follow-on treatment seven additional patients received an overdose; these occurrences resulted from accidental bolus administration of Treprostinil injection, errors in pump programmed rate of administration, and prescription of an incorrect dose. In only two cases did excess delivery of Treprostinil injection produce an event of substantial hemodynamic concern (hypotension, near-syncope). One pediatric patient was accidentally administered 7.5 mg of Treprostinil injection via a central venous catheter. Symptoms included flushing, headache, nausea, vomiting, hypotension, and seizure-like activity with loss of consciousness lasting several minutes. The patient subsequently recovered.

{ "type": "p", "children": [], "text": "Signs and symptoms of overdose with Treprostinil injection during clinical trials are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of Treprostinil injection.\nIn controlled clinical trials using an external infusion pump, seven patients received some level of overdose and in open-label follow-on treatment seven additional patients received an overdose; these occurrences resulted from accidental bolus administration of Treprostinil injection, errors in pump programmed rate of administration, and prescription of an incorrect dose. In only two cases did excess delivery of Treprostinil injection produce an event of substantial hemodynamic concern (hypotension, near-syncope).\nOne pediatric patient was accidentally administered 7.5 mg of Treprostinil injection via a central venous catheter. Symptoms included flushing, headache, nausea, vomiting, hypotension, and seizure-like activity with loss of consciousness lasting several minutes. The patient subsequently recovered." }

Treprostinil injection is a sterile solution of treprostinil, a prostacyclin mimetic, formulated  for subcutaneous or intravenous administration. Treprostinil injection is supplied in 20-mL multi-dose vials in four strengths, containing 20 mg, 50 mg, 100 mg, or 200 mg (1 mg/mL, 2.5 mg/mL, 5 mg/mL or 10 mg/mL) of treprostinil. Each mL also contains 5.3 mg sodium chloride (except for the 10 mg/mL strength which contain 4.0 mg sodium chloride), 3 mg metacresol, 6.3 mg sodium citrate dihydrate, and water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust pH between 6.0 and 7.2. Treprostinil is chemically stable at room temperature and neutral pH. Treprostinil is (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1-Hbenz[f]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C23H34O5. The structural formula of treprostinil is:

{ "type": "p", "children": [], "text": "Treprostinil injection is a sterile solution of treprostinil, a prostacyclin mimetic, formulated  for subcutaneous or intravenous administration. Treprostinil injection is supplied in 20-mL multi-dose vials in four strengths, containing 20 mg, 50 mg, 100 mg, or 200 mg (1 mg/mL, 2.5 mg/mL, 5 mg/mL or 10 mg/mL) of treprostinil. Each mL also contains 5.3 mg sodium chloride (except for the 10 mg/mL strength which contain 4.0 mg sodium chloride), 3 mg metacresol, 6.3 mg sodium citrate dihydrate, and water for injection. Sodium hydroxide and hydrochloric acid may be added to adjust pH between 6.0 and 7.2.\nTreprostinil is chemically stable at room temperature and neutral pH.\nTreprostinil is (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1-Hbenz[f]inden-5-yl]oxy]acetic acid. Treprostinil has a molecular weight of 390.52 and a molecular formula of C23H34O5. \n The structural formula of treprostinil is:" }

The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds, and inhibition of platelet aggregation.

In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. Other studies have shown that treprostinil causes a dose-related negative inotropic and lusitropic effect. No major effects on cardiac conduction have been observed. Treprostinil produces vasodilation and tachycardia. Single doses of treprostinil up to 84 mcg by inhalation produce modest and short-lasting effects on QTc, but this is apt to be an artifact of the rapidly changing heart rate. Treprostinil administered by the subcutaneous or intravenous routes has the potential to generate concentrations many-fold greater than those generated via the inhaled route; the effect on the QTc interval when treprostinil is administered parenterally has not been established.

The pharmacokinetics of continuous subcutaneous Treprostinil injection are linear over the dose range of 2.5 to 125 ng/kg/min (corresponding to plasma concentrations of about 260 pg/mL to 18,250 pg/mL) and can be described by a two-compartment model. Dose proportionality at infusion rates greater than 125 ng/kg/min has not been studied. Subcutaneous and intravenous administration of Treprostinil injection demonstrated bioequivalence at steady state at a dose of 10 ng/kg/min.

Absorption Treprostinil injection is relatively rapidly and completely absorbed after subcutaneous infusion, with an absolute bioavailability approximating 100%. Steady-state concentrations occurred in approximately 10 hours. Concentrations in patients treated with an average dose of 9.3 ng/kg/min were approximately 2,000 ng/L. Distribution The volume of distribution of the drug in the central compartment is approximately 14 L/70 kg ideal body weight. Treprostinil injection at in vitro concentrations well above what is clinically relevant was 91% bound to human plasma protein. Metabolism and Excretion Treprostinil is substantially metabolized by the liver, primarily by CYP2C8. In a study conducted in healthy volunteers using [14C] treprostinil, 79% and 13% of the subcutaneous dose was recovered in the urine and feces, respectively, over 10 days. Only 4% was excreted as unchanged treprostinil in the urine. Five metabolites were detected in the urine, ranging from 10% to 16% and representing 64% of the dose administered. Four of the metabolites are products of oxidation of the 3- hydroxyloctyl side chain and one is a glucuroconjugated derivative (treprostinil glucuronide). The identified metabolites do not appear to have activity. The elimination of treprostinil (following subcutaneous administration) is biphasic, with a terminal elimination half-life of approximately 4 hours using a two compartment model. Systemic clearance is approximately 30 L/hour for a 70 kg person. Based on in vitro studies treprostinil does not inhibit or induce major CYP enzymes.  Specific Populations Hepatic Insufficiency In patients with portopulmonary hypertension and mild (n=4) or moderate (n=5) hepatic insufficiency, Treprostinil injection at a subcutaneous dose of 10 ng/kg/min for 150 minutes had a Cmax that was 2-fold and 4-fold, respectively, and an AUC0-∞ that was 3-fold and 5-fold, respectively, values observed in healthy subjects. Clearance in patients with hepatic insufficiency was reduced by up to 80% compared to healthy adults. Renal Impairment In patients with severe renal impairment requiring dialysis (n=8), administration of a single 1 mg dose of orally administered treprostinil pre-and post-dialysis resulted in an AUC0-inf that was not significantly altered compared to healthy subjects.

Drug Interaction Studies

Effect of CYP2C8 Inhibitors and Inducers on Treprostinil

Co-administration of an oral formulation of treprostinil (treprostinil diolamine) with gemfibrozil (600 mg twice a day), a CYP2C8 enzyme inhibitor, doubles the AUC and Cmax of treprostinil in healthy adults. Co-administration of an oral formulation of treprostinil (treprostinil diolamine) with rifampin (600 mg/day), a CYP2C8 enzyme inducer, decreases AUC of treprostinil by 22%.

Effect of Treprostinil on Cytochrome P450 Enzymes

In vitro studies of human hepatic microsomes showed that treprostinil does not inhibit cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A. Additionally, treprostinil does not induce CYP1A2, CYP2B6, CYP2C9, CYP2C19, and CYP3A isoenzymes.

Effect of Other Drugs on Treprostinil

Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both Cmax and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to treprostinil.

Drug interaction studies have been carried out with treprostinil (oral or subcutaneous) co-administered with acetaminophen (4 g/day), esomeprazole (40 mg/day), bosentan (250 mg/day), sildenafil (60 mg/day), warfarin (25 mg/day), and fluconazole (200 mg/day), respectively, in healthy volunteers. These studies did not show a clinically significant effect on the pharmacokinetics of treprostinil. Treprostinil does not affect the pharmacokinetics or pharmacodynamics of warfarin. The pharmacokinetics of R-and S-warfarin and the INR in healthy subjects given a single 25 mg dose of warfarin were unaffected by continuous subcutaneous infusion of treprostinil at an infusion rate of 10 ng/kg/min. 

A two-year rat carcinogenicity study was performed with treprostinil inhalation at target doses of 5.26, 10.6, and 34.1 mcg/kg/day. There was no evidence for carcinogenic potential associated with treprostinil inhalation in rats at systemic exposure levels up to about 34 and 1 times the human exposure, when based on Cmax and AUC of the average subcutaneous infusion rate achieved in clinical trials, respectively. In vitro and in vivo genetic toxicology studies did not demonstrate any mutagenic or clastogenic effects of treprostinil. Treprostinil sodium did not affect fertility or mating performance of male or female rats given continuous subcutaneous (sc) infusions at rates of up to 450 ng treprostinil/kg/min [about 59 times the recommended starting human sc infusion rate (1.25 ng/kg/min) and 8 times the average rate (9.3 ng/kg/min) achieved in clinical trials, on a ng/m2 basis]. In this study, males were dosed from 10 weeks prior to mating and through the 2-week mating period. Females were dosed from 2 weeks prior to mating until gestational day 6.

Treprostinil diolamine did not demonstrate any carcinogenic effects in mouse or rat carcinogenicity studies. Oral administration of treprostinil diolamine to Tg.rasH2 mice at 0, 5, 10, and 20 mg/kg/day in males and 0, 3, 7.5, and 15 mg/kg/day in females daily for 26 weeks did not significantly increase the incidence of tumors. The exposures, when based on AUC, obtained at the highest dose levels used in males and females are about 7-and 15-fold, respectively, the human exposure of the average subcutaneous infusion rate achieved in clinical trials. Oral administration of treprostinil diolamine to Sprague Dawley rats at 0, 1, 3, and 10 mg/kg/day daily for 104 weeks did not significantly increase the incidence of tumors. The exposures obtained at the highest dose levels used in males and females are about 18-and 26-fold, respectively, the human exposure of the average subcutaneous infusion rate achieved in clinical trials.

Treprostinil diolamine was tested in vivo in a rat micronucleus assay and did not induce an increased incidence of micronucleated polychromatic erythrocytes.

Two 12-week, multicenter, randomized, double-blind studies compared continuous subcutaneous infusion of Treprostinil injection to placebo in a total of 470 patients with NYHA Class II (11%), III (81%), or IV (7%) PAH. PAH was idiopathic/heritable in 58% of patients, associated with connective tissue diseases in 19%, and the result of congenital systemic-to-pulmonary shunts in 23%. The mean age was 45 (range 9 to 75 years). About 81% were female and 84% were Caucasian. Pulmonary hypertension had been diagnosed for a mean of 3.8 years. The primary endpoint of the studies was change in 6-minute walking distance, a standard measure of exercise capacity. There were many assessments of symptoms related to heart failure, but local discomfort and pain associated with Treprostinil injection may have substantially unblinded those assessments. The 6-minute walking distance and an associated subjective measurement of shortness of breath during the walk (Borg dyspnea score) were administered by a person not participating in other aspects of the study. Treprostinil injection was administered as a subcutaneous infusion, described in Section 2, DOSAGE AND ADMINISTRATION, and the dose averaged 9.3 ng/kg/min at Week 12. Few subjects received doses greater than 40 ng/kg/min. Background therapy, determined by the investigators, could include anticoagulants, oral vasodilators, diuretics, digoxin, and oxygen, but not an endothelin receptor antagonist or epoprostenol. The two studies were identical in design and conducted simultaneously, and the results were analyzed both pooled and individually. Hemodynamic Effects As shown in Table 5, chronic therapy with Treprostinil injection resulted in small hemodynamic changes consistent with pulmonary and systemic vasodilation. Table 5: Hemodynamics during Chronic Administration of Treprostinil Injection in Patients with PAH in 12-Week Studies

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="1123.85"> <colgroup> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> <col width="20%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" rowspan="2" valign="middle"><span class="Bold">Hemodynamic</span> <br/> <span class="Bold">Parameter</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Baseline</span> <br/> </td><td align="center" class="Rrule" colspan="2" valign="middle"><span class="Bold">Mean change from baseline at Week 12</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Treprostinil injection</span> <br/> <span class="Bold">(N=204-231)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(N=215-235)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Treprostinil injection</span> <br/> <span class="Bold">(N=163-199)</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Placebo</span> <br/> <span class="Bold">(N=182-215)</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">CI (L/min/m<span class="Sup">2</span> )<br/> </td><td align="center" class="Rrule" valign="middle">2.4 ± 0.88<br/> </td><td align="center" class="Rrule" valign="middle">2.2 ± 0.74<br/> </td><td align="center" class="Rrule" valign="middle">+0.12 ± 0.58*<br/> </td><td align="center" class="Rrule" valign="middle">-0.06 ± 0.55<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">PAPm (mmHg)<br/> </td><td align="center" class="Rrule" valign="middle">62 ± 17.6<br/> </td><td align="center" class="Rrule" valign="middle">60 ± 14.8<br/> </td><td align="center" class="Rrule" valign="middle">-2.3 ± 7.3*<br/> </td><td align="center" class="Rrule" valign="middle">+0.7 ± 8.5<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">RAPm (mmHg)<br/> </td><td align="center" class="Rrule" valign="middle">10 ± 5.7<br/> </td><td align="center" class="Rrule" valign="middle">10 ± 5.9<br/> </td><td align="center" class="Rrule" valign="middle">-0.5 ± 5.0*<br/> </td><td align="center" class="Rrule" valign="middle">+1.4 ± 4.8<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">PVRI (mmHg/L/min/m<span class="Sup">2 </span>)<br/> </td><td align="center" class="Rrule" valign="middle">26 ± 13<br/> </td><td align="center" class="Rrule" valign="middle">25 ± 13<br/> </td><td align="center" class="Rrule" valign="middle">-3.5 ± 8.2*<br/> </td><td align="center" class="Rrule" valign="middle">+1.2 ± 7.9<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">SVRI (mmHg/L/min/m<span class="Sup">2</span> )<br/> </td><td align="center" class="Rrule" valign="middle">38 ± 15<br/> </td><td align="center" class="Rrule" valign="middle">39 ± 15<br/> </td><td align="center" class="Rrule" valign="middle">-3.5 ± 12*<br/> </td><td align="center" class="Rrule" valign="middle">-0.80 ± 12<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">SvO<span class="Sub">2 </span>(%)<br/> </td><td align="center" class="Rrule" valign="middle">62 ± 100<br/> </td><td align="center" class="Rrule" valign="middle">60 ± 11<br/> </td><td align="center" class="Rrule" valign="middle">+2.0 ± 10*<br/> </td><td align="center" class="Rrule" valign="middle">-1.4 ± 8.8<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">SAPm (mmHg)<br/> </td><td align="center" class="Rrule" valign="middle">90 ± 14<br/> </td><td align="center" class="Rrule" valign="middle">91 ± 14<br/> </td><td align="center" class="Rrule" valign="middle">-1.7 ± 12<br/> </td><td align="center" class="Rrule" valign="middle">-1.0 ± 13<br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="middle">HR (bpm)<br/> </td><td align="center" class="Rrule" valign="middle">82 ± 13<br/> </td><td align="center" class="Rrule" valign="middle">82 ± 15<br/> </td><td align="center" class="Rrule" valign="middle">-0.5 ± 11<br/> </td><td align="center" class="Rrule" valign="middle">-0.8 ± 11<br/> </td> </tr> </tbody> </table></div>

*  Denotes statistically significant difference between Treprostinil injection and placebo, p<0.05.

CI = cardiac index; PAPm = mean pulmonary arterial pressure; PVRI = pulmonary vascular resistance indexed; RAPm = mean right atrial pressure; SAPm = mean systemic arterial pressure; SVRI = systemic vascular resistance indexed; SvO2 = mixed venous oxygen saturation; HR = heart rate.

 Clinical Effects The effect of Treprostinil injection on 6-minute walk, the primary end point of the 12-week studies, was small and did not achieve conventional levels of statistical significance. For the combined populations, the median change from baseline on Treprostinil Injection was 10 meters and the median change from baseline on placebo was 0 meters from a baseline of approximately 345 meters. Although it was not the primary endpoint of the study, the Borg dyspnea score was significantly improved by Treprostinil injection during the 6-minute walk, and Treprostinil injection also had a significant effect, compared with placebo, on an assessment that combined walking distance with the Borg dyspnea score. Treprostinil injection also consistently improved indices of dyspnea, fatigue, and signs and symptoms of pulmonary hypertension, but these indices were difficult to interpret in the context of incomplete blinding to treatment assignment resulting from infusion site symptoms.

In an 8-week, multicenter, randomized, double-blind, placebo-controlled study, patients on stable doses of Flolan were randomly withdrawn from Flolan to placebo or Treprostinil injection. Fourteen Treprostinil injection and 8 placebo patients completed the study. The primary endpoint of the study was the time to clinical deterioration, defined as either an increase in Flolan dose, hospitalization due to PAH, or death. No patients died during the study. During the study period, Treprostinil injection effectively prevented clinical deterioration in patients transitioning from Flolan therapy compared to placebo (Figure 1). Thirteen of 14 patients in the Treprostinil injection arm were able to transition from Flolan successfully, compared to only 1 of 8 patients in the placebo arm (p=0.0002). Figure 1: Time to Clinical Deterioration for PAH Patients Transitioned from Flolan to Treprostinil Injection or Placebo in an 8-Week Study

Treprostinil injection is supplied in 20-mL multi-dose vials as sterile solutions in water for injection, individually packaged in cartons. Unopened vials of Treprostinil injection are stable until the date indicated when stored at 25°C (77°F), with excursions permitted to 2-30°C (36-86°F). A single vial of Treprostinil injection should be used for no more than 30 days after the initial introduction into the vial. Treprostinil injection is supplied as:

{ "type": "p", "children": [], "text": "Treprostinil injection is supplied in 20-mL multi-dose vials as sterile solutions in water for injection, individually packaged in cartons. Unopened vials of Treprostinil injection are stable until the date indicated when stored at 25°C (77°F), with excursions permitted to 2-30°C (36-86°F). A single vial of Treprostinil injection should be used for no more than 30 days after the initial introduction into the vial.\nTreprostinil injection is supplied as:" }

<div class="scrollingtable"><table border="0" cellpadding="0" cellspacing="0" width="817.95"> <colgroup> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> <col width="33.3333333333333%"/> </colgroup> <tbody class="Headless"> <tr class="Botrule First"> <td align="center" class="Lrule Rrule" valign="middle"><span class="Bold">Treprostinil Injection</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">Concentration</span> <br/> </td><td align="center" class="Rrule" valign="middle"><span class="Bold">NDC</span> <br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">20 mg / 20 mL<br/> </td><td align="center" class="Rrule" valign="middle">1 mg/ mL<br/> </td><td align="center" class="Rrule" valign="middle">62332-514-20<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">50 mg / 20 mL<br/> </td><td align="center" class="Rrule" valign="middle">2.5 mg/ mL<br/> </td><td align="center" class="Rrule" valign="middle">62332-515-20<br/> </td> </tr> <tr class="Botrule"> <td align="center" class="Lrule Rrule" valign="middle">100 mg / 20 mL<br/> </td><td align="center" class="Rrule" valign="middle">5 mg/ mL<br/> </td><td align="center" class="Rrule" valign="middle">62332-516-20<br/> </td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule" valign="middle">200 mg / 20 mL<br/> </td><td align="center" class="Rrule" valign="middle">10 mg/ mL<br/> </td><td align="center" class="Rrule" valign="middle">62332-517-20<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"817.95\">\n<colgroup>\n<col width=\"33.3333333333333%\"/>\n<col width=\"33.3333333333333%\"/>\n<col width=\"33.3333333333333%\"/>\n</colgroup>\n<tbody class=\"Headless\">\n<tr class=\"Botrule First\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"middle\"><span class=\"Bold\">Treprostinil Injection</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">Concentration</span>\n<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\"><span class=\"Bold\">NDC</span>\n<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"middle\">20 mg / 20 mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">1 mg/ mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">62332-514-20<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"middle\">50 mg / 20 mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">2.5 mg/ mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">62332-515-20<br/>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"middle\">100 mg / 20 mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">5 mg/ mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">62332-516-20<br/>\n</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Lrule Rrule\" valign=\"middle\">200 mg / 20 mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">10 mg/ mL<br/>\n</td><td align=\"center\" class=\"Rrule\" valign=\"middle\">62332-517-20<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

Interruption of Therapy Advise patients and caregivers to seek medical attention if they experience signs or symptoms of abrupt withdrawal of therapy or suspect a pump malfunction [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "\nInterruption of Therapy\nAdvise patients and caregivers to seek medical attention if they experience signs or symptoms of abrupt withdrawal of therapy or suspect a pump malfunction [see Warnings and Precautions (5.2)].\n" }

Overdose Inform patients and their caregivers to seek medical attention if they experience signs or symptoms of Treprostinil injection overdose [see Overdosage (10)].

{ "type": "p", "children": [], "text": "\n Overdose\nInform patients and their caregivers to seek medical attention if they experience signs or symptoms of Treprostinil injection overdose [see Overdosage (10)].\n" }

Manufactured for: Alembic Pharmaceuticals, Inc. Bedminster, NJ 07921, USA Manufactured by: Corden Pharma S.p.A. Viale dell’Industria, 3 20867 Caponago (MB) Italy Revised: 12/2024

{ "type": "p", "children": [], "text": "\nManufactured for:\n Alembic Pharmaceuticals, Inc. Bedminster, NJ 07921, USA\n\n Manufactured by:\n Corden Pharma S.p.A. Viale dell’Industria, 3 20867 Caponago (MB) Italy\n Revised: 12/2024\n\n\n" }

Treprostinil injection, 20 mg/20 mL - 20 mL MDV Label 

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 20 mg/20 mL - 20 mL MDV Label \n" }

Treprostinil injection, 20 mg/20 mL - 20 mL MDV Carton

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 20 mg/20 mL - 20 mL MDV Carton\n" }

Treprostinil injection, 50 mg/20 mL - 20 mL MDV Label

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 50 mg/20 mL - 20 mL MDV Label\n" }

Treprostinil injection, 50 mg/20 mL - 20 mL MDV Carton

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 50 mg/20 mL - 20 mL MDV Carton\n" }

Treprostinil injection, 100 mg/20 mL - 20 mL MDV Label

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 100 mg/20 mL - 20 mL MDV Label\n" }

Treprostinil injection, 100 mg/20 mL - 20 mL MDV Carton

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 100 mg/20 mL - 20 mL MDV Carton\n" }

Treprostinil injection, 200 mg/20 mL - 20 mL MDV Label

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 200 mg/20 mL - 20 mL MDV Label\n" }

Treprostinil injection, 200 mg/20 mL - 20 mL MDV Carton

{ "type": "p", "children": [], "text": "\nTreprostinil injection, 200 mg/20 mL - 20 mL MDV Carton\n" }