Tobramycin inhalation solution, USP is indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa.

{ "type": "p", "children": [], "text": "\nTobramycin inhalation solution, USP is indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with Pseudomonas aeruginosa." }

Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV1) <25% or >75% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14)].

{ "type": "p", "children": [], "text": "Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV1) <25% or >75% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14)].\n" }

Tobramycin inhalation solution, USP is for oral inhalation only [see Dosage and Administration (2.2)]. The recommended dosage of tobramycin inhalation solution for both adults and pediatric patients 6 years of age and older is one single-dose ampule (300 mg) administered twice daily for 28 days. Dosage is not adjusted by weight. All patients should be administered 300 mg twice daily.

Tobramycin inhalation solution, USP is administered twice daily in alternating periods of 28 days. After 28 days of therapy, patients should stop tobramycin inhalation solution therapy for the next 28 days, and then resume therapy for the next 28 day on/28 day off cycle. The doses should be taken as close to 12 hours apart as possible; they should not be taken less than 6 hours apart.

If patients miss a dose, they should take it as soon as possible anytime up to 6 hours prior to their next scheduled dose. If less than 6 hours remain before the next dose, wait until their next scheduled dose.

Tobramycin inhalation solution, USP is administered by oral inhalation over an approximately 15-minute period, using a hand-held PARI LC PLUSTM Reusable Nebulizer with a DeVilbiss® Pulmo-Aide® compressor. Tobramycin inhalation solution should not be diluted or mixed with dornase alfa or other medications in the nebulizer. Tobramycin inhalation solution, USP is not for subcutaneous, intravenous or intrathecal administration.

Prior to administration of tobramycin inhalation solution, read the Patient Information/Instructions for Use for tobramycin inhalation solution for detailed information on how to use tobramycin inhalation solution and follow the manufacturer's instructions for use and care of the PARI LC PLUSTM Reusable Nebulizer and DeVilbiss® Pulmo-Aide® air compressor. Tobramycin inhalation solution, USP is inhaled while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help the patient breathe through the mouth.

Instruct patients on multiple therapies to take their medications, prior to inhaling tobramycin inhalation solution or as directed by their physician.

Tobramycin inhalation solution, USP should not be used if it is cloudy, if there are particles in the solution, or if it has been stored at room temperature for more than 28 days.

Tobramycin inhalation solution is supplied as a sterile inhalational solution for nebulization in single-dose 5 mL ampules. Each 5 mL ampule contains 300 mg of tobramycin.

{ "type": "p", "children": [], "text": "\nTobramycin inhalation solution is supplied as a sterile inhalational solution for nebulization in single-dose 5 mL ampules. Each 5 mL ampule contains 300 mg of tobramycin." }

Tobramycin inhalation solution is contraindicated in patients with a known hypersensitivity to any aminoglycoside.

{ "type": "p", "children": [], "text": "\nTobramycin inhalation solution is contraindicated in patients with a known hypersensitivity to any aminoglycoside." }

Bronchospasm can occur with inhalation of tobramycin inhalation solution. In clinical studies with tobramycin inhalation solution, changes in FEV1 measured after the inhaled dose were similar in tobramycin inhalation solution and placebo groups. Bronchospasm that occurs during the use of tobramycin inhalation solution should be treated as medically appropriate.

Ototoxicity with use of Tobramycin inhalation solution

Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides.

Transient tinnitus occurred in eight tobramycin inhalation solution treated patients versus no placebo patients in the clinical studies. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants further clinical investigation.

Ototoxicity, as measured by complaints of hearing loss or by audiometric evaluations, did not occur with tobramycin inhalation solution therapy during clinical studies, however in postmarketing experience, patients receiving tobramycin inhalation solution have reported hearing loss.

Vestibular toxicity may be manifested by vertigo, ataxia or dizziness. Patients with known or suspected auditory or vestibular dysfunction should be closely monitored when taking tobramycin inhalation solution. Monitoring might include obtaining audiometric evaluations and serum tobramycin levels. If ototoxicity is noted, the patient should be managed as medically appropriate, including potentially discontinuing tobramycin inhalation solution.

Risk of Ototoxicity Due to Mitochondrial DNA Variants

Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant. Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. Mitochondrial DNA variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies.

Nephrotoxicity was not seen during clinical studies with tobramycin inhalation solution but has been associated with aminoglycosides as a class. Patients with known or suspected renal dysfunction or taking concomitant nephrotoxic drugs along with tobramycin inhalation solution should have serum concentrations of tobramycin and laboratory measurements of renal function obtained at the discretion of the treating physician. If nephrotoxicity develops, the patient should be managed as medically appropriate, including potentially discontinuing tobramycin inhalation solution.

Aminoglycosides, including tobramycin, may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function. Neuromuscular blockade, respiratory failure, and prolonged respiratory paralysis may occur more commonly in patients with underlying neuromuscular disorders, such as myasthenia gravis or Parkinson's disease.

Prolonged respiratory paralysis may also occur in patients receiving concomitant neuromuscular blocking agents. If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical assistance may be necessary.

Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. Patients who use tobramycin inhalation solution during pregnancy, or become pregnant while taking tobramycin inhalation solution should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

Patients receiving concomitant tobramycin inhalation solution and parenteral aminoglycoside therapy should be monitored as clinically appropriate for toxicities associated with aminoglycosides as a class. Serum tobramycin levels should be monitored.

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.

Tobramycin inhalation solution was studied in two Phase 3 clinical studies involving 258 cystic fibrosis patients ranging in age from 6 to 48 years. Patients received tobramycin inhalation solution in alternating periods of 28 days on and 28 days off drug in addition to their standard cystic fibrosis therapy for a total of 24 weeks.

Table 1 lists the percent of patients with selected adverse reactions that occurred in >5% of tobramycin inhalation solution patients during the two Phase 3 studies.

<div class="scrollingtable"><table class="Noautorules" width="638"> <caption> <span> Table 1: Percent of Patients With Selected Adverse Reactions Occurring in &gt;5% of Tobramycin Inhalation Solution Patients </span> </caption> <col width="373"/> <col width="162"/> <col width="103"/> <tbody class="Headless"> <tr> <td align="left" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> Adverse Reaction</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Tobramycin</span> <br/> <span class="Bold"> Inhalation Solution</span> <br/> <span class="Bold"> (n=258)</span> <br/> <span class="Bold"> %</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> Placebo</span> <br/> <span class="Bold"> (n=262)</span> <br/> <span class="Bold"> %</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Cough Increased<br/> Pharyngitis<br/> Sputum Increased<br/> Dyspnea<br/> Hemoptysis<br/> Lung Function Decreased<span class="Sup">1</span> <br/> Voice Alteration<br/> Taste Perversion<br/> Rash<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 46.1<br/> 38.0<br/> 37.6<br/> 33.7<br/> 19.4<br/> 16.3<br/> 12.8<br/> 6.6<br/> 5.4<br/> </td><td align="center" class="Botrule Rrule" valign="top"> 47.3<br/> 39.3<br/> 39.7<br/> 38.5<br/> 23.7<br/> 15.3<br/> 6.5<br/> 6.9<br/> 6.1<br/> </td> </tr> </tbody> </table></div>

Includes reported decreases in pulmonary function tests or decreased lung volume on chest radiograph associated with intercurrent illness or study drug administration.

Selected adverse reactions that occurred in less than or equal to 5% of patients treated with tobramycin inhalation solution:

Ear and Labyrinth Disorders: Tinnitus

Musculoskeletal and Connective Tissue Disorders: Myalgia

Infections and Infestations: Laryngitis

Voice Alteration and Tinnitus

Voice alteration and tinnitus were the only adverse reactions reported by significantly more tobramycin inhalation solution-treated patients. Thirty- three patients (13%) treated with tobramycin inhalation solution complained of voice alteration compared to 17 (7%) placebo patients. Voice alteration was more common in the on-drug periods.

Eight patients from the tobramycin inhalation solution group (3%) reported tinnitus compared to no placebo patients. All episodes were transient, resolved without discontinuation of the tobramycin inhalation solution treatment regimen, and were not associated with loss of hearing in audiograms. Tinnitus is one of the sentinel symptoms of cochlear toxicity, and patients with this symptom should be carefully monitored for high frequency hearing loss. The numbers of patients reporting vestibular adverse experiences such as dizziness were similar in the tobramycin inhalation solution and placebo groups.

Changes in Serum Creatinine

Nine (3%) patients in the tobramycin inhalation solution group and nine (3%) patients in the placebo group had increases in serum creatinine of at least 50% over baseline. In all nine patients in the tobramycin inhalation solution group, creatinine decreased at the next visit.

The following adverse reactions have been identified during post-approval use of tobramycin inhalation solution. 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.

Ear and Labyrinth Disorders

Hearing loss: Some of these reports occurred in patients with previous or concomitant treatment with systemic aminoglycosides. Patients with hearing loss frequently reported tinnitus [see Warnings and Precautions (5.2)].

Skin and Subcutaneous Tissue Disorders

Hypersensitivity, pruritus, urticaria, rash

Nervous System Disorders

Aphonia, dysgeusia

Respiratory, Thoracic, and Mediastinal Disorders

Bronchospasm [see Warnings and Precautions (5.1)] oropharyngeal pain

Metabolism and Nutrition Disorders

Decreased appetite

Concurrent and/or sequential use of tobramycin inhalation solution with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided.

Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Tobramycin inhalation solution should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and tobramycin inhalation solution has not been evaluated.

Risk Summary

Aminoglycosides can cause fetal harm. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [see Warnings and Precautions (5.5)]. Although there are no available data on tobramycin inhalation solution use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. There are risks to the mother associated with cystic fibrosis in pregnancy (see Clinical Considerations). In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis, there were no adverse developmental outcomes; however, ototoxicity was not evaluated in the offspring from these studies (see Data). Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations are 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/or Embryo/Fetal Risk

Cystic fibrosis may increase the risk for preterm delivery.

Data

Animal Data

No reproductive toxicity studies have been conducted with tobramycin inhalation solution (tobramycin administered by inhalation). However, subcutaneous administration of tobramycin at doses of up to 100 (rat) or 20 (rabbit) mg/kg/day during organogenesis was not associated with adverse developmental outcomes. Doses of tobramycin ≥40 mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during non-clinical reproductive toxicity studies with tobramycin.

Risk Summary

There are no data on the presence of tobramycin in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Limited published data on other formulations of tobramycin in lactating women indicate that tobramycin is present in human milk. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. Tobramycin may cause alteration in the intestinal flora of the breastfeeding infant (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tobramycin and any potential adverse effects on the breastfed infant from tobramycin or from the underlying maternal condition.

Clinical Considerations

Tobramycin may cause intestinal flora alteration. Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).

The safety and efficacy of tobramycin inhalation solution in pediatric patients under 6 years of age has not been established. The use of tobramycin inhalation solution is not indicated in children <6 years of age [see Indications and Usage (1) and Dosage and Administration (2)].

Clinical studies of tobramycin inhalation solution did not include patients aged 65 years and over. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function [see Warnings and Precautions (5.3)].

Signs and symptoms of acute toxicity from overdosage of intravenous (IV) tobramycin might include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment.

{ "type": "p", "children": [], "text": "\nSigns and symptoms of acute toxicity from overdosage of intravenous (IV) tobramycin might include dizziness, tinnitus, vertigo, loss of high-tone hearing acuity, respiratory failure, neuromuscular blockade, and renal impairment." }

Administration by inhalation results in low systemic bioavailability of tobramycin. Tobramycin is not significantly absorbed following oral administration. Tobramycin serum concentrations may be helpful in monitoring overdosage.

{ "type": "p", "children": [], "text": "Administration by inhalation results in low systemic bioavailability of tobramycin. Tobramycin is not significantly absorbed following oral administration. Tobramycin serum concentrations may be helpful in monitoring overdosage." }

Acute toxicity should be treated with immediate withdrawal of tobramycin inhalation solution, and baseline tests of renal function should be undertaken.

{ "type": "p", "children": [], "text": "Acute toxicity should be treated with immediate withdrawal of tobramycin inhalation solution, and baseline tests of renal function should be undertaken." }

In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered.

{ "type": "p", "children": [], "text": "In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered." }

Hemodialysis may be helpful in removing tobramycin from the body.

{ "type": "p", "children": [], "text": "Hemodialysis may be helpful in removing tobramycin from the body." }

Tobramycin inhalation solution, USP is a tobramycin solution for inhalation. It is a sterile, clear, slightly yellow, non-pyrogenic, aqueous solution with the pH and salinity adjusted specifically for administration by a compressed air driven reusable nebulizer. The chemical formula for tobramycin is C18H37N5O9 and the molecular weight is 467.51 g/mol. Tobramycin is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine. The structural formula for tobramycin is:

{ "type": "p", "children": [], "text": "\nTobramycin inhalation solution, USP is a tobramycin solution for inhalation. It is a sterile, clear, slightly yellow, non-pyrogenic, aqueous solution with the pH and salinity adjusted specifically for administration by a compressed air driven reusable nebulizer. The chemical formula for tobramycin is C18H37N5O9 and the molecular weight is 467.51 g/mol. Tobramycin is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine. The structural formula for tobramycin is:" }

Each single-dose 5 mL ampule contains 300 mg tobramycin and 11.25 mg sodium chloride in sterile water for injection. Sulfuric acid and sodium hydroxide are added to adjust the pH to 6.0. Nitrogen is used for sparging. All ingredients meet USP requirements. The formulation contains no preservatives.

{ "type": "p", "children": [], "text": "\nEach single-dose 5 mL ampule contains 300 mg tobramycin and 11.25 mg sodium chloride in sterile water for injection. Sulfuric acid and sodium hydroxide are added to adjust the pH to 6.0. Nitrogen is used for sparging. All ingredients meet USP requirements. The formulation contains no preservatives." }

Tobramycin is an aminoglycoside antibacterial [see Microbiology (12.4)].

Absorption

Tobramycin inhalation solution contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes. (1)The bioavailability of tobramycin inhalation solution may vary because of individual differences in nebulizer performance and airway pathology. (2)Following administration of tobramycin inhalation solution, tobramycin remains concentrated primarily in the airways.

Serum Concentrations

The average serum concentration of tobramycin one hour after inhalation of a single 300-mg dose of tobramycin inhalation solution by cystic fibrosis patients was 0.95 mcg/mL. After 20 weeks of therapy on the tobramycin inhalation solution regimen, the average serum tobramycin concentration one hour after dosing was 1.05 mcg/mL.

Sputum Concentrations

Ten minutes after inhalation of the first 300-mg dose of tobramycin inhalation solution by cystic fibrosis patients, the average concentration of tobramycin was 1237 mcg/g (range 35 to 7417 mcg/g) in sputum. Tobramycin does not accumulate in sputum; after 20 weeks of therapy with the tobramycin inhalation solution regimen, the average concentration of tobramycin at ten minutes after inhalation was 1154 mcg/g (range 39 to 8085 mcg/g) in sputum. Two hours after inhalation, sputum concentrations declined to approximately 14% of tobramycin levels at ten minutes after inhalation.

Distribution

Following administration of tobramycin inhalation solution, tobramycin remains concentrated primarily in the airways. Binding of tobramycin to serum proteins is negligible.

Elimination

Metabolism

Tobramycin is not metabolized.

Excretion

The elimination half-life of tobramycin from serum is approximately 2 and 3 hours after intravenous (IV) administration and inhalation, respectively. Systemically absorbed tobramycin is primarily excreted unchanged in the urine principally by glomerular filtration. Unabsorbed tobramycin, following tobramycin inhalation solution administration, is probably eliminated primarily in expectorated sputum.

Mechanism of Action

Tobramycin is an aminoglycoside antibacterial produced by Streptomyces tenebrarius.(1) It acts primarily by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death.(3)

Tobramycin has in vitro activity against gram-negative bacteria including Pseudomonas aeruginosa. It is bactericidal in vitro at concentrations equal to or slightly greater than the minimum inhibitory concentration (MIC).

Resistance

Treatment for 6 months with tobramycin inhalation solution in two clinical studies did not affect the susceptibility of the majority of P. aeruginosa isolates tested; however, increased minimum inhibitory concentrations (MICs) were noted in some patients. The clinical significance of this information has not been clearly established in the treatment of P. aeruginosa in cystic fibrosis patients [see Clinical Studies (14)].

Susceptibility Test Methods

Interpretive criteria for inhaled antibacterial products are not defined. The in vitro antimicrobial susceptibility test methods used for parenteral tobramycin therapy can be used to monitor the susceptibility of P. aeruginosa isolated from cystic fibrosis patients. If decreased susceptibility is noted, the results should be reported to the clinician.

Susceptibility breakpoints established for parenteral administration of tobramycin do not apply to aerosolized administration of tobramycin inhalation solution. The relationship between in vitro susceptibility test results and clinical outcome with tobramycin inhalation solution therapy is not clear.

A single sputum sample from a cystic fibrosis patient may contain multiple morphotypes of Pseudomonas aeruginosa and each morphotype may have a different level of in vitro susceptibility to tobramycin.

A two-year rat inhalation toxicology study to assess carcinogenic potential of tobramycin inhalation solution has been completed. Rats were exposed to tobramycin inhalation solution for up to 1.5 hours per day for 95 weeks. The clinical formulation of the drug was used for this carcinogenicity study. Serum levels of tobramycin of up to 35 mcg/mL were measured in rats, in contrast to the average 1 mcg/mL levels observed in cystic fibrosis patients in clinical trials. There was no drug-related increase in the incidence of any variety of tumor.

Additionally, tobramycin has been evaluated for genotoxicity in a battery of in vitro and in vivo tests. The Ames bacterial reversion test, conducted with 5 tester strains, failed to show a significant increase in revertants with or without metabolic activation in all strains. Tobramycin was negative in the mouse lymphoma forward mutation assay, did not induce chromosomal aberrations in Chinese hamster ovary cells, and was negative in the mouse micronucleus test.

Subcutaneous administration of up to 100 mg/kg of tobramycin did not affect mating behavior or cause impairment of fertility in male or female rats.

Two identically designed, double-blind, randomized, placebo-controlled, parallel group, 24-week clinical studies (Study 1 and Study 2) at a total of 69 cystic fibrosis centers in the United States were conducted in cystic fibrosis patients with P. aeruginosa. Subjects who were less than 6 years of age, had a baseline creatinine of >2 mg/dL, or had Burkholderia cepacia isolated from sputum were excluded.

{ "type": "p", "children": [], "text": "\nTwo identically designed, double-blind, randomized, placebo-controlled, parallel group, 24-week clinical studies (Study 1 and Study 2) at a total of 69 cystic fibrosis centers in the United States were conducted in cystic fibrosis patients with P. aeruginosa. Subjects who were less than 6 years of age, had a baseline creatinine of >2 mg/dL, or had Burkholderia cepacia isolated from sputum were excluded." }

All subjects had baseline FEV1 % predicted between 25% and 75%. In these clinical studies, 258 patients received tobramycin inhalation solution therapy on an outpatient basis (see Table 2) using a hand-held PARI LC PLUS™  Reusable Nebulizer with a DeVilbiss® Pulmo-Aide® compressor.

{ "type": "p", "children": [], "text": "All subjects had baseline FEV1 % predicted between 25% and 75%. In these clinical studies, 258 patients received tobramycin inhalation solution therapy on an outpatient basis (see Table 2) using a hand-held PARI LC PLUS™  Reusable Nebulizer with a DeVilbiss® Pulmo-Aide® compressor." }

<div class="scrollingtable"><table class="Noautorules" width="99%"> <caption> <span> Table 2: Dosing Regimens in Clinical Studies </span> </caption> <col width="141"/> <col width="93"/> <col width="94"/> <col width="93"/> <col width="93"/> <col width="93"/> <col width="93"/> <tbody class="Headless"> <tr> <td class="Lrule Rrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"><span class="Bold"> Cycle 1</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"><span class="Bold"> Cycle 2</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" colspan="2" valign="top"><span class="Bold"> Cycle 3</span> <br/> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"></td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> 28 days</span> <br/> </td><td align="center" class="Botrule Rrule Toprule" valign="top"><span class="Bold"> 28 days</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> 28 days</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> 28 days</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> 28 days</span> <br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> 28 days</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> Tobramycin Inhalation Solution </span> <br/> regimen<br/> n = 258<br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Tobramycin Inhalation Solution</span> <br/> 300 mg<br/> twice daily<br/> </td><td align="center" class="Botrule Rrule" valign="top"> No drug<br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Tobramycin Inhalation Solution</span> <br/> 300 mg<br/> twice daily<br/> </td><td align="center" class="Botrule Rrule" valign="top"> No drug<br/> </td><td align="center" class="Botrule Rrule" valign="top"><span class="Bold"> Tobramycin Inhalation Solution</span> <br/> 300 mg<br/> twice daily<br/> </td><td align="center" class="Botrule Rrule" valign="top"> No drug<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"> Placebo regimen<br/>  n = 262<br/> </td><td align="center" class="Botrule Rrule" valign="top"> placebo<br/> twice daily<br/> </td><td align="center" class="Botrule Rrule" valign="top"> No drug<br/> </td><td align="center" class="Botrule Rrule" valign="top"> placebo<br/> twice daily<br/> </td><td align="center" class="Botrule Rrule" valign="top"> No drug<br/> </td><td align="center" class="Botrule Rrule" valign="top"> placebo<br/> twice daily<br/> </td><td align="center" class="Botrule Rrule" valign="top"> No drug<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"99%\">\n<caption>\n<span> Table 2: Dosing Regimens in Clinical Studies </span>\n</caption>\n<col width=\"141\"/>\n<col width=\"93\"/>\n<col width=\"94\"/>\n<col width=\"93\"/>\n<col width=\"93\"/>\n<col width=\"93\"/>\n<col width=\"93\"/>\n<tbody class=\"Headless\">\n<tr>\n<td class=\"Lrule Rrule Toprule\" valign=\"top\"></td><td align=\"center\" class=\"Botrule Rrule Toprule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\"> Cycle 1</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\"> Cycle 2</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" colspan=\"2\" valign=\"top\"><span class=\"Bold\"> Cycle 3</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" valign=\"top\"></td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> 28 days</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule Toprule\" valign=\"top\"><span class=\"Bold\"> 28 days</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> 28 days</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> 28 days</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> 28 days</span>\n<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> 28 days</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> Tobramycin Inhalation Solution </span>\n<br/> regimen<br/> n = 258<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> Tobramycin Inhalation Solution</span>\n<br/> 300 mg<br/> twice daily<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> No drug<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> Tobramycin Inhalation Solution</span>\n<br/> 300 mg<br/> twice daily<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> No drug<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"><span class=\"Bold\"> Tobramycin Inhalation Solution</span>\n<br/> 300 mg<br/> twice daily<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> No drug<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"> Placebo regimen<br/>  n = 262<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> placebo<br/> twice daily<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> No drug<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> placebo<br/> twice daily<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> No drug<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> placebo<br/> twice daily<br/>\n</td><td align=\"center\" class=\"Botrule Rrule\" valign=\"top\"> No drug<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

All patients received either tobramycin inhalation solution or placebo (saline with 1.25 mg quinine for flavoring) in addition to standard treatment recommended for cystic fibrosis patients, which included oral and parenteral antipseudomonal therapy, β2-agonists, cromolyn, inhaled steroids, and airway clearance techniques. In addition, approximately 77% of patients were concurrently treated with dornase alfa (PULMOZYME, Genentech).

{ "type": "p", "children": [], "text": "\nAll patients received either tobramycin inhalation solution or placebo (saline with 1.25 mg quinine for flavoring) in addition to standard treatment recommended for cystic fibrosis patients, which included oral and parenteral antipseudomonal therapy, β2-agonists, cromolyn, inhaled steroids, and airway clearance techniques. In addition, approximately 77% of patients were concurrently treated with dornase alfa (PULMOZYME, Genentech)." }

In each study, tobramycin inhalation solution-treated patients experienced significant improvement in pulmonary function. Improvement was demonstrated in the tobramycin inhalation solution group in Study 1 by an average increase in FEV1 % predicted of about 11% relative to baseline (Week 0) during 24 weeks compared to no average change in placebo patients. In Study 2, tobramycin inhalation solution-treated patients had an average increase of about 7% compared to an average decrease of about 1% in placebo patients. Figure 1 shows the average relative change in FEV1% predicted over 24 weeks for both studies.

{ "type": "p", "children": [], "text": "In each study, tobramycin inhalation solution-treated patients experienced significant improvement in pulmonary function. Improvement was demonstrated in the tobramycin inhalation solution group in Study 1 by an average increase in FEV1 % predicted of about 11% relative to baseline (Week 0) during 24 weeks compared to no average change in placebo patients. In Study 2, tobramycin inhalation solution-treated patients had an average increase of about 7% compared to an average decrease of about 1% in placebo patients. Figure 1 shows the average relative change in FEV1% predicted over 24 weeks for both studies." }

In each study, tobramycin inhalation solution therapy resulted in a significant reduction in the number of P. aeruginosa colony forming units (CFUs) in sputum during the on-drug periods. Sputum bacterial density returned to baseline during the off-drug periods. Reductions in sputum bacterial density were smaller in each successive cycle (see Figure 2).

{ "type": "p", "children": [], "text": "\nIn each study, tobramycin inhalation solution therapy resulted in a significant reduction in the number of P. aeruginosa colony forming units (CFUs) in sputum during the on-drug periods. Sputum bacterial density returned to baseline during the off-drug periods. Reductions in sputum bacterial density were smaller in each successive cycle (see Figure 2)." }

Patients treated with tobramycin inhalation solution were hospitalized for an average of 5.1 days compared to 8.1 days for placebo patients. Patients treated with tobramycin inhalation solution required an average of 9.6 days of parenteral antipseudomonal, antibacterial treatment compared to 14.1 days for placebo patients. During the 6 months of treatment, 40% of tobramycin inhalation solution patients and 53% of placebo patients were treated with parenteral antipseudomonal antibacterials.

{ "type": "p", "children": [], "text": "\nPatients treated with tobramycin inhalation solution were hospitalized for an average of 5.1 days compared to 8.1 days for placebo patients. Patients treated with tobramycin inhalation solution required an average of 9.6 days of parenteral antipseudomonal, antibacterial treatment compared to 14.1 days for placebo patients. During the 6 months of treatment, 40% of tobramycin inhalation solution patients and 53% of placebo patients were treated with parenteral antipseudomonal antibacterials." }

The relationship between in vitro susceptibility test results and clinical outcome with tobramycin inhalation solution therapy is not clear. However, four tobramycin inhalation solution patients who began the clinical trial with P. aeruginosa isolates having MIC values ≥128 mcg/mL did not experience an improvement in FEV1 or a decrease in sputum bacterial density.

{ "type": "p", "children": [], "text": "The relationship between in vitro susceptibility test results and clinical outcome with tobramycin inhalation solution therapy is not clear. However, four tobramycin inhalation solution patients who began the clinical trial with P. aeruginosa isolates having MIC values ≥128 mcg/mL did not experience an improvement in FEV1 or a decrease in sputum bacterial density." }

Treatment with tobramycin inhalation solution did not affect the susceptibility of the majority of P. aeruginosa isolates during the 6-month studies. However, some P. aeruginosa isolates did exhibit increased tobramycin MICs. The percentage of patients with P. aeruginosa isolates with tobramycin MICs ≥16 mcg/mL was 13% at the beginning, and 23% at the end of 6 months of the tobramycin inhalation solution regimen.

{ "type": "p", "children": [], "text": "Treatment with tobramycin inhalation solution did not affect the susceptibility of the majority of P. aeruginosa isolates during the 6-month studies. However, some P. aeruginosa isolates did exhibit increased tobramycin MICs. The percentage of patients with P. aeruginosa isolates with tobramycin MICs ≥16 mcg/mL was 13% at the beginning, and 23% at the end of 6 months of the tobramycin inhalation solution regimen." }

1.      Neu HC. Tobramycin: an overview. [Review]. J Infect Dis 1976; Suppl 134:S3-19.

{ "type": "p", "children": [], "text": "\n1.      Neu HC. Tobramycin: an overview. [Review]. J Infect Dis 1976; Suppl 134:S3-19. " }

2.      Weber A, Smith A, Williams-Warren J et al. Nebulizer delivery of tobramycin to the lower respiratory tract. Pediatr Pulmonol 1994; 17 (5):331-9.

{ "type": "p", "children": [], "text": "2.      Weber A, Smith A, Williams-Warren J et al. Nebulizer delivery of tobramycin to the lower respiratory tract. Pediatr Pulmonol 1994; 17 (5):331-9." }

3.      Bryan LE. Aminoglycoside resistance. Bryan LE, Ed. Antimicrobial drug resistance. Orlando, FL: Academic Press, 1984: 241-77.

{ "type": "p", "children": [], "text": "3.      Bryan LE. Aminoglycoside resistance. Bryan LE, Ed. Antimicrobial drug resistance. Orlando, FL: Academic Press, 1984: 241-77." }

Tobramycin inhalation solution, USP, 300 mg is supplied as a sterile, clear, slightly yellow, non-pyrogenic, aqueous solution packaged in a 5 mL single-dose ampule (300 mg tobramycin) for nebulization.

Tobramycin inhalation solution, USP 300 mg is available as follows:

NDC 68180-962-56

5 mL single-dose ampule packed in carton of 56 ampules (14 pouches, each containing 4 ampules).

Tobramycin inhalation solution, USP should be stored under refrigeration at 2 to 8ºC/36 to 46ºF. Upon removal from the refrigerator, or if refrigeration is unavailable, tobramycin inhalation solution, USP pouches (opened or unopened) may be stored at room temperature (up to 25ºC/77ºF) for up to 28 days. Tobramycin inhalation solution, USP should not be used beyond the expiration date stamped on the ampule when stored under refrigeration (2 to 8ºC/36 to 46ºF) or beyond 28 days when stored at room temperature (25ºC/77ºF).

Tobramycin inhalation solution, USP ampules should not be exposed to intense light. The solution in the ampule is slightly yellow, but may darken with age if not stored in the refrigerator; however, the color change does not indicate any change in the quality of the product as long as it is stored within the recommended storage conditions.

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

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

Difficulty Breathing:

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

Advise patients to inform their physicians if they experience shortness of breath or wheezing after administration of tobramycin inhalation solution. Tobramycin inhalation solution can cause a narrowing of the airway [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients to inform their physicians if they experience shortness of breath or wheezing after administration of tobramycin inhalation solution. Tobramycin inhalation solution can cause a narrowing of the airway [see Warnings and Precautions (5.1)].\n" }

Hearing Loss:

{ "type": "p", "children": [], "text": "\nHearing Loss:" }

Advise patients to inform their physician if they experience ringing in the ears, dizziness, or any changes in hearing because tobramycin inhalation solution has been associated with hearing loss [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to inform their physician if they experience ringing in the ears, dizziness, or any changes in hearing because tobramycin inhalation solution has been associated with hearing loss [see Warnings and Precautions (5.2)].\n" }

Kidney Damage:

{ "type": "p", "children": [], "text": "\nKidney Damage:" }

Advise patients to inform their physician if they have any history of kidney problems because tobramycin inhalation solution is in a class of drugs that have caused kidney damage [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients to inform their physician if they have any history of kidney problems because tobramycin inhalation solution is in a class of drugs that have caused kidney damage [see Warnings and Precautions (5.3)]." }

Embryo-fetal Toxicity:

{ "type": "p", "children": [], "text": "\nEmbryo-fetal Toxicity:\n" }

Advise pregnant women that aminoglycosides can cause irreversible congenital deafness when administered to a pregnant woman [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise pregnant women that aminoglycosides can cause irreversible congenital deafness when administered to a pregnant woman [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].\n" }

Lactation:

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

Advise a woman to monitor their breastfed infants for diarrhea and/or bloody stools [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise a woman to monitor their breastfed infants for diarrhea and/or bloody stools [see Use in Specific Populations (8.2)].\n" }

®The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

{ "type": "p", "children": [], "text": "\n®The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products." }

Manufactured for:

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

Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "\nLupin Pharmaceuticals, Inc." }

Naples, FL 34108

{ "type": "p", "children": [], "text": "Naples, FL 34108" }

United States

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

Revised: July 2025

{ "type": "p", "children": [], "text": "Revised: July 2025" }

<div class="scrollingtable"><table class="Noautorules" width="638"> <col width="638"/> <tbody class="Headless"> <tr> <td align="center" class="Botrule Lrule Rrule Toprule" valign="top"><span class="Bold"> PATIENT INFORMATION</span> <br/> <span class="Bold"> Tobramycin (Toe-Bra-MYE-Sin)</span> <br/> <span class="Bold"> Inhalation Solution, USP</span> <br/> <span class="Bold"> for oral inhalation use</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> What is </span><span class="Bold"> Tobramycin Inhalation Solution?</span> <br/> Tobramycin inhalation solution is a prescription medicine that is used to treat people with cystic fibrosis who have a bacterial infection called <span class="Italics">Pseudomonas aeruginosa</span> . Tobramycin inhalation solution contains an antibacterial medicine called tobramycin (an aminoglycoside).<br/> It is not known if tobramycin inhalation solution is safe and effective:<br/>         •    in children under 6 years of age<br/>         •    in people who have an FEV<span class="Sub">1</span> less than 25% or greater than 75% predicted<br/>         •    in people who are colonized with a bacterium called <span class="Italics">Burkholderia cepacia</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> Do not take </span><span class="Bold"> tobramycin inhalation solution</span> if you are allergic to tobramycin, any of the ingredients in tobramycin inhalation solution, or to any other aminoglycoside antibacterial.<br/> <span class="Bold"> See the end of this Patient Information for a complete list of ingredients in </span><span class="Bold"> tobramycin inhalation solution.</span> <br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> Before you take </span><span class="Bold"> tobramycin inhalation solution, tell your healthcare provider about all of your medical conditions, including if you:</span> <br/>         •    have or have had hearing problems (including noises in your ears such as ringing or hissing), hearing loss, or your mother has had hearing problems after taking an aminoglycoside.<br/>         •    have been told you have certain gene variants (a change in the gene) related to hearing abnormalities inherited from your mother.<br/>         •    have dizziness<br/>         •    have or have had kidney problems<br/>         •  have or have had problems with muscle weakness such as myasthenia gravis or Parkinson's disease<br/>         •    have or have had breathing problems such as wheezing, coughing, or chest tightness<br/>         •   are pregnant or plan to become pregnant. Tobramycin inhalation solution is in a class of drugs that can harm your unborn baby.<br/>         •   are breastfeeding or plan to breastfeed. It is not known if tobramycin passes into your breast milk.<br/>         •   are receiving aminoglycoside therapy by injection or through a vein (intravenous) while taking tobramycin inhalation solution. Your blood levels of tobramycin will be checked.<br/> <span class="Bold"> Tell your healthcare provider about all the medicines you take, </span> including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> How should I take </span><span class="Bold"> tobramycin inhalation solution?</span> <br/>         •    <span class="Bold"> See the step-by-step Instructions for Use </span> about the right way to take your tobramycin inhalation solution.<br/>         •    Take tobramycin inhalation solution exactly as your healthcare provider tells you. <span class="Bold"> Do not </span> change your dose or stop taking tobramycin inhalation solution unless your healthcare provider tells you to.<br/>         •    The usual dose for adults and children over 6 years of age is:<br/>                 ο     1 single-use ampule of tobramycin inhalation solution inhaled 2 times each day using a hand-held PARI LC PLUS™ Reusable Nebulizer and a DeVilbiss® Pulmo-Aide® air compressor.<br/>         •    Each dose of tobramycin inhalation solution should be taken as close to 12 hours apart as possible.<br/>         •    You should not take your dose less than 6 hours apart.<br/>         •    Tobramycin inhalation solution is taken as a breathing treatment (inhalation) with a hand-held PARI LC PLUS<span class="Sup">™</span> Reusable Nebulizer with a DeVilbiss<span class="Sup">®</span> Pulmo-Aide<span class="Sup">®</span> compressor. <span class="Bold"> Do not </span> use any other nebulizer for your tobramycin inhalation solution treatment.<br/>         •    Do not mix or dilute tobramycin inhalation solution with dornase alfa or other medicines in your nebulizer system.<br/>         •    Each treatment should take about 15 minutes.<br/>         •    Tobramycin inhalation solution should be inhaled while you are sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help you to breathe through your mouth.<br/>         •    If you forget to take tobramycin inhalation solution and there are at least 6 hours to your next dose, take your dose as soon as you can. Otherwise, wait for your next dose. Do not double the dose to make up for the missed dose.<br/>         •    After using tobramycin inhalation solution for 28 days, you should stop using it and wait 28 days. After you have stopped using tobramycin inhalation solution for 28 days, you should start using tobramycin inhalation solution again for 28 days. Complete the full 28-day course even if you are feeling better. It is important that you keep to the 28-day on, 28-day off cycle.<br/> If you are taking several medicines or treatments to treat your cystic fibrosis, you should take your medicines or other treatments before inhaling tobramycin inhalation solution or as directed by your healthcare provider. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter prescription medicines, vitamins, and herbal supplements.<br/> Using tobramycin inhalation solution with certain other medicines can cause serious side effects.<br/> If you are using tobramycin inhalation solution, you should discuss with your healthcare provider if you should take:<br/>         •    other medicines that may harm your nervous system, kidneys, or hearing<br/>         •     "water pills" (diuretics) such as ethacrynic acid, furosemide, or intravenous mannitol<br/>         •    urea<br/> Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.<br/> Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> What are the possible side effects of </span><span class="Bold"> tobramycin inhalation solution?</span> <br/> <span class="Bold"> Tobramycin inhalation solution may cause serious side effects, including:</span> <br/>         •    severe breathing problems (bronchospasm). Tell your healthcare provider right away if you get any of these symptoms of bronchospasm with using tobramycin inhalation solution:<br/>                 ο     shortness of breath with wheezing<br/>                 ο     coughing and chest tightness<br/>         •    hearing loss or ringing in the ears (ototoxicity). Tell your healthcare provider right away if you have hearing loss or you hear noises in your ears such as ringing or hissing. Tell your healthcare provider if you develop vertigo, difficulty with balance or dizziness.<br/>         •    worsening kidney problems (nephrotoxicity). Tobramycin inhalation solution is in a class of drugs which may cause worsening kidney problems, especially in people with known or suspected kidney problems. Your healthcare provider may do a blood test to check how your kidneys are working while you are using tobramycin inhalation solution.<br/>         •    worsening muscle weakness (neuromuscular disorder). Tobramycin inhalation solution is in a class of drugs which can cause muscle weakness to get worse in people who already have problems with muscle weakness (myasthenia gravis or Parkinson's disease).<br/> The most common side effects of tobramycin inhalation solution include:<br/>                 ο     increased cough <br/>                 ο     sore throat <br/>                 ο     increased sputum<br/>                 ο     coughing up blood o decreased lung function <br/>                 ο     trouble breathing<br/>                 ο     voice changes o loss or change in taste <br/>                 ο     rash<br/> These are not all of the possible side effects of tobramycin inhalation solution.<br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> General information about the safe and effective use of </span><span class="Bold"> tobramycin inhalation solution</span> <br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use tobramycin inhalation solution for a condition for which it was not prescribed. Do not give it to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about tobramycin inhalation solution that is written for health professionals.<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> What are the ingredients in </span><span class="Bold"> tobramycin inhalation solution?</span> <br/> <span class="Bold"> Active ingredient: </span> tobramycin<br/> <span class="Bold"> Inactive ingredients: </span> sodium chloride in sterile water for injection, sulfuric acid, sodium hydroxide, and nitrogen<br/> </td> </tr> <tr> <td align="left" class="Botrule Lrule Rrule" valign="top"><span class="Bold"> What is Pseudomonas aeruginosa?</span> <br/> It is a very common bacterium that infects the lungs of nearly everyone with cystic fibrosis at some time during their lives.<br/> Some people do not get this infection until later in their lives, while others get it very young. It is one of the most damaging bacteria for people with cystic fibrosis. If the infection is not properly managed, it will continue to damage your lungs causing further problems to your breathing.<br/> For more information, go to www.lupinpharmaceuticals.com or call 1-800-399-2561.<br/> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"638\">\n<col width=\"638\"/>\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" valign=\"top\"><span class=\"Bold\"> PATIENT INFORMATION</span>\n<br/>\n<span class=\"Bold\"> Tobramycin (Toe-Bra-MYE-Sin)</span>\n<br/>\n<span class=\"Bold\"> Inhalation Solution, USP</span>\n<br/>\n<span class=\"Bold\"> for oral inhalation use</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> What is </span><span class=\"Bold\"> Tobramycin Inhalation Solution?</span>\n<br/> Tobramycin inhalation solution is a prescription medicine that is used to treat people with cystic fibrosis who have a bacterial infection called <span class=\"Italics\">Pseudomonas aeruginosa</span> . Tobramycin inhalation solution contains an antibacterial medicine called tobramycin (an aminoglycoside).<br/> It is not known if tobramycin inhalation solution is safe and effective:<br/>         •    in children under 6 years of age<br/>         •    in people who have an FEV<span class=\"Sub\">1</span> less than 25% or greater than 75% predicted<br/>         •    in people who are colonized with a bacterium called <span class=\"Italics\">Burkholderia cepacia</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> Do not take </span><span class=\"Bold\"> tobramycin inhalation solution</span> if you are allergic to tobramycin, any of the ingredients in tobramycin inhalation solution, or to any other aminoglycoside antibacterial.<br/>\n<span class=\"Bold\"> See the end of this Patient Information for a complete list of ingredients in </span><span class=\"Bold\"> tobramycin inhalation solution.</span>\n<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> Before you take </span><span class=\"Bold\"> tobramycin inhalation solution, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<br/>         •    have or have had hearing problems (including noises in your ears such as ringing or hissing), hearing loss, or your mother has had hearing problems after taking an aminoglycoside.<br/>         •    have been told you have certain gene variants (a change in the gene) related to hearing abnormalities inherited from your mother.<br/>         •    have dizziness<br/>         •    have or have had kidney problems<br/>         •  have or have had problems with muscle weakness such as myasthenia gravis or Parkinson's disease<br/>         •    have or have had breathing problems such as wheezing, coughing, or chest tightness<br/>         •   are pregnant or plan to become pregnant. Tobramycin inhalation solution is in a class of drugs that can harm your unborn baby.<br/>         •   are breastfeeding or plan to breastfeed. It is not known if tobramycin passes into your breast milk.<br/>         •   are receiving aminoglycoside therapy by injection or through a vein (intravenous) while taking tobramycin inhalation solution. Your blood levels of tobramycin will be checked.<br/>\n<span class=\"Bold\"> Tell your healthcare provider about all the medicines you take, </span> including prescription medicines, over-the-counter medicines, vitamins, and herbal supplements.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> How should I take </span><span class=\"Bold\"> tobramycin inhalation solution?</span>\n<br/>         •    <span class=\"Bold\"> See the step-by-step Instructions for Use </span> about the right way to take your tobramycin inhalation solution.<br/>         •    Take tobramycin inhalation solution exactly as your healthcare provider tells you. <span class=\"Bold\"> Do not </span> change your dose or stop taking tobramycin inhalation solution unless your healthcare provider tells you to.<br/>         •    The usual dose for adults and children over 6 years of age is:<br/>                 ο     1 single-use ampule of tobramycin inhalation solution inhaled 2 times each day using a hand-held PARI LC PLUS™ Reusable Nebulizer and a DeVilbiss® Pulmo-Aide® air compressor.<br/>         •    Each dose of tobramycin inhalation solution should be taken as close to 12 hours apart as possible.<br/>         •    You should not take your dose less than 6 hours apart.<br/>         •    Tobramycin inhalation solution is taken as a breathing treatment (inhalation) with a hand-held PARI LC PLUS<span class=\"Sup\">™</span> Reusable Nebulizer with a DeVilbiss<span class=\"Sup\">®</span> Pulmo-Aide<span class=\"Sup\">®</span> compressor. <span class=\"Bold\"> Do not </span> use any other nebulizer for your tobramycin inhalation solution treatment.<br/>         •    Do not mix or dilute tobramycin inhalation solution with dornase alfa or other medicines in your nebulizer system.<br/>         •    Each treatment should take about 15 minutes.<br/>         •    Tobramycin inhalation solution should be inhaled while you are sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help you to breathe through your mouth.<br/>         •    If you forget to take tobramycin inhalation solution and there are at least 6 hours to your next dose, take your dose as soon as you can. Otherwise, wait for your next dose. Do not double the dose to make up for the missed dose.<br/>         •    After using tobramycin inhalation solution for 28 days, you should stop using it and wait 28 days. After you have stopped using tobramycin inhalation solution for 28 days, you should start using tobramycin inhalation solution again for 28 days. Complete the full 28-day course even if you are feeling better. It is important that you keep to the 28-day on, 28-day off cycle.<br/> If you are taking several medicines or treatments to treat your cystic fibrosis, you should take your medicines or other treatments before inhaling tobramycin inhalation solution or as directed by your healthcare provider. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter prescription medicines, vitamins, and herbal supplements.<br/> Using tobramycin inhalation solution with certain other medicines can cause serious side effects.<br/> If you are using tobramycin inhalation solution, you should discuss with your healthcare provider if you should take:<br/>         •    other medicines that may harm your nervous system, kidneys, or hearing<br/>         •     \"water pills\" (diuretics) such as ethacrynic acid, furosemide, or intravenous mannitol<br/>         •    urea<br/> Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure.<br/> Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> What are the possible side effects of </span><span class=\"Bold\"> tobramycin inhalation solution?</span>\n<br/>\n<span class=\"Bold\"> Tobramycin inhalation solution may cause serious side effects, including:</span>\n<br/>         •    severe breathing problems (bronchospasm). Tell your healthcare provider right away if you get any of these symptoms of bronchospasm with using tobramycin inhalation solution:<br/>                 ο     shortness of breath with wheezing<br/>                 ο     coughing and chest tightness<br/>         •    hearing loss or ringing in the ears (ototoxicity). Tell your healthcare provider right away if you have hearing loss or you hear noises in your ears such as ringing or hissing. Tell your healthcare provider if you develop vertigo, difficulty with balance or dizziness.<br/>         •    worsening kidney problems (nephrotoxicity). Tobramycin inhalation solution is in a class of drugs which may cause worsening kidney problems, especially in people with known or suspected kidney problems. Your healthcare provider may do a blood test to check how your kidneys are working while you are using tobramycin inhalation solution.<br/>         •    worsening muscle weakness (neuromuscular disorder). Tobramycin inhalation solution is in a class of drugs which can cause muscle weakness to get worse in people who already have problems with muscle weakness (myasthenia gravis or Parkinson's disease).<br/> The most common side effects of tobramycin inhalation solution include:<br/>                 ο     increased cough <br/>                 ο     sore throat <br/>                 ο     increased sputum<br/>                 ο     coughing up blood o decreased lung function <br/>                 ο     trouble breathing<br/>                 ο     voice changes o loss or change in taste <br/>                 ο     rash<br/> These are not all of the possible side effects of tobramycin inhalation solution.<br/> Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> General information about the safe and effective use of </span><span class=\"Bold\"> tobramycin inhalation solution</span>\n<br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use tobramycin inhalation solution for a condition for which it was not prescribed. Do not give it to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for more information about tobramycin inhalation solution that is written for health professionals.<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> What are the ingredients in </span><span class=\"Bold\"> tobramycin inhalation solution?</span>\n<br/>\n<span class=\"Bold\"> Active ingredient: </span> tobramycin<br/>\n<span class=\"Bold\"> Inactive ingredients: </span> sodium chloride in sterile water for injection, sulfuric acid, sodium hydroxide, and nitrogen<br/>\n</td>\n</tr>\n<tr>\n<td align=\"left\" class=\"Botrule Lrule Rrule\" valign=\"top\"><span class=\"Bold\"> What is Pseudomonas aeruginosa?</span>\n<br/> It is a very common bacterium that infects the lungs of nearly everyone with cystic fibrosis at some time during their lives.<br/> Some people do not get this infection until later in their lives, while others get it very young. It is one of the most damaging bacteria for people with cystic fibrosis. If the infection is not properly managed, it will continue to damage your lungs causing further problems to your breathing.<br/> For more information, go to www.lupinpharmaceuticals.com or call 1-800-399-2561.<br/>\n</td>\n</tr>\n</tbody>\n</table></div>" }

This Patient Information has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "\nThis Patient Information has been approved by the U.S. Food and Drug Administration." }

®The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

{ "type": "p", "children": [], "text": "\n®The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products." }

Instructions for Use

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

Tobramycin (Toe-Bra-MYE-Sin)

{ "type": "p", "children": [], "text": "\nTobramycin (Toe-Bra-MYE-Sin)\n" }

Inhalation Solution, USP

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

for oral inhalation use

{ "type": "p", "children": [], "text": "\nfor oral inhalation use \n" }

Read this Instructions for Use before you start using tobramycin inhalation solution and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment.

{ "type": "p", "children": [], "text": "Read this Instructions for Use before you start using tobramycin inhalation solution and each time you get a refill. There may be new information. This leaflet does not take the place of talking to your healthcare provider about your medical condition or treatment." }

Tobramycin inhalation solution is made for inhalation using a PARI LC PLUS™ Reusable Nebulizer and a DeVilbiss® Pulmo-Aide® air compressor. Tobramycin inhalation solution can be taken at home, school, or at work. The following instructions tell you how to use the DeVilbiss® Pulmo-Aide® air compressor and PARI LC PLUS™ Reusable Nebulizer to administer tobramycin inhalation solution.

{ "type": "p", "children": [], "text": "Tobramycin inhalation solution is made for inhalation using a PARI LC PLUS™ Reusable Nebulizer and a DeVilbiss® Pulmo-Aide® air compressor. Tobramycin inhalation solution can be taken at home, school, or at work. The following instructions tell you how to use the DeVilbiss® Pulmo-Aide® air compressor and PARI LC PLUS™ Reusable Nebulizer to administer tobramycin inhalation solution." }

You will need the following supplies (See Figure A):

{ "type": "p", "children": [], "text": "\nYou will need the following supplies (See Figure A):\n" }

{ "type": "ul", "children": [ "  One tobramycin inhalation solution plastic ampule (tobramycin inhalation solution is packaged with 4 ampules in each foil pouch)", "  DeVilbiss®Pulmo-Aide®air compressor", "  PARI LC PLUS™Reusable Nebulizer", "  Tubing to connect the nebulizer and compressor", "  Clean paper or cloth towels", "  Nose clips (optional)" ], "text": "" }

It is important that your nebulizer and compressor function properly before starting your tobramycin inhalation solution therapy.

{ "type": "p", "children": [], "text": "\nIt is important that your nebulizer and compressor function properly before starting your tobramycin inhalation solution therapy." }

Note: Read the manufacturer care and use instructions for important information.

{ "type": "p", "children": [], "text": "Note: Read the manufacturer care and use instructions for important information." }

Prepare Your Tobramycin Inhalation Solution for Inhalation Therapy

{ "type": "p", "children": [], "text": "\nPrepare Your Tobramycin Inhalation Solution for Inhalation Therapy\n" }

Step 1: Wash your hands thoroughly with soap and water.

{ "type": "p", "children": [], "text": "\nStep 1: Wash your hands thoroughly with soap and water." }

Step 2: Open the foil pouch.

{ "type": "p", "children": [], "text": "\nStep 2: Open the foil pouch." }

Step 3: Separate one tobramycin inhalation solution ampule by gently pulling apart at the bottom tabs (See Figure B). Place the remaining tobramycin inhalation solution ampules in the refrigerator.

{ "type": "p", "children": [], "text": "\nStep 3: Separate one tobramycin inhalation solution ampule by gently pulling apart at the bottom tabs (See Figure B). Place the remaining tobramycin inhalation solution ampules in the refrigerator." }

Step 4: Check the expiration date stamped on the tobramycin inhalation solution ampule (See Figure C). Do not use the tobramycin inhalation solution ampule if the expiration date has passed.

{ "type": "p", "children": [], "text": "\nStep 4: Check the expiration date stamped on the tobramycin inhalation solution ampule (See Figure C). Do not use the tobramycin inhalation solution ampule if the expiration date has passed." }

Step 5: Check that the tobramycin inhalation solution ampule medicine is clear and does not have particles.

{ "type": "p", "children": [], "text": "\nStep 5: Check that the tobramycin inhalation solution ampule medicine is clear and does not have particles." }

{ "type": "ul", "children": [ "Unrefrigerated tobramycin inhalation solution, which is normally slightly yellow, may darken with age. This color change does not mean there is any change in the quality of the medicine.", "\nDo not use the tobramycin inhalation solution ampule if the medicine is cloudy or has particles.", "Throw it away and get a new one." ], "text": "" }

Step 6: Lay out the parts of a PARI LC PLUSTM Reusable Nebulizer package on a clean, dry paper or cloth towel. You should have the following parts (See Figure D):

{ "type": "p", "children": [], "text": "\nStep 6: Lay out the parts of a PARI LC PLUSTM Reusable Nebulizer package on a clean, dry paper or cloth towel. You should have the following parts (See Figure D):\n" }

{ "type": "ul", "children": [ "Nebulizer Top and Bottom (Nebulizer Cup) Assembly", "Inspiratory Valve Cap", "Mouthpiece with Valve", "Tubing" ], "text": "" }

Step 7: Remove the Nebulizer Top from the Nebulizer Cup by twisting the Nebulizer Top counter-clockwise, and then lifting off (See Figure E).

{ "type": "p", "children": [], "text": "\nStep 7: Remove the Nebulizer Top from the Nebulizer Cup by twisting the Nebulizer Top counter-clockwise, and then lifting off (See Figure E)." }

Step 8: Place the Nebulizer Top on the clean paper or cloth towel by standing the Nebulizer Cup upright on the towel (See Figure F).

{ "type": "p", "children": [], "text": "\nStep 8: Place the Nebulizer Top on the clean paper or cloth towel by standing the Nebulizer Cup upright on the towel (See Figure F).\n" }

Step 9: Connect one end of the tubing to the compressor air outlet (See Figure G). The tubing should fit tightly.

{ "type": "p", "children": [], "text": "\nStep 9: Connect one end of the tubing to the compressor air outlet (See Figure G). The tubing should fit tightly." }

Step 10: Plug in your compressor to an electrical outlet (See Figure H).

{ "type": "p", "children": [], "text": "\nStep 10: Plug in your compressor to an electrical outlet (See Figure H)." }

Step 11: Open the tobramycin inhalation solution ampule by holding the bottom tab with one hand and twisting off the top of the tobramycin inhalation solution ampule with the other hand (See Figure I). Be careful not to squeeze the tobramycin inhalation solution ampule until you are ready to empty all the medicine into the Nebulizer Cup.

{ "type": "p", "children": [], "text": "\nStep 11: Open the tobramycin inhalation solution ampule by holding the bottom tab with one hand and twisting off the top of the tobramycin inhalation solution ampule with the other hand (See Figure I). Be careful not to squeeze the tobramycin inhalation solution ampule until you are ready to empty all the medicine into the Nebulizer Cup." }

Step 12: Squeeze all the medicine of the tobramycin inhalation solution ampule into the Nebulizer Cup (See Figure J).

{ "type": "p", "children": [], "text": "\nStep 12: Squeeze all the medicine of the tobramycin inhalation solution ampule into the Nebulizer Cup (See Figure J)." }

Step 13: Replace the Nebulizer Top. To replace the Nebulizer Top insert the Nebulizer Top into the Nebulizer Cup with the semi-circle halfway down the stem of the Nebulizer Top facing the Nebulizer Outlet. Turn the Nebulizer Top clockwise until securely fastened to the nebulizer Cup. (See Figure K).

{ "type": "p", "children": [], "text": "\nStep 13: Replace the Nebulizer Top. To replace the Nebulizer Top insert the Nebulizer Top into the Nebulizer Cup with the semi-circle halfway down the stem of the Nebulizer Top facing the Nebulizer Outlet. Turn the Nebulizer Top clockwise until securely fastened to the nebulizer Cup. (See Figure K).\n" }

Step 14: Push the Mouthpiece straight onto the Nebulizer Outlet (See Figure L).

{ "type": "p", "children": [], "text": "\nStep 14: Push the Mouthpiece straight onto the Nebulizer Outlet (See Figure L)." }

Step 15: Firmly push the Inspiratory Valve Cap straight down onto the Nebulizer Top (See Figure M). The Inspiratory Valve Cap will fit tightly.

{ "type": "p", "children": [], "text": "\nStep 15: Firmly push the Inspiratory Valve Cap straight down onto the Nebulizer Top (See Figure M). The Inspiratory Valve Cap will fit tightly." }

Step 16: Hold the Nebulizer Cup upright and firmly push the free end of the tubing from the compressor to the Air Intake on the bottom of the Nebulizer Cup (See Figure N). Make sure to keep the Nebulizer Cup upright.

{ "type": "p", "children": [], "text": "\nStep 16: Hold the Nebulizer Cup upright and firmly push the free end of the tubing from the compressor to the Air Intake on the bottom of the Nebulizer Cup (See Figure N). Make sure to keep the Nebulizer Cup upright.\n" }

Giving your Tobramycin Inhalation Solution Inhalation Therapy

{ "type": "p", "children": [], "text": "\nGiving your Tobramycin Inhalation Solution Inhalation Therapy\n" }

Step 17: Turn on the compressor (See Figure O).

{ "type": "p", "children": [], "text": "\nStep 17: Turn on the compressor (See Figure O)." }

Step 18: Check for a steady mist from the Mouthpiece (See Figure P). If there is no mist, check all tubing connections and make sure that the compressor is working properly.

{ "type": "p", "children": [], "text": "\nStep 18: Check for a steady mist from the Mouthpiece (See Figure P). If there is no mist, check all tubing connections and make sure that the compressor is working properly." }

Step 19: Sit or stand in an upright position that will allow you to breathe normally. Place the Mouthpiece between your teeth and on top of your tongue and breathe normally only through your mouth (See Figure Q). Nose clips may help you breathe through your mouth and not through your nose. Do not block the airflow with your tongue.

{ "type": "p", "children": [], "text": "\nStep 19: Sit or stand in an upright position that will allow you to breathe normally. Place the Mouthpiece between your teeth and on top of your tongue and breathe normally only through your mouth (See Figure Q). Nose clips may help you breathe through your mouth and not through your nose. Do not block the airflow with your tongue." }

Step 20: Keep breathing in your tobramycin inhalation solution medicine for at least 15 minutes to get your full dose. Continue therapy until all your tobramycin inhalation solution medicine is gone, and there is no longer any mist being made. You may hear a sputtering sound coming from the Mouthpiece when the Nebulizer Cup is empty. The entire tobramycin inhalation solution therapy should take about 15 minutes to complete.

{ "type": "p", "children": [], "text": "\nStep 20: Keep breathing in your tobramycin inhalation solution medicine for at least 15 minutes to get your full dose. Continue therapy until all your tobramycin inhalation solution medicine is gone, and there is no longer any mist being made. You may hear a sputtering sound coming from the Mouthpiece when the Nebulizer Cup is empty. The entire tobramycin inhalation solution therapy should take about 15 minutes to complete." }

If you are interrupted, need to cough or rest during your tobramycin inhalation solution treatment, turn off the compressor to save your medicine. Turn the compressor back on when you are ready to restart your treatment.

{ "type": "p", "children": [], "text": "If you are interrupted, need to cough or rest during your tobramycin inhalation solution treatment, turn off the compressor to save your medicine. Turn the compressor back on when you are ready to restart your treatment." }

Follow the nebulizer cleaning and disinfecting instructions after completing your therapy.

{ "type": "p", "children": [], "text": "Follow the nebulizer cleaning and disinfecting instructions after completing your therapy." }

After your Tobramycin Inhalation Solution Inhalation Therapy

{ "type": "p", "children": [], "text": "\nAfter your Tobramycin Inhalation Solution Inhalation Therapy\n" }

Cleaning Your Nebulizer

{ "type": "p", "children": [], "text": "\nCleaning Your Nebulizer\n" }

To reduce the risk of infection, illness or injury from contamination, you must thoroughly clean all parts of the nebulizer as instructed after each treatment. Never use a nebulizer with a clogged nozzle. If the nozzle is clogged, no aerosol mist is made, and your therapy will not be as effective. Replace the nebulizer if clogging occurs.

{ "type": "p", "children": [], "text": "To reduce the risk of infection, illness or injury from contamination, you must thoroughly clean all parts of the nebulizer as instructed after each treatment. Never use a nebulizer with a clogged nozzle. If the nozzle is clogged, no aerosol mist is made, and your therapy will not be as effective. Replace the nebulizer if clogging occurs." }

1. Remove tubing from nebulizer and disassemble nebulizer parts.

{ "type": "p", "children": [], "text": "1. Remove tubing from nebulizer and disassemble nebulizer parts." }

2. Wash all parts (except tubing) with warm water and liquid dish soap.

{ "type": "p", "children": [], "text": "2. Wash all parts (except tubing) with warm water and liquid dish soap." }

3. Rinse thoroughly with warm water and shake out water.

{ "type": "p", "children": [], "text": "3. Rinse thoroughly with warm water and shake out water." }

4. Air dry or hand dry nebulizer parts on a clean, lint-free cloth. Reassemble nebulizer when dry, and store.

{ "type": "p", "children": [], "text": "4. Air dry or hand dry nebulizer parts on a clean, lint-free cloth. Reassemble nebulizer when dry, and store." }

You can also wash all parts of the nebulizer in a dishwasher (except tubing).

{ "type": "p", "children": [], "text": "You can also wash all parts of the nebulizer in a dishwasher (except tubing)." }

1. Place the nebulizer parts in a dishwasher basket.

{ "type": "p", "children": [], "text": "1. Place the nebulizer parts in a dishwasher basket." }

2. Place the dishwasher basket on the top rack of the dishwasher.

{ "type": "p", "children": [], "text": "2. Place the dishwasher basket on the top rack of the dishwasher." }

3. Remove and dry the parts when the cycle is complete.

{ "type": "p", "children": [], "text": "3. Remove and dry the parts when the cycle is complete." }

Disinfecting Your Nebulizer

{ "type": "p", "children": [], "text": "\nDisinfecting Your Nebulizer\n" }

Your nebulizer is for your use only. Do not share your nebulizer with other people. You must disinfect the nebulizer every other treatment day. Failure to disinfect the nebulizer every other treatment day could lead to serious or fatal illness.

{ "type": "p", "children": [], "text": "Your nebulizer is for your use only. Do not share your nebulizer with other people. You must disinfect the nebulizer every other treatment day. Failure to disinfect the nebulizer every other treatment day could lead to serious or fatal illness." }

Clean the nebulizer as described above. Every other treatment day, disinfect the nebulizer parts (except tubing) by boiling them in water for a full 10 minutes. Dry parts on a clean, lint-free cloth.

{ "type": "p", "children": [], "text": "Clean the nebulizer as described above. Every other treatment day, disinfect the nebulizer parts (except tubing) by boiling them in water for a full 10 minutes. Dry parts on a clean, lint-free cloth." }

Care and Use of Your Pulmo-Aide® Compressor

{ "type": "p", "children": [], "text": "\nCare and Use of Your Pulmo-Aide® Compressor\n" }

Follow the manufacturer instructions for care and use of your compressor.

{ "type": "p", "children": [], "text": "Follow the manufacturer instructions for care and use of your compressor." }

Filter Change:

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

{ "type": "ul", "children": [ "DeVilbiss Compressor filters should be changed every six months or sooner if the filter turns completely gray in color." ], "text": "" }

Compressor Cleaning:

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

{ "type": "ul", "children": [ "With power switch in the \"Off\" position, unplug power cord from wall outlet.", "Wipe outside of the compressor cabinet with a clean, damp cloth every few days to keep dust free." ], "text": "" }

Caution: Do not submerge in water because this will damage the compressor.

{ "type": "p", "children": [], "text": "\nCaution: Do not submerge in water because this will damage the compressor." }

How should I store tobramycin inhalation solution?

{ "type": "p", "children": [], "text": "\nHow should I store tobramycin inhalation solution?\n" }

{ "type": "ul", "children": [ "Store tobramycin inhalation solution ampules in a refrigerator between 36°F to 46°F (2°C to 8°C) until needed.", "You may store the tobramycin inhalation solution ampules in the foil pouches (opened or unopened) at room temperature 77°F (25°C) for up to 28 days.", "\nDo not use tobramycin inhalation solution ampules if they have been stored at room temperature for more than 28 days.", "Protect tobramycin inhalation solution ampules from light." ], "text": "" }

Keep tobramycin inhalation solution and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep tobramycin inhalation solution and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Additional Information

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

Nebulizer: 1-800-327-8632

{ "type": "p", "children": [], "text": "Nebulizer: 1-800-327-8632" }

Compressor: 1-800-338-1988

{ "type": "p", "children": [], "text": "Compressor: 1-800-338-1988" }

Tobramycin Inhalation Solution: 1-800-399-2561

{ "type": "p", "children": [], "text": "Tobramycin Inhalation Solution: 1-800-399-2561" }

®The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

{ "type": "p", "children": [], "text": "\n®The other brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products." }

Manufactured for:

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

Lupin Pharmaceuticals, Inc.

{ "type": "p", "children": [], "text": "\nLupin Pharmaceuticals, Inc.\n" }

Naples, FL 34108

{ "type": "p", "children": [], "text": "Naples, FL 34108" }

United States

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

Revised: July 2025

{ "type": "p", "children": [], "text": "Revised: July 2025" }

Pouch Label

{ "type": "p", "children": [], "text": "\nPouch Label " }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only " }

NDC 68180-962-04

{ "type": "p", "children": [], "text": "NDC 68180-962-04" }

Tobramycin Inhalation Solution, USP

{ "type": "p", "children": [], "text": "Tobramycin Inhalation Solution, USP" }

300 mg / 5 mL Ampules

{ "type": "p", "children": [], "text": "300 mg / 5 mL Ampules" }

Store in Refrigerator

{ "type": "p", "children": [], "text": "Store in Refrigerator" }

Carton Label

{ "type": "p", "children": [], "text": "\nCarton Label" }

Rx Only

{ "type": "p", "children": [], "text": "Rx Only " }

NDC 68180-962-56

{ "type": "p", "children": [], "text": "NDC 68180-962-56" }

Tobramycin Inhalation Solution, USP

{ "type": "p", "children": [], "text": "Tobramycin Inhalation Solution, USP" }

300 mg / 5 mL Ampules

{ "type": "p", "children": [], "text": "300 mg / 5 mL Ampules" }

56 Single-Use Ampules (28-Day Supply) (4 Single-Use Ampules per pouch, 14 pouches per carton)

{ "type": "p", "children": [], "text": "56 Single-Use Ampules (28-Day Supply) (4 Single-Use Ampules per pouch, 14 pouches per carton)" }

STORE IN REFRIGERATOR

{ "type": "p", "children": [], "text": "STORE IN REFRIGERATOR" }

TOBI Podhaler is indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa.

{ "type": "p", "children": [], "text": "TOBI Podhaler is indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa." }

Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV1) <25% or >80% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14)].

{ "type": "p", "children": [], "text": "Safety and efficacy have not been demonstrated in patients under the age of 6 years, patients with forced expiratory volume in 1 second (FEV1) <25% or >80% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14)]." }

DO NOT SWALLOW TOBI PODHALER CAPSULES

{ "type": "p", "children": [], "text": "DO NOT SWALLOW TOBI PODHALER CAPSULES" }

FOR USE WITH THE PODHALER DEVICE ONLY

{ "type": "p", "children": [], "text": "FOR USE WITH THE PODHALER DEVICE ONLY" }

FOR ORAL INHALATION ONLY

{ "type": "p", "children": [], "text": "FOR ORAL INHALATION ONLY " }

TOBI Podhaler capsules must not be swallowed as the intended effects in the lungs will not be obtained. The contents of TOBI Podhaler capsules are only for oral inhalation and should only be used with the Podhaler device.

{ "type": "p", "children": [], "text": "TOBI Podhaler capsules must not be swallowed as the intended effects in the lungs will not be obtained. The contents of TOBI Podhaler capsules are only for oral inhalation and should only be used with the Podhaler device." }

The recommended dosage of TOBI Podhaler for both adults and pediatric patients 6 years of age and older is the inhalation of the contents of four 28 mg TOBI Podhaler capsules twice-daily for 28 days using the Podhaler device.

{ "type": "p", "children": [], "text": "The recommended dosage of TOBI Podhaler for both adults and pediatric patients 6 years of age and older is the inhalation of the contents of four 28 mg TOBI Podhaler capsules twice-daily for 28 days using the Podhaler device. " }

Refer to the Instructions For Use (IFU) for full administration information.

{ "type": "p", "children": [], "text": "Refer to the Instructions For Use (IFU) for full administration information." }

Dosage is not adjusted by weight. Each dose of four capsules should be taken as close to 12 hours apart as possible; each dose should not be taken less than 6 hours apart.

{ "type": "p", "children": [], "text": "Dosage is not adjusted by weight. Each dose of four capsules should be taken as close to 12 hours apart as possible; each dose should not be taken less than 6 hours apart." }

TOBI Podhaler is administered twice-daily in alternating periods of 28 days. After 28 days of therapy, patients should stop TOBI Podhaler therapy for the next 28 days, and then resume therapy for the next 28-day on and 28-day off cycle.

{ "type": "p", "children": [], "text": "TOBI Podhaler is administered twice-daily in alternating periods of 28 days. After 28 days of therapy, patients should stop TOBI Podhaler therapy for the next 28 days, and then resume therapy for the next 28-day on and 28-day off cycle. " }

TOBI Podhaler capsules should always be stored in the blister and each capsule should only be removed IMMEDIATELY BEFORE USE.

{ "type": "p", "children": [], "text": "TOBI Podhaler capsules should always be stored in the blister and each capsule should only be removed IMMEDIATELY BEFORE USE." }

For patients taking several different inhaled medications and/or performing chest physiotherapy, the order of therapies should follow the physician’s recommendation. It is recommended that TOBI Podhaler is taken last.

{ "type": "p", "children": [], "text": "For patients taking several different inhaled medications and/or performing chest physiotherapy, the order of therapies should follow the physician’s recommendation. It is recommended that TOBI Podhaler is taken last." }

Inhalation powder:

{ "type": "p", "children": [], "text": "Inhalation powder:" }

28 mg: clear, colorless hypromellose capsule with “MYL TPH” in blue radial imprint on one part of the capsule and the Mylan logo in blue radial imprint on the other part of the capsule.

{ "type": "p", "children": [], "text": "28 mg: clear, colorless hypromellose capsule with “MYL TPH” in blue radial imprint on one part of the capsule and the Mylan logo in blue radial imprint on the other part of the capsule." }

TOBI Podhaler is contraindicated in patients with a known hypersensitivity to any aminoglycoside.

{ "type": "p", "children": [], "text": "TOBI Podhaler is contraindicated in patients with a known hypersensitivity to any aminoglycoside." }

Bronchospasm has been reported with inhalation of TOBI Podhaler [see Adverse Reactions (6.1)]. Bronchospasm should be treated as medically appropriate.

Ototoxicity with use of TOBI Podhaler

Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected auditory or vestibular dysfunction.

Ototoxicity, as measured by complaints of hearing loss or tinnitus, was reported by patients in the TOBI Podhaler clinical studies [seeAdverse Reactions (6.1)]. Tinnitus may be a sentinel symptom of ototoxicity, and therefore the onset of this symptom warrants caution. Ototoxicity, manifested as both auditory (hearing loss) and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness.

Risk of Ototoxicity Due to Mitochondrial DNA Variants

Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene (MT-RNR1), particularly the m.1555A>G variant. Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range. Mitochondrial DNA variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown. In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies.

Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected renal dysfunction.

Nephrotoxicity was not observed during TOBI Podhaler clinical studies but has been associated with aminoglycosides as a class.

Caution should be exercised when prescribing TOBI Podhaler to patients with known or suspected neuromuscular dysfunction.

TOBI Podhaler should be used cautiously in patients with neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease, since aminoglycosides may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function.

Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. Patients who use TOBI Podhaler during pregnancy, or become pregnant while taking TOBI Podhaler should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

Patients receiving concomitant TOBI and parenteral aminoglycoside therapy should be monitored as clinically appropriate for toxicities associated with aminoglycosides as a class. Serum tobramycin levels should be monitored.

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.

TOBI Podhaler has been evaluated for safety in 425 cystic fibrosis patients exposed to at least one dose of TOBI Podhaler, including 273 patients who were exposed across three cycles (6 months) of treatment. Each cycle consisted of 28 days on-treatment (with 112 mg administered twice-daily) and 28 days off-treatment. Patients with serum creatinine ≥2 mg/dL and blood urea nitrogen (BUN) ≥40 mg/dL were excluded from clinical studies. There were 218 males and 207 females in this population, and reflecting the cystic fibrosis population in the U.S., the vast majority of patients were Caucasian. There were 221 patients ≥20 years old, 121 patients ≥13 to <20 years old, and 83 patients ≥6 to <13 years old. There were 239 patients with screening FEV1 % predicted ≥50%, 156 patients with screening FEV1 % predicted <50%, and 30 patients with missing FEV1 % predicted.

The primary safety population reflects patients from Study 1, an open-label study comparing TOBI Podhaler with TOBI (tobramycin inhalation solution, USP) over three cycles of 4 weeks on treatment followed by 4 weeks off treatment. Randomization, in a planned 3:2 ratio, resulted in 308 patients treated with TOBI Podhaler and 209 patients treated with TOBI. For both the TOBI Podhaler and TOBI groups, mean exposure to medication for each cycle was 28 to 29 days. The mean age for both arms was between 25 and 26 years old. The mean baseline FEV1 % predicted for both arms was 53%.

Table 1 displays adverse drug reactions reported by at least 2% of TOBI Podhaler patients in Study 1, inclusive of all cycles (on and off treatment). Adverse drug reactions are listed according to MedDRA system organ class and sorted within system organ class group in descending order of frequency.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Adverse Reactions Reported in Study 1 (Occurring in ≥2% of TOBI Podhaler Patients)</span> </caption> <col width="58%"/> <col width="21%"/> <col width="21%"/> <tfoot> <tr> <td align="left" colspan="3"> <dl class="Footnote"> <dt> <a href="#footnote-reference-1" name="footnote-1">*</a> </dt> <dd>This includes adverse events of pulmonary or cystic fibrosis exacerbations</dd> </dl> </td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">Primary System Organ Class</span> <br/>Preferred Term</p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">TOBI Podhaler</span> <br/> <span class="Bold">N=308</span> <br/> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Toprule" valign="top"> <p class="First"> <span class="Bold">TOBI</span> <br/> <span class="Bold">N=209</span> <br/> <span class="Bold">%</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Respiratory, thoracic, and mediastinal disorders</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Cough </p> </td><td align="center" valign="top"> <p class="First">48.4</p> </td><td align="center" valign="top"> <p class="First">31.1</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Lung disorder<a class="Sup" href="#footnote-1" name="footnote-reference-1">*</a> </p> </td><td align="center" valign="top"> <p class="First">33.8</p> </td><td align="center" valign="top"> <p class="First">30.1</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Productive cough</p> </td><td align="center" valign="top"> <p class="First">18.2</p> </td><td align="center" valign="top"> <p class="First">19.6</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Dyspnea</p> </td><td align="center" valign="top"> <p class="First">15.6</p> </td><td align="center" valign="top"> <p class="First">12.4</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Oropharyngeal pain</p> </td><td align="center" valign="top"> <p class="First">14.0</p> </td><td align="center" valign="top"> <p class="First">10.5</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Dysphonia</p> </td><td align="center" valign="top"> <p class="First">13.6</p> </td><td align="center" valign="top"> <p class="First">3.8</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Hemoptysis</p> </td><td align="center" valign="top"> <p class="First">13.0</p> </td><td align="center" valign="top"> <p class="First">12.4</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Nasal congestion</p> </td><td align="center" valign="top"> <p class="First">8.1</p> </td><td align="center" valign="top"> <p class="First">7.2</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Rales</p> </td><td align="center" valign="top"> <p class="First">7.1</p> </td><td align="center" valign="top"> <p class="First">6.2</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Wheezing</p> </td><td align="center" valign="top"> <p class="First">6.8</p> </td><td align="center" valign="top"> <p class="First">6.2</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Chest discomfort</p> </td><td align="center" valign="top"> <p class="First">6.5</p> </td><td align="center" valign="top"> <p class="First">2.9</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Throat irritation</p> </td><td align="center" valign="top"> <p class="First">4.5</p> </td><td align="center" valign="top"> <p class="First">1.9</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Gastrointestinal disorders</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Nausea</p> </td><td align="center" valign="top"> <p class="First">7.5</p> </td><td align="center" valign="top"> <p class="First">9.6</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Vomiting</p> </td><td align="center" valign="top"> <p class="First">6.2</p> </td><td align="center" valign="top"> <p class="First">5.7</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Diarrhea</p> </td><td align="center" valign="top"> <p class="First">4.2</p> </td><td align="center" valign="top"> <p class="First">1.9</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Dysgeusia</p> </td><td align="center" valign="top"> <p class="First">3.9</p> </td><td align="center" valign="top"> <p class="First">0.5</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Infections and infestations</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Upper respiratory tract infection</p> </td><td align="center" valign="top"> <p class="First">6.8</p> </td><td align="center" valign="top"> <p class="First">8.6</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Investigations</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Pulmonary function test decreased</p> </td><td align="center" valign="top"> <p class="First">6.8</p> </td><td align="center" valign="top"> <p class="First">8.1</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Forced expiratory volume decreased</p> </td><td align="center" valign="top"> <p class="First">3.9</p> </td><td align="center" valign="top"> <p class="First">1.0</p> </td> </tr> <tr> <td valign="top"> <p class="First">     Blood glucose increased</p> </td><td align="center" valign="top"> <p class="First">2.9</p> </td><td align="center" valign="top"> <p class="First">0.5</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Vascular disorders</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Epistaxis</p> </td><td align="center" valign="top"> <p class="First">2.6</p> </td><td align="center" valign="top"> <p class="First">1.9</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Nervous system disorders</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Headache</p> </td><td align="center" valign="top"> <p class="First">11.4</p> </td><td align="center" valign="top"> <p class="First">12.0</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">General disorders and administration site conditions</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Pyrexia</p> </td><td align="center" valign="top"> <p class="First">15.6</p> </td><td align="center" valign="top"> <p class="First">12.4</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Musculoskeletal and connective tissue disorders</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr> <td valign="top"> <p class="First">     Musculoskeletal chest pain</p> </td><td align="center" valign="top"> <p class="First">4.5</p> </td><td align="center" valign="top"> <p class="First">4.8</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Skin and subcutaneous tissue disorders</span> </p> </td><td valign="top"></td><td valign="top"></td> </tr> <tr class="Last"> <td class="Botrule" valign="top"> <p class="First">     Rash</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">2.3</p> </td><td align="center" class="Botrule" valign="top"> <p class="First">2.4</p> </td> </tr> </tbody> </table></div>

Adverse drug reactions that occurred in <2% of patients treated with TOBI Podhaler in Study 1 were: bronchospasm (TOBI Podhaler 1.6%, TOBI 0.5%); deafness including deafness unilateral (reported as mild to moderate hearing loss or increased hearing loss) (TOBI Podhaler 1.0%, TOBI 0.5%); and tinnitus (TOBI Podhaler 1.9%, TOBI 2.4%).

Discontinuations in Study 1 were higher in the TOBI Podhaler arm compared to TOBI (27% TOBI Podhaler versus 18% TOBI). This was driven primarily by discontinuations due to adverse events (14% TOBI Podhaler versus 8% TOBI). Higher rates of discontinuation were seen in subjects ≥20 years old and those with baseline FEV1 % predicted <50%.

Respiratory related hospitalizations occurred in 24% of the patients in the TOBI Podhaler arm and 22% of the patients in the TOBI arm. There was an increased new usage of antipseudomonal medication in the TOBI Podhaler arm (65% TOBI Podhaler versus 55% TOBI). This included oral antibiotics in 55% of TOBI Podhaler patients and 40% of TOBI patients and intravenous antibiotics in 35% of TOBI Podhaler patients and 33% of TOBI patients. Median time to first antipseudomonal usage was 89 days in the TOBI Podhaler arm and 112 days in the TOBI arm.

The supportive safety population reflects patients from two studies: Study 2, a double-blind, placebo-controlled design for the first treatment cycle, followed by all patients receiving TOBI Podhaler (replaced placebo) for two additional cycles, and Study 3, a double-blind, placebo-controlled trial for one treatment cycle only. Placebo in these studies was inhaled powder without the active ingredient, tobramycin. The patient population for these studies was much younger than in Study 1 (mean age 13 years old).

Adverse drug reactions reported more frequently by TOBI Podhaler patients in the placebo-controlled cycle (Cycle 1) of Study 2, which included 46 TOBI Podhaler and 49 placebo patients, were:

Respiratory, thoracic, and mediastinal disorders

Pharyngolaryngeal pain (TOBI Podhaler 10.9%, placebo 0%); dysphonia (TOBI Podhaler 4.3%, placebo 0%)

Gastrointestinal disorders

Dysgeusia (TOBI Podhaler 6.5%, placebo 2.0%)

Adverse drug reactions reported more frequently by TOBI Podhaler patients in Study 3, which included 30 TOBI Podhaler and 32 placebo patients, were:

Respiratory, thoracic, and mediastinal disorders

Cough (TOBI Podhaler 10%, placebo 0%)

Ear and labyrinth disorders

Hypoacusis (TOBI Podhaler 10%, placebo 6.3%)

In Study 1, audiology testing was performed in a subset of approximately 25% of TOBI Podhaler (n=78) and TOBI (n=45) patients. Using the criteria for either ear of ≥10 dB loss at two consecutive frequencies, ≥20 dB loss at any frequency, or loss of response at three consecutive frequencies where responses were previously obtained, five TOBI Podhaler patients and three TOBI patients were judged to have ototoxicity, a ratio similar to the planned 3:2 randomization for this study.

Audiology testing was also performed in a subset of patients in both Study 2 (n=13 from the TOBI Podhaler group and n=9 from the placebo group) and Study 3 (n=14 from the TOBI Podhaler group and n=11 from the placebo group). In Study 2, no patients reported hearing complaints but two TOBI Podhaler patients met the criteria for ototoxicity. In Study 3, three TOBI Podhaler and two placebo patients had reports of ‘hypoacusis.’ One TOBI Podhaler and two placebo patients met the criteria for ototoxicity. In some patients, ototoxicity was transient or may have been related to a conductive defect.

Cough is a common symptom in cystic fibrosis, reported in 42% of the patients in Study 1 at baseline. Cough was the most frequently reported adverse event in Study 1 and was more common in the TOBI Podhaler arm (48% TOBI Podhaler versus 31 % TOBI). There was a higher rate of cough adverse event reporting during the first week of active treatment with TOBI Podhaler (i.e., the first week of Cycle 1). The time to first cough event in the TOBI Podhaler and TOBI groups were similar thereafter. In some patients, cough resulted in discontinuation of TOBI Podhaler treatment. Sixteen patients (5%) receiving treatment with TOBI Podhaler discontinued study treatment due to cough events compared with 2 (1%) in the TOBI treatment group. Children and adolescents coughed more than adults when treated with TOBI Podhaler, yet the adults were more likely to discontinue: of the 16 patients on TOBI Podhaler in Study 1 who discontinued treatment due to cough events, 14 were ≥20 years of age, one patient was between the ages of 13 and <20, and one was between the ages of 6 and <13. The rates of bronchospasm (as measured by ≥20% decrease in FEV1 % predicted post-dose) were approximately 5% in both treatment groups, and none of these patients experienced concomitant cough.

In Study 2, cough was the most commonly reported adverse event during the first cycle of treatment (the double blind period of treatment) and occurred more frequently in placebo-treated patients (26.5%) than patients treated with TOBI Podhaler (13%). Similar percentages of patients in both treatment groups reported cough as a baseline symptom. In Study 3, cough events were reported by three patients in the TOBI Podhaler group (10%) and none in the placebo group (0%).

The following adverse reactions have been identified during postapproval use of TOBI Podhaler. 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.

Respiratory, thoracic, and mediastinal disorders

Aphonia, Sputum discolored

General disorders and administration site conditions

Malaise

No clinical drug interaction studies have been performed with TOBI Podhaler. In clinical studies, patients receiving TOBI Podhaler continued to take dornase alfa, bronchodilators, inhaled corticosteroids, and macrolides. No clinical signs of drug interactions with these medicines were identified.

{ "type": "p", "children": [], "text": "No clinical drug interaction studies have been performed with TOBI Podhaler. In clinical studies, patients receiving TOBI Podhaler continued to take dornase alfa, bronchodilators, inhaled corticosteroids, and macrolides. No clinical signs of drug interactions with these medicines were identified." }

Concurrent and/or sequential use of TOBI Podhaler with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided.

{ "type": "p", "children": [], "text": "Concurrent and/or sequential use of TOBI Podhaler with other drugs with neurotoxic, nephrotoxic, or ototoxic potential should be avoided." }

Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. TOBI Podhaler should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and TOBI Podhaler has not been evaluated.

{ "type": "p", "children": [], "text": "Some diuretics can enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. TOBI Podhaler should not be administered concomitantly with ethacrynic acid, furosemide, urea, or intravenous mannitol. The interaction between inhaled mannitol and TOBI Podhaler has not been evaluated. " }

Aminoglycosides can cause fetal harm. Published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [Warnings and Precautions (5.5)]. Although there are no available data on TOBI Podhaler use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. There are risks to the mother associated with cystic fibrosis in pregnancy (see Clinical Considerations). In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis there were no adverse developmental outcomes; however, ototoxicity was not evaluated in the offspring from these studies (see Data). Advise pregnant women of the potential risk to a fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations are 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/or Embryo/Fetal Risk

Cystic fibrosis may increase the risk for preterm delivery.

No reproduction toxicology studies have been conducted with TOBI Podhaler. However, subcutaneous administration of tobramycin at doses of up to 100 (rat) or 20 (rabbit) mg/kg/day during organogenesis was not associated with adverse developmental outcomes. Doses of tobramycin ≥40 mg/kg/day were severely maternally toxic to rabbits and precluded the evaluation of adverse developmental outcomes. Ototoxicity was not evaluated in offspring during non-clinical reproductive toxicity studies with tobramycin.

There are no data on the presence of tobramycin following administration of TOBI Podhaler in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. Limited published data on other formulations of tobramycin in lactating women indicate that tobramycin is present in human milk. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. Tobramycin may cause alteration in the intestinal flora of the breastfeeding infant (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TOBI Podhaler and any potential adverse effects on the breastfed infant from TOBI Podhaler or from the underlying maternal condition.

Tobramycin may cause intestinal flora alteration. Advise a woman to monitor the breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).

Patients 6 years and older were included in the Phase 3 studies with TOBI Podhaler; 206 patients below 20 years of age received TOBI Podhaler. No dosage adjustments are needed based on age. The overall pattern of adverse events in pediatric patients was similar to the adults. Dysgeusia (taste disturbance) was more commonly reported in younger patients six to 19 years of age than in patients 20 years and older, 7.4% versus 2.7%, respectively. Safety and effectiveness in pediatric patients below the age of 6 years have not been established.

Clinical studies of TOBI Podhaler did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Tobramycin is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function [see Warnings and Precautions (5.2, 5.5)].

Tobramycin is primarily excreted unchanged in the urine and renal function is expected to affect the exposure to tobramycin. The risk of adverse reactions to this drug may be greater in patients with impaired renal function. Patients with serum creatinine ≥2 mg/dL and blood urea nitrogen (BUN) ≥40 mg/dL have not been included in clinical studies and there are no data in this population to support a recommendation regarding dose adjustment with TOBI Podhaler [see Warnings and Precautions (5.2, 5.5)].

No studies have been performed in patients with hepatic impairment. As tobramycin is not metabolized, an effect of hepatic impairment on the exposure to tobramycin is not expected.

Adequate data do not exist for the use of TOBI Podhaler in patients after organ transplantation.

The maximum tolerated daily dose of TOBI Podhaler has not been established.

{ "type": "p", "children": [], "text": "The maximum tolerated daily dose of TOBI Podhaler has not been established." }

In the event of accidental oral ingestion of TOBI Podhaler capsules, systemic toxicity is unlikely as tobramycin is poorly absorbed. Tobramycin serum concentrations may be helpful in monitoring overdosage.

{ "type": "p", "children": [], "text": "In the event of accidental oral ingestion of TOBI Podhaler capsules, systemic toxicity is unlikely as tobramycin is poorly absorbed. Tobramycin serum concentrations may be helpful in monitoring overdosage." }

Acute toxicity should be treated with immediate withdrawal of TOBI Podhaler, and baseline tests of renal function should be undertaken.

{ "type": "p", "children": [], "text": "Acute toxicity should be treated with immediate withdrawal of TOBI Podhaler, and baseline tests of renal function should be undertaken." }

Hemodialysis may be helpful in removing tobramycin from the body.

{ "type": "p", "children": [], "text": "Hemodialysis may be helpful in removing tobramycin from the body." }

In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered.

{ "type": "p", "children": [], "text": "In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment. In the case of any overdosage, the possibility of drug interactions with alterations in drug disposition should be considered." }

TOBI Podhaler consists of a dry powder formulation of tobramycin for oral inhalation only with the Podhaler device. The inhalation powder is filled into clear, colorless hypromellose capsules.

{ "type": "p", "children": [], "text": "TOBI Podhaler consists of a dry powder formulation of tobramycin for oral inhalation only with the Podhaler device. The inhalation powder is filled into clear, colorless hypromellose capsules." }

Each clear, colorless hypromellose capsule contains a spray dried powder of 28 mg of tobramycin active ingredient with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment).

{ "type": "p", "children": [], "text": "Each clear, colorless hypromellose capsule contains a spray dried powder of 28 mg of tobramycin active ingredient with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment)." }

The active component of TOBI Podhaler is tobramycin. Tobramycin is an aminoglycoside antibiotic. Its chemical name is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine; its structural formula is:

{ "type": "p", "children": [], "text": "The active component of TOBI Podhaler is tobramycin. Tobramycin is an aminoglycoside antibiotic. Its chemical name is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl-(1→6)]-2-deoxy-L-streptamine; its structural formula is:" }

Tobramycin has a molecular weight of 467.52, and its empirical formula is C18H37N5O9. Tobramycin is a white to almost white powder; visually free from any foreign contaminants. Tobramycin is freely soluble in water, very slightly soluble in ethanol, and practically insoluble in chloroform and ether.

{ "type": "p", "children": [], "text": "Tobramycin has a molecular weight of 467.52, and its empirical formula is C18H37N5O9. Tobramycin is a white to almost white powder; visually free from any foreign contaminants. Tobramycin is freely soluble in water, very slightly soluble in ethanol, and practically insoluble in chloroform and ether." }

The Podhaler device is a plastic device used to inhale the dry powder contained in the TOBI Podhaler capsule. Under standardized in vitro testing at a fixed flow rate of 60 L/min and volume of 2 L for 2 seconds, the Podhaler device has a target delivered dose of 102 mg of tobramycin from the mouthpiece (4 capsules per dose). Peak inspiratory flow rate and inhaled volumes were explored in 96 cystic fibrosis patients aged 6 years and older. Older patients with significant disease progression and associated decreases in forced expiratory volume (FEV1) and younger patients with inhaled volumes <1 L were able to generate inspiratory flow rates and volumes required to receive their medication when following the instructions for use. However, no pediatric patients aged 6 to 10 years with FEV1 less than 40% predicted were evaluated.

{ "type": "p", "children": [], "text": "The Podhaler device is a plastic device used to inhale the dry powder contained in the TOBI Podhaler capsule. Under standardized in vitro testing at a fixed flow rate of 60 L/min and volume of 2 L for 2 seconds, the Podhaler device has a target delivered dose of 102 mg of tobramycin from the mouthpiece (4 capsules per dose). Peak inspiratory flow rate and inhaled volumes were explored in 96 cystic fibrosis patients aged 6 years and older. Older patients with significant disease progression and associated decreases in forced expiratory volume (FEV1) and younger patients with inhaled volumes <1 L were able to generate inspiratory flow rates and volumes required to receive their medication when following the instructions for use. However, no pediatric patients aged 6 to 10 years with FEV1 less than 40% predicted were evaluated." }

Tobramycin is an aminoglycoside antibacterial [see Clinical Pharmacology (12.4)].

TOBI Podhaler contains tobramycin, a cationic polar molecule that does not readily cross epithelial membranes. TOBI Podhaler is specifically formulated for administration by oral inhalation. The systemic exposure to tobramycin after inhalation of TOBI Podhaler is expected to result from pulmonary absorption of the dose fraction delivered to the lungs as tobramycin and is not absorbed to any appreciable extent when administered via the oral route.

After inhalation of a 112 mg single dose (4 times 28 mg capsules) of TOBI Podhaler in cystic fibrosis patients, the maximum serum concentration (Cmax) of tobramycin was 1.02 ± 0.53 mcg/mL (mean ± SD) and the median time to reach the peak concentration (Tmax) was 1 hour. In comparison, after inhalation of a single 300 mg dose of TOBI, Cmax was 1.04 ± 0.58 mcg/mL and median Tmax was 1 hour. The extent of systemic exposure (AUC0-12) was also similar: 4.6 ± 2.0 mcg∙h/mL following the 112 mg TOBI Podhaler dose and 4.8 ± 2.5 mcg∙h/mL following the 300 mg TOBI dose. At the end of a 4-week dosing cycle of TOBI Podhaler (112 mg twice-daily), the maximum serum concentration of tobramycin 1 hour after dosing ranged from 1.48 ± 0.69 mcg/mL to 1.99 ± 0.59 mcg/mL (mean ± SD).

After inhalation of a 112 mg single dose (4 times 28 mg capsules) of TOBI Podhaler in cystic fibrosis patients, sputum Cmax of tobramycin was 1048 ± 1080 mcg/g (mean ± SD). In comparison, after inhalation of a single 300 mg dose of TOBI, sputum Cmax was 737 ± 1028 mcg/g. The variability in pharmacokinetic parameters was higher in sputum as compared to serum.

A population pharmacokinetic analysis for TOBI Podhaler in cystic fibrosis patients estimated the apparent volume of distribution of tobramycin in the central compartment to be 85.1 L for a typical cystic fibrosis (CF) patient.

Binding of tobramycin to serum proteins is negligible.

Tobramycin is not metabolized and is primarily excreted unchanged in the urine.

Tobramycin is eliminated from the systemic circulation primarily by glomerular filtration of the unchanged compound. Systemically absorbed tobramycin following TOBI Podhaler administration is also expected to be eliminated principally by glomerular filtration.

The apparent terminal half-life of tobramycin in serum after inhalation of a 112 mg single dose of TOBI Podhaler was approximately 3 hours in cystic fibrosis patients and consistent with the half-life of tobramycin after TOBI inhalation.

A population pharmacokinetic analysis for TOBI Podhaler in cystic fibrosis patients aged 6 to 58 years estimated the apparent serum clearance of tobramycin to be 14.5 L/h. No clinically relevant covariates that were predictive of tobramycin clearance were identified from this analysis.

Tobramycin is an aminoglycoside antibacterial produced by Streptomyces tenebrarius. It acts primarily by disrupting protein synthesis leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death.

Tobramycin has in vitro activity against Gram-negative bacteria including P. aeruginosa. It is bactericidal in vitro at peak concentrations equal to or slightly greater than the minimum inhibitory concentration (MIC).

Interpretive criteria for inhaled antibacterial products are not defined. The in vitro antimicrobial susceptibility test methods used to determine the susceptibility for parenteral tobramycin therapy can be used to monitor the susceptibility of P. aeruginosa isolated from cystic fibrosis patients. (1,2,3) The relationship between in vitro susceptibility test results and clinical outcome with TOBI Podhaler therapy is not clear. A single sputum sample from a cystic fibrosis patient may contain multiple morphotypes of P. aeruginosa and each morphotype may require a different concentration of tobramycin to inhibit its growth in vitro. Patients should be monitored for changes in tobramycin susceptibility.

In clinical studies, some increases from baseline to the end of the treatment period were observed in the tobramycin MIC for P. aeruginosa morphotypes. In general, a higher percentage of patients treated with TOBI Podhaler had increases in tobramycin MIC compared with placebo or patients treated with TOBI inhalation solution.

The clinical significance of changes in MICs for P. aeruginosa has not been clearly established in the treatment of cystic fibrosis patients.

Some emerging resistance to aztreonam, ceftazidime, ciprofloxacin, imipenem, or meropenem were observed in the TOBI Podhaler clinical trials. As other anti-pseudomonal antibiotics were concomitantly utilized in many patients in the clinical trials, the association with TOBI Podhaler is not clear.

No trends were observed in the isolation of treatment-emergent bacterial respiratory pathogens (Burkholderia cepacia, Stenotrophomonas maltophilia, Staphylococcus aureus, and Achromobacter xylosoxidans).

Carcinogenicity studies were not conducted with TOBI Podhaler. A 2-year rat inhalation toxicology study to assess carcinogenic potential of TOBI (tobramycin inhalation solution, USP) has been completed. Rats were exposed to TOBI for up to 1.5 hours per day for 95 weeks. Serum levels of tobramycin of up to 35 mcg/mL were measured in rats, in contrast to the maximum 1.99 ± 0.59 mcg/mL level observed in cystic fibrosis patients in TOBI Podhaler clinical trials. There was no drug-related increase in the incidence of any variety of tumor.

Additionally, tobramycin has been evaluated for genotoxicity in a battery of in vitro and in vivo tests. The Ames bacterial reversion test, conducted with 5 tester strains, failed to show a significant increase in revertants with or without metabolic activation in all strains. Tobramycin was negative in the mouse lymphoma forward mutation assay, did not induce chromosomal aberrations in Chinese hamster ovary cells, and was negative in the mouse micronucleus test.

Subcutaneous administration of up to 100 mg/kg of tobramycin did not affect mating behavior or cause impairment of fertility in male or female rats.

The Phase 3 clinical development program included two placebo-controlled studies (Studies 2 and 3) and one open-label study (Study 1), which randomized and dosed 157 and 517 patients, respectively, with a clinical diagnosis of cystic fibrosis, confirmed by quantitative pilocarpine iontophoresis sweat chloride test, well-characterized disease causing mutations in each CFTR gene, or abnormal nasal transepithelial potential difference characteristic of cystic fibrosis.

{ "type": "p", "children": [], "text": "The Phase 3 clinical development program included two placebo-controlled studies (Studies 2 and 3) and one open-label study (Study 1), which randomized and dosed 157 and 517 patients, respectively, with a clinical diagnosis of cystic fibrosis, confirmed by quantitative pilocarpine iontophoresis sweat chloride test, well-characterized disease causing mutations in each CFTR gene, or abnormal nasal transepithelial potential difference characteristic of cystic fibrosis. " }

In the placebo-controlled studies, all patients were aged between 6 and 21 years old and had an FEV1 at screening within the range of 25% to 80% (inclusive) of predicted normal values for their age, sex, and height based upon Knudson criteria. In addition, all patients were infected with P. aeruginosa as demonstrated by a positive sputum or throat culture (or bronchoalveolar lavage) within 6 months prior to screening, and also in a sputum culture taken at the screening visit. Among the 76 patients treated with TOBI Podhaler, 37% were males and 63% were females. Thirty-six patients were between 6 and 12 years of age, and 40 patients were between 13 and 21 years of age. Patients had a mean baseline FEV1 of 56% of predicted normal value.

{ "type": "p", "children": [], "text": "In the placebo-controlled studies, all patients were aged between 6 and 21 years old and had an FEV1 at screening within the range of 25% to 80% (inclusive) of predicted normal values for their age, sex, and height based upon Knudson criteria. In addition, all patients were infected with P. aeruginosa as demonstrated by a positive sputum or throat culture (or bronchoalveolar lavage) within 6 months prior to screening, and also in a sputum culture taken at the screening visit. Among the 76 patients treated with TOBI Podhaler, 37% were males and 63% were females. Thirty-six patients were between 6 and 12 years of age, and 40 patients were between 13 and 21 years of age. Patients had a mean baseline FEV1 of 56% of predicted normal value." }

In both studies, >90% of patients received concomitant therapies for cystic fibrosis-related indications. The most frequently used other antibacterial drugs (any route of administration) were azithromycin, ciprofloxacin, and ceftazidime. Consistent with the population of cystic fibrosis patients, the most frequently used concomitant medications included oral pancreatic enzyme preparations, mucolytics (especially dornase alfa), and selective β2-adrenoreceptor agonists.

{ "type": "p", "children": [], "text": "In both studies, >90% of patients received concomitant therapies for cystic fibrosis-related indications. The most frequently used other antibacterial drugs (any route of administration) were azithromycin, ciprofloxacin, and ceftazidime. Consistent with the population of cystic fibrosis patients, the most frequently used concomitant medications included oral pancreatic enzyme preparations, mucolytics (especially dornase alfa), and selective β2-adrenoreceptor agonists. " }

Study 2

{ "type": "p", "children": [], "text": "\nStudy 2\n" }

Study 2 was a randomized, 3-cycle, 2-arm trial. Each cycle comprised of 28 days on treatment followed by 28 days off treatment. The first cycle was double-blind, placebo-controlled with eligible patients randomized 1:1 to TOBI Podhaler (4 times 28 mg capsules twice-daily) or placebo. Upon completion of the first cycle, patients who were randomized to the placebo treatment group received TOBI Podhaler for Cycles 2 and 3. The total treatment period was 24 weeks.

{ "type": "p", "children": [], "text": "Study 2 was a randomized, 3-cycle, 2-arm trial. Each cycle comprised of 28 days on treatment followed by 28 days off treatment. The first cycle was double-blind, placebo-controlled with eligible patients randomized 1:1 to TOBI Podhaler (4 times 28 mg capsules twice-daily) or placebo. Upon completion of the first cycle, patients who were randomized to the placebo treatment group received TOBI Podhaler for Cycles 2 and 3. The total treatment period was 24 weeks." }

A total of 95 patients were randomized into Study 2 and received TOBI Podhaler (n=46) or placebo (n=49) in Cycle 1. All patients were less than 22 years of age (mean age 13.3 years) and had not received inhaled antipseudomonal antibiotics within four months prior to screening; 56% were female and 84% were Caucasian. This study was stopped early for demonstrated benefit and the primary analysis used the set of patients included in the interim analysis (n=79); 16 patients did not have data on the primary endpoint at that time. Of the 79 patients included in the interim analysis, 18 patients were excluded due to a failure to meet spirometry quality review criteria as determined by an external review panel. This resulted in a total of 61 patients, 29 in the TOBI Podhaler arm and 32 in the placebo arm, who were included in the primary analysis.

{ "type": "p", "children": [], "text": "A total of 95 patients were randomized into Study 2 and received TOBI Podhaler (n=46) or placebo (n=49) in Cycle 1. All patients were less than 22 years of age (mean age 13.3 years) and had not received inhaled antipseudomonal antibiotics within four months prior to screening; 56% were female and 84% were Caucasian. This study was stopped early for demonstrated benefit and the primary analysis used the set of patients included in the interim analysis (n=79); 16 patients did not have data on the primary endpoint at that time. Of the 79 patients included in the interim analysis, 18 patients were excluded due to a failure to meet spirometry quality review criteria as determined by an external review panel. This resulted in a total of 61 patients, 29 in the TOBI Podhaler arm and 32 in the placebo arm, who were included in the primary analysis." }

In the primary analysis, TOBI Podhaler significantly improved lung function compared with placebo as measured by the relative change in FEV1 % predicted from baseline to the end of Cycle 1 dosing. This analysis adjusted for the covariates of baseline FEV1 % predicted, age, and region, and imputed for missing data. Treatment with TOBI Podhaler and placebo resulted in relative increases in FEV1 % predicted of 12.54% and 0.09%, respectively (LS mean difference = 12.44%; 95% CI: 4.89, 20.00; p=0.002). Analysis of absolute changes in FEV1 % predicted showed LS means of 6.38% for TOBI Podhaler and -0.52% for placebo with a difference of 6.90% (95% CI: 2.40, 11.40). Improvements in lung function were achieved during the subsequent cycles of treatment with TOBI Podhaler, although the magnitude was reduced (Figure 1).

{ "type": "p", "children": [], "text": "In the primary analysis, TOBI Podhaler significantly improved lung function compared with placebo as measured by the relative change in FEV1 % predicted from baseline to the end of Cycle 1 dosing. This analysis adjusted for the covariates of baseline FEV1 % predicted, age, and region, and imputed for missing data. Treatment with TOBI Podhaler and placebo resulted in relative increases in FEV1 % predicted of 12.54% and 0.09%, respectively (LS mean difference = 12.44%; 95% CI: 4.89, 20.00; p=0.002). Analysis of absolute changes in FEV1 % predicted showed LS means of 6.38% for TOBI Podhaler and -0.52% for placebo with a difference of 6.90% (95% CI: 2.40, 11.40). Improvements in lung function were achieved during the subsequent cycles of treatment with TOBI Podhaler, although the magnitude was reduced (Figure 1). " }

The percentage of patients using new antipseudomonal antibiotics in Cycle 1 was greater in the placebo treatment group (18.4%) compared with the TOBI Podhaler treatment group (13.1%). During the first cycle, 8.7% of TOBI Podhaler patients and 10.2% of placebo patients were treated with parenteral antipseudomonal antibiotics. In Cycle 1, two patients (4.4%) in the TOBI Podhaler treatment group required respiratory-related hospitalizations, compared with six patients (12.2%) in the placebo treatment group.

{ "type": "p", "children": [], "text": "The percentage of patients using new antipseudomonal antibiotics in Cycle 1 was greater in the placebo treatment group (18.4%) compared with the TOBI Podhaler treatment group (13.1%). During the first cycle, 8.7% of TOBI Podhaler patients and 10.2% of placebo patients were treated with parenteral antipseudomonal antibiotics. In Cycle 1, two patients (4.4%) in the TOBI Podhaler treatment group required respiratory-related hospitalizations, compared with six patients (12.2%) in the placebo treatment group." }

{ "type": "", "children": [], "text": "" }

Study 3

{ "type": "p", "children": [], "text": "\nStudy 3\n" }

Study 3 was a randomized, double-blind, placebo-controlled trial, similar in design to Study 2. Eligible patients were randomized 1:1 to receive TOBI Podhaler (4 times 28 mg capsules twice-daily) or placebo for one cycle (28 days on-treatment and 28 days off-treatment).

{ "type": "p", "children": [], "text": "Study 3 was a randomized, double-blind, placebo-controlled trial, similar in design to Study 2. Eligible patients were randomized 1:1 to receive TOBI Podhaler (4 times 28 mg capsules twice-daily) or placebo for one cycle (28 days on-treatment and 28 days off-treatment)." }

A total of 62 patients were randomized into Study 3 and allocated to TOBI Podhaler (n=32) or placebo (n=30). All patients were less than 22 years of age (mean age 12.9 years) and had not received inhaled antipseudomonal antibiotics within 4 months prior to screening; 64.5% were female and 98.4% were Caucasian.

{ "type": "p", "children": [], "text": "A total of 62 patients were randomized into Study 3 and allocated to TOBI Podhaler (n=32) or placebo (n=30). All patients were less than 22 years of age (mean age 12.9 years) and had not received inhaled antipseudomonal antibiotics within 4 months prior to screening; 64.5% were female and 98.4% were Caucasian." }

In this study, the results were not statistically significant for the primary lung function endpoint when adjusting for the covariates of age (<13 years, ≥13 years) and FEV1 % predicted at screening (<50%, ≥50%) and imputing for missing data. Improvement in lung function for TOBI Podhaler compared with placebo was evaluated using the relative change in FEV1 % predicted from baseline to the end of Cycle 1 dosing. Treatment with TOBI Podhaler (8.19%) compared to placebo (2.27%) failed to achieve statistical significance in relative change in FEV1 % predicted (LS mean difference = 5.91%; 95% CI: -2.54, 14.37; p=0.167). Analyses of absolute changes in FEV1 % predicted showed LS means of 4.86% for TOBI Podhaler and 0.48% for placebo with a difference of 4.38% (95% CI:-0.17, 8.94).

{ "type": "p", "children": [], "text": "In this study, the results were not statistically significant for the primary lung function endpoint when adjusting for the covariates of age (<13 years, ≥13 years) and FEV1 % predicted at screening (<50%, ≥50%) and imputing for missing data. Improvement in lung function for TOBI Podhaler compared with placebo was evaluated using the relative change in FEV1 % predicted from baseline to the end of Cycle 1 dosing. Treatment with TOBI Podhaler (8.19%) compared to placebo (2.27%) failed to achieve statistical significance in relative change in FEV1 % predicted (LS mean difference = 5.91%; 95% CI: -2.54, 14.37; p=0.167). Analyses of absolute changes in FEV1 % predicted showed LS means of 4.86% for TOBI Podhaler and 0.48% for placebo with a difference of 4.38% (95% CI:-0.17, 8.94). " }

Study 1

{ "type": "p", "children": [], "text": "\nStudy 1\n" }

Study 1 was a randomized, open-label, active-controlled parallel arm trial. Eligible patients were randomized 3:2 to TOBI Podhaler (4 times 28 mg capsules twice-daily) or TOBI (300 mg/5 mL twice-daily). Treatment was administered for 28 days, followed by 28 days off therapy (one cycle) for three cycles. The total treatment period was 24 weeks. The time to administer a dose of TOBI Podhaler (10th to 90th percentiles) ranged from 2 to 7 minutes at the end of the dosing period for Cycle 1, and 2 to 6 minutes at the end of the dosing period for Cycle 3.

{ "type": "p", "children": [], "text": "Study 1 was a randomized, open-label, active-controlled parallel arm trial. Eligible patients were randomized 3:2 to TOBI Podhaler (4 times 28 mg capsules twice-daily) or TOBI (300 mg/5 mL twice-daily). Treatment was administered for 28 days, followed by 28 days off therapy (one cycle) for three cycles. The total treatment period was 24 weeks. The time to administer a dose of TOBI Podhaler (10th to 90th percentiles) ranged from 2 to 7 minutes at the end of the dosing period for Cycle 1, and 2 to 6 minutes at the end of the dosing period for Cycle 3." }

A total of 517 patients were randomized in Study 1 and received TOBI Podhaler (n=308) or TOBI (n=209). Patients were predominantly 20 years of age or older (mean age 25.6 years) with no inhaled antipseudomonal antibiotic use within 28 days prior to study drug administration; 45% were female and 91% were Caucasian.

{ "type": "p", "children": [], "text": "A total of 517 patients were randomized in Study 1 and received TOBI Podhaler (n=308) or TOBI (n=209). Patients were predominantly 20 years of age or older (mean age 25.6 years) with no inhaled antipseudomonal antibiotic use within 28 days prior to study drug administration; 45% were female and 91% were Caucasian." }

The primary purpose of Study 1 was to evaluate safety. Interpretation of efficacy results in Study 1 is limited by several factors including open-label design, testing of multiple secondary endpoints, and missing values for the outcome of FEV1 % predicted. The number (%) of patients with missing values for FEV1 % predicted at Weeks 5 and 25 in the TOBI Podhaler treated group were 40 (13.0%) and 86 (27.9%) compared to 15 (7.2%) and 40 (19.1%) in the TOBI treated group. Using imputation of the missing data, the mean differences (TOBI Podhaler minus TOBI) in the percent relative change from baseline in FEV1 % predicted at Weeks 5 and 25 were -0.87 (95% CI: -3.80, 2.07) and 1.62 (95% CI: -0.90, 4.14), respectively.

{ "type": "p", "children": [], "text": "The primary purpose of Study 1 was to evaluate safety. Interpretation of efficacy results in Study 1 is limited by several factors including open-label design, testing of multiple secondary endpoints, and missing values for the outcome of FEV1 % predicted. The number (%) of patients with missing values for FEV1 % predicted at Weeks 5 and 25 in the TOBI Podhaler treated group were 40 (13.0%) and 86 (27.9%) compared to 15 (7.2%) and 40 (19.1%) in the TOBI treated group. Using imputation of the missing data, the mean differences (TOBI Podhaler minus TOBI) in the percent relative change from baseline in FEV1 % predicted at Weeks 5 and 25 were -0.87 (95% CI: -3.80, 2.07) and 1.62 (95% CI: -0.90, 4.14), respectively. " }

{ "type": "", "children": [], "text": "" }

TOBI Podhaler contains aluminum blister-packaged 28 mg TOBI Podhaler (tobramycin inhalation powder) clear, colorless hypromellose capsules with “MYL TPH” in blue radial imprint on one part of the capsule and the Mylan logo in blue radial imprint on the other part of the capsule, and Podhaler devices.

Each Podhaler device consists of the inhaler body, mouthpiece, capsule chamber and blue push button. The Podhaler device is provided in a case that protects the device during shipment, storage and its one week in-use period.

Unit dose (blister pack), Box of 224 capsules contains:      NDC 49502-401-24

Unit dose (blister pack), Box of 56 capsules (7-day pack) contains:     NDC 49502-401-56

56 capsules (7 blister cards of 8 capsules)

1 Podhaler device

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)

Protect TOBI Podhaler from moisture.

Keep this and all drugs out of the reach of children.

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

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

Important Administration Information

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

Information on the long-term efficacy and safety of TOBI Podhaler is limited. There is no information in patients with limited pulmonary reserve (FEV1 <25% predicted). Decreased susceptibility of Pseudomonas aeruginosa to tobramycin has been seen with use of TOBI Podhaler. The relationship between in vitro susceptibility test results and clinical outcome with TOBI Podhaler therapy is not clear. Occurrence of decreased susceptibility on treatment should be monitored, and treatment with an alternative therapy should be considered if clinical worsening is observed.

{ "type": "p", "children": [], "text": "Information on the long-term efficacy and safety of TOBI Podhaler is limited. There is no information in patients with limited pulmonary reserve (FEV1 <25% predicted). Decreased susceptibility of Pseudomonas aeruginosa to tobramycin has been seen with use of TOBI Podhaler. The relationship between in vitro susceptibility test results and clinical outcome with TOBI Podhaler therapy is not clear. Occurrence of decreased susceptibility on treatment should be monitored, and treatment with an alternative therapy should be considered if clinical worsening is observed." }

TOBI Podhaler may not be tolerated by all patients. Patients should be instructed to consider alternative therapy if they are unable to tolerate TOBI Podhaler. Patients should be advised to complete a full 28-day course of TOBI Podhaler, even if they are feeling better. After 28 days of therapy, patients should stop TOBI Podhaler therapy for the next 28 days, and then resume therapy for the next 28-day on and 28-day off cycle.

{ "type": "p", "children": [], "text": "TOBI Podhaler may not be tolerated by all patients. Patients should be instructed to consider alternative therapy if they are unable to tolerate TOBI Podhaler. Patients should be advised to complete a full 28-day course of TOBI Podhaler, even if they are feeling better. After 28 days of therapy, patients should stop TOBI Podhaler therapy for the next 28 days, and then resume therapy for the next 28-day on and 28-day off cycle." }

Patients should be advised that if they have been prescribed a 7-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then they must count each day of use toward the 28 day on-treatment part of their cycle. Patients should only take a total of 28 consecutive days of treatment during a cycle.

{ "type": "p", "children": [], "text": "Patients should be advised that if they have been prescribed a 7-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then they must count each day of use toward the 28 day on-treatment part of their cycle. Patients should only take a total of 28 consecutive days of treatment during a cycle." }

Similarly, patients should be advised that if they have been prescribed a 1-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then they must count each day of use toward the 28 day on-treatment part of their cycle. Patients should only take a total of 28 consecutive days of treatment during a cycle.

{ "type": "p", "children": [], "text": "Similarly, patients should be advised that if they have been prescribed a 1-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then they must count each day of use toward the 28 day on-treatment part of their cycle. Patients should only take a total of 28 consecutive days of treatment during a cycle." }

It is important for patients to understand how to correctly administer TOBI Podhaler capsules using the Podhaler device. It is recommended that caregivers and patients be adequately trained in the proper use of the TOBI Podhaler prior to use. [See Instructions for Use at the end of the Patient Information leaflet.] Caregivers should provide assistance to children using TOBI Podhaler (including preparing the dose for inhalation) particularly for those aged 10 years or younger, and should continue to supervise them until they are able to use the Podhaler device properly without help.

{ "type": "p", "children": [], "text": "It is important for patients to understand how to correctly administer TOBI Podhaler capsules using the Podhaler device. It is recommended that caregivers and patients be adequately trained in the proper use of the TOBI Podhaler prior to use. [See Instructions for Use at the end of the Patient Information leaflet.] Caregivers should provide assistance to children using TOBI Podhaler (including preparing the dose for inhalation) particularly for those aged 10 years or younger, and should continue to supervise them until they are able to use the Podhaler device properly without help." }

For patients taking several different inhaled medications and/or performing chest physiotherapy, advise the patient regarding the order in which they should take the therapies. It is recommended that TOBI Podhaler be taken last.

{ "type": "p", "children": [], "text": "For patients taking several different inhaled medications and/or performing chest physiotherapy, advise the patient regarding the order in which they should take the therapies. It is recommended that TOBI Podhaler be taken last." }

Difficulty Breathing:

{ "type": "p", "children": [], "text": "\nDifficulty Breathing:" }

Advise patients to inform their physicians if they experience shortness of breath or wheezing after administration of Tobi Podhaler. Tobi Podhaler can cause a narrowing of the airway [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise patients to inform their physicians if they experience shortness of breath or wheezing after administration of Tobi Podhaler. Tobi Podhaler can cause a narrowing of the airway [see Warnings and Precautions (5.1)].\n" }

Hearing Loss:

{ "type": "p", "children": [], "text": "\nHearing Loss: " }

Advise patients to inform their physician if they experience ringing in the ears, dizziness, or any changes in hearing because Tobi Podhaler has been associated with hearing loss [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Advise patients to inform their physician if they experience ringing in the ears, dizziness, or any changes in hearing because Tobi Podhaler has been associated with hearing loss [see Warnings and Precautions (5.2)].\n" }

Kidney Damage:

{ "type": "p", "children": [], "text": "\nKidney Damage: " }

Advise patients to inform their physician if they have any history of kidney problems because Tobi Podhaler is in a class of drugs that have caused kidney damage [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "Advise patients to inform their physician if they have any history of kidney problems because Tobi Podhaler is in a class of drugs that have caused kidney damage [see Warnings and Precautions (5.3)]. " }

Embryo-Fetal Toxicity:

{ "type": "p", "children": [], "text": "\nEmbryo-Fetal Toxicity:\n" }

Advise pregnant women that aminoglycosides can cause irreversible congenital deafness when administered to a pregnant woman [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "Advise pregnant women that aminoglycosides can cause irreversible congenital deafness when administered to a pregnant woman [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1)].\n" }

Lactation:

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

Advise a woman to monitor their breastfed infants for diarrhea and/or bloody stools [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "Advise a woman to monitor their breastfed infants for diarrhea and/or bloody stools [see Use in Specific Populations (8.2)]." }

Cough:

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

Inform patients that cough was reported with the use of TOBI Podhaler in clinical trials. If coughing that may be experienced with TOBI Podhaler becomes bothersome or cannot be tolerated, advise patients that tobramycin inhalation solution or alternative therapeutic options may be considered.

{ "type": "p", "children": [], "text": "Inform patients that cough was reported with the use of TOBI Podhaler in clinical trials. If coughing that may be experienced with TOBI Podhaler becomes bothersome or cannot be tolerated, advise patients that tobramycin inhalation solution or alternative therapeutic options may be considered." }

<div class="scrollingtable"><table width="100%"> <col width="33%"/> <col width="33%"/> <col width="33%"/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First"> <span class="Bold">TOBI (TOH-bee) Podhaler (POD-hay-ler)</span> </p> <p>(tobramycin inhalation powder)</p> <p>for oral inhalation use</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Important information: Do not swallow TOBI Podhaler capsules. TOBI Podhaler capsules are used only with the Podhaler device and inhaled through your mouth (oral inhalation). Never place a capsule in the mouthpiece of the Podhaler device.</span> </p> <p>Read this Patient Information leaflet before you start using TOBI Podhaler 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.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What is TOBI Podhaler?</span> </p> <p>TOBI Podhaler is a prescription medicine used to treat people with cystic fibrosis who have a bacterial infection called <span class="Italics">Pseudomonas aeruginosa</span>. TOBI Podhaler contains an antibacterial medicine called tobramycin (an aminoglycoside).</p> <p>It is not known if TOBI Podhaler is safe and effective:</p> <dl> <dt>•</dt> <dd>in children under 6 years of age</dd> <dt>•</dt> <dd>in people who have an FEV<span class="Sub">1</span> less than 25% or greater than 80% predicted</dd> <dt>•</dt> <dd>in people who are colonized with a bacterium called <span class="Italics">Burkholderia cepacia</span> </dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Who should not use TOBI Podhaler?</span> </p> <p>Do not use TOBI Podhaler if you are allergic to tobramycin, any of the ingredients in TOBI Podhaler, or to any other aminoglycoside antibacterial medicines.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What should I tell my healthcare provider before using TOBI Podhaler?</span> </p> <p> <span class="Bold">Before using TOBI Podhaler, tell your healthcare provider about all of your medical conditions, including if you:</span> </p> <dl> <dt>•</dt> <dd>have or have had hearing problems (including noises in your ears such as ringing or hissing), hearing loss, or your mother has had hearing problems after taking an aminoglycoside.</dd> <dt>•</dt> <dd>have been told you have certain gene variants (a change in the gene) related to hearing abnormalities inherited from your mother.</dd> <dt>•</dt> <dd>have dizziness.</dd> <dt>•</dt> <dd>have or have had kidney problems.</dd> <dt>•</dt> <dd>have or have had problems with muscle weakness such as myasthenia gravis or Parkinson’s disease.</dd> <dt>•</dt> <dd>have or have had breathing problems such as wheezing, coughing, or chest tightness.</dd> <dt>•</dt> <dd>have had an organ transplant.</dd> <dt>•</dt> <dd>are pregnant or plan to become pregnant. TOBI Podhaler contains a medicine that can harm your unborn baby. See “<span class="Bold">What are the possible side effects of TOBI Podhaler?</span>” for more information. </dd> <dt>•</dt> <dd>are breastfeeding or plan to breastfeed. It is not known if the medicine in TOBI Podhaler (tobramycin inhalation powder) passes into your breast milk. </dd> </dl> <p> <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.</p> <p>Using TOBI Podhaler with certain other medicines can cause serious side effects. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.</p> <p>If you are using TOBI Podhaler, you should discuss with your healthcare provider if you should take:</p> <dl> <dt>•</dt> <dd>other medicines that may harm your nervous system, kidneys, or hearing</dd> <dt>•</dt> <dd>“water pills” (diuretics) such as Edecrin (ethacrynic acid), Lasix (furosemide), or intravenous mannitol </dd> <dt>•</dt> <dd>urea</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How should I use TOBI Podhaler?</span> </p> <dl> <dt>•</dt> <dd>See the step-by-step Instructions for Use at the end of this Patient Information leaflet about the right way to use TOBI Podhaler. Do not use TOBI Podhaler unless your healthcare provider has taught you how to use it the right way. </dd> <dt>•</dt> <dd>Use TOBI Podhaler exactly as your healthcare provider tells you to use it. Ask your healthcare provider or pharmacist if you are not sure.</dd> <dt>•</dt> <dd>The usual dose for adults and children over 6 years of age is: <dl> <dt>•</dt> <dd>The contents of 4 TOBI Podhaler capsules inhaled by mouth in the morning using your Podhaler device and the contents of 4 TOBI Podhaler capsules inhaled by mouth in the evening using your Podhaler device.</dd> <dt>•</dt> <dd>Check to see that each capsule is empty after inhaling. If powder remains in the capsule, repeat inhalation until the capsule is empty.</dd> </dl> </dd> <dt>•</dt> <dd>Each dose of 4 TOBI Podhaler capsules should be taken as close to 12 hours apart as possible.</dd> <dt>•</dt> <dd>You should not take your dose of 4 TOBI Podhaler capsules less than 6 hours apart.</dd> <dt>•</dt> <dd>After using TOBI Podhaler for 28 days, you should stop using it and wait 28 days. After you have stopped using TOBI Podhaler for 28 days, you should start using TOBI Podhaler again for 28 days. Complete the full 28-day course even if you are feeling better. It is important that you keep to the 28-day on, 28-day off cycle (See Figure A).</dd> </dl> </td> </tr> <tr> <td align="center" class="Lrule Rrule" colspan="3" valign="top"><a name="id573011681"></a><img alt="Patient Information Leaflet Figure A" src="/dailymed/image.cfm?name=image-01.jpg&amp;setid=c4b5bb1f-e158-4ac1-9c35-e98a416c743a"/><p class="MultiMediaCaptionNotCentered">(Figure A) </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <dl> <dt>•</dt> <dd>If you have been prescribed a 7-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then you must count each day of use toward the 28-day on-treatment part of the cycle. You should only take a total of 28 consecutive days of treatment during a cycle. </dd> <dt>•</dt> <dd>If you have been prescribed a 1-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then you must count each day of use toward the 28-day on-treatment part of the cycle. You should only take a total of 28 consecutive days of treatment during a cycle.</dd> <dt>•</dt> <dd>If you are taking other medicines inhaled through your mouth, your healthcare provider will tell you how to take your medicines the right way.</dd> <dt>•</dt> <dd>If you are doing therapies for cystic fibrosis (chest physiotherapy), you should use TOBI Podhaler after your other therapies are done.</dd> <dt>•</dt> <dd>If you inhale too much TOBI Podhaler, tell your healthcare provider right away.</dd> <dt>•</dt> <dd>If you accidentally swallow TOBI Podhaler capsules, tell your healthcare provider right away.</dd> <dt>•</dt> <dd>Use a new TOBI Podhaler device every 7 days. </dd> <dt>•</dt> <dd>Caregivers should help children who are 10 years of age and younger use TOBI Podhaler, and keep watching them use their TOBI Podhaler until they are able to use it the right way without help.</dd> <dt>•</dt> <dd>Tell your doctor if your symptoms worsen while using your TOBI Podhaler.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the possible side effects of TOBI Podhaler?</span> </p> <p> <span class="Bold">TOBI Podhaler can cause serious side effects, including:</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">severe breathing problems (bronchospasm)</span>. Tell your healthcare provider right away if you get any of these symptoms of bronchospasm while using TOBI Podhaler:<dl> <dt>•</dt> <dd>shortness of breath with wheezing</dd> <dt>•</dt> <dd>coughing and chest tightness</dd> </dl> </dd> <dt>•</dt> <dd> <span class="Bold">hearing loss or ringing in the ears (ototoxicity)</span>. Tell your healthcare provider right away if you have hearing loss or hear noises in your ears such as ringing or hissing, or if you develop vertigo, difficulty with balance or dizziness.</dd> <dt>•</dt> <dd> <span class="Bold">worsening kidney problems (nephrotoxicity)</span>. TOBI Podhaler is in a class of medicines which may cause worsening kidney problems, especially in people with known or suspected kidney problems. Your healthcare provider may do a blood test to check how your kidneys are working while you are using TOBI Podhaler.</dd> <dt>•</dt> <dd> <span class="Bold">worsening muscle weakness</span>. TOBI Podhaler is in a class of medicines which can cause muscle weakness to get worse in people who already have problems with muscle weakness (myasthenia gravis or Parkinson’s disease).</dd> <dt>•</dt> <dd> <span class="Bold">The medicine in TOBI Podhaler is in a class of medicines which may cause harm to an unborn baby</span>.</dd> </dl> <p> <span class="Bold">The most common side effects of TOBI Podhaler include:</span> </p> </td> </tr> <tr> <td class="Lrule" valign="top"> <dl> <dt>•</dt> <dd>cough</dd> <dt>•</dt> <dd>worsening of lung problems or cystic fibrosis</dd> <dt>•</dt> <dd>productive cough</dd> </dl> </td><td valign="top"> <dl> <dt>•</dt> <dd>shortness of breath</dd> <dt>•</dt> <dd>fever</dd> <dt>•</dt> <dd>sore throat</dd> <dt>•</dt> <dd>changes in your voice (hoarseness)</dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt>•</dt> <dd>coughing up blood</dd> <dt>•</dt> <dd>headache</dd> </dl> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First">Let your healthcare provider know if your symptoms get worse. Some patients may not be able to continue using TOBI Podhaler and need to consider other treatments. Tell your healthcare provider about any side effect that bothers you enough to stop treatment or that does not go away.</p> <p>These are not all of the possible side effects of TOBI Podhaler. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">General information about the safe and effective use of TOBI Podhaler.</span> </p> <p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TOBI Podhaler for a condition for which it was not prescribed. Do not give TOBI Podhaler to other people, even if they have the same problem you have. It may harm them.</p> <p>You can ask your healthcare provider or pharmacist for information about TOBI Podhaler that was written for healthcare professionals.</p> <p>For more information, go to www.TOBIPodhaler.com or call 1-877-999-TOBI (8624).</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">What are the ingredients in TOBI Podhaler?</span> </p> <p> <span class="Bold">Active ingredient</span>: tobramycin</p> <p> <span class="Bold">Inactive ingredients</span>: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment)</p> </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col width=\"33%\"/>\n<col width=\"33%\"/>\n<col width=\"33%\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Botrule Lrule Rrule Toprule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">TOBI (TOH-bee) Podhaler (POD-hay-ler)</span>\n</p>\n<p>(tobramycin inhalation powder)</p>\n<p>for oral inhalation use</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Important information: Do not swallow TOBI Podhaler capsules. TOBI Podhaler capsules are used only with the Podhaler device and inhaled through your mouth (oral inhalation). Never place a capsule in the mouthpiece of the Podhaler device.</span>\n</p>\n<p>Read this Patient Information leaflet before you start using TOBI Podhaler 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.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What is TOBI Podhaler?</span>\n</p>\n<p>TOBI Podhaler is a prescription medicine used to treat people with cystic fibrosis who have a bacterial infection called <span class=\"Italics\">Pseudomonas aeruginosa</span>. TOBI Podhaler contains an antibacterial medicine called tobramycin (an aminoglycoside).</p>\n<p>It is not known if TOBI Podhaler is safe and effective:</p>\n<dl>\n<dt>•</dt>\n<dd>in children under 6 years of age</dd>\n<dt>•</dt>\n<dd>in people who have an FEV<span class=\"Sub\">1</span> less than 25% or greater than 80% predicted</dd>\n<dt>•</dt>\n<dd>in people who are colonized with a bacterium called <span class=\"Italics\">Burkholderia cepacia</span>\n</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Who should not use TOBI Podhaler?</span>\n</p>\n<p>Do not use TOBI Podhaler if you are allergic to tobramycin, any of the ingredients in TOBI Podhaler, or to any other aminoglycoside antibacterial medicines.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What should I tell my healthcare provider before using TOBI Podhaler?</span>\n</p>\n<p>\n<span class=\"Bold\">Before using TOBI Podhaler, tell your healthcare provider about all of your medical conditions, including if you:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>have or have had hearing problems (including noises in your ears such as ringing or hissing), hearing loss, or your mother has had hearing problems after taking an aminoglycoside.</dd>\n<dt>•</dt>\n<dd>have been told you have certain gene variants (a change in the gene) related to hearing abnormalities inherited from your mother.</dd>\n<dt>•</dt>\n<dd>have dizziness.</dd>\n<dt>•</dt>\n<dd>have or have had kidney problems.</dd>\n<dt>•</dt>\n<dd>have or have had problems with muscle weakness such as myasthenia gravis or Parkinson’s disease.</dd>\n<dt>•</dt>\n<dd>have or have had breathing problems such as wheezing, coughing, or chest tightness.</dd>\n<dt>•</dt>\n<dd>have had an organ transplant.</dd>\n<dt>•</dt>\n<dd>are pregnant or plan to become pregnant. TOBI Podhaler contains a medicine that can harm your unborn baby. See “<span class=\"Bold\">What are the possible side effects of TOBI Podhaler?</span>” for more information. </dd>\n<dt>•</dt>\n<dd>are breastfeeding or plan to breastfeed. It is not known if the medicine in TOBI Podhaler (tobramycin inhalation powder) passes into your breast milk. </dd>\n</dl>\n<p>\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.</p>\n<p>Using TOBI Podhaler with certain other medicines can cause serious side effects. Ask your healthcare provider or pharmacist for a list of these medicines, if you are not sure. Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.</p>\n<p>If you are using TOBI Podhaler, you should discuss with your healthcare provider if you should take:</p>\n<dl>\n<dt>•</dt>\n<dd>other medicines that may harm your nervous system, kidneys, or hearing</dd>\n<dt>•</dt>\n<dd>“water pills” (diuretics) such as Edecrin (ethacrynic acid), Lasix (furosemide), or intravenous mannitol </dd>\n<dt>•</dt>\n<dd>urea</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">How should I use TOBI Podhaler?</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>See the step-by-step Instructions for Use at the end of this Patient Information leaflet about the right way to use TOBI Podhaler. Do not use TOBI Podhaler unless your healthcare provider has taught you how to use it the right way. </dd>\n<dt>•</dt>\n<dd>Use TOBI Podhaler exactly as your healthcare provider tells you to use it. Ask your healthcare provider or pharmacist if you are not sure.</dd>\n<dt>•</dt>\n<dd>The usual dose for adults and children over 6 years of age is: <dl>\n<dt>•</dt>\n<dd>The contents of 4 TOBI Podhaler capsules inhaled by mouth in the morning using your Podhaler device and the contents of 4 TOBI Podhaler capsules inhaled by mouth in the evening using your Podhaler device.</dd>\n<dt>•</dt>\n<dd>Check to see that each capsule is empty after inhaling. If powder remains in the capsule, repeat inhalation until the capsule is empty.</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>Each dose of 4 TOBI Podhaler capsules should be taken as close to 12 hours apart as possible.</dd>\n<dt>•</dt>\n<dd>You should not take your dose of 4 TOBI Podhaler capsules less than 6 hours apart.</dd>\n<dt>•</dt>\n<dd>After using TOBI Podhaler for 28 days, you should stop using it and wait 28 days. After you have stopped using TOBI Podhaler for 28 days, you should start using TOBI Podhaler again for 28 days. Complete the full 28-day course even if you are feeling better. It is important that you keep to the 28-day on, 28-day off cycle (See Figure A).</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\"><a name=\"id573011681\"></a><img alt=\"Patient Information Leaflet Figure A\" src=\"/dailymed/image.cfm?name=image-01.jpg&amp;setid=c4b5bb1f-e158-4ac1-9c35-e98a416c743a\"/><p class=\"MultiMediaCaptionNotCentered\">(Figure A) </p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>If you have been prescribed a 7-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then you must count each day of use toward the 28-day on-treatment part of the cycle. You should only take a total of 28 consecutive days of treatment during a cycle. </dd>\n<dt>•</dt>\n<dd>If you have been prescribed a 1-day pack of TOBI Podhaler either immediately before or during a 28-day treatment with TOBI Podhaler, then you must count each day of use toward the 28-day on-treatment part of the cycle. You should only take a total of 28 consecutive days of treatment during a cycle.</dd>\n<dt>•</dt>\n<dd>If you are taking other medicines inhaled through your mouth, your healthcare provider will tell you how to take your medicines the right way.</dd>\n<dt>•</dt>\n<dd>If you are doing therapies for cystic fibrosis (chest physiotherapy), you should use TOBI Podhaler after your other therapies are done.</dd>\n<dt>•</dt>\n<dd>If you inhale too much TOBI Podhaler, tell your healthcare provider right away.</dd>\n<dt>•</dt>\n<dd>If you accidentally swallow TOBI Podhaler capsules, tell your healthcare provider right away.</dd>\n<dt>•</dt>\n<dd>Use a new TOBI Podhaler device every 7 days. </dd>\n<dt>•</dt>\n<dd>Caregivers should help children who are 10 years of age and younger use TOBI Podhaler, and keep watching them use their TOBI Podhaler until they are able to use it the right way without help.</dd>\n<dt>•</dt>\n<dd>Tell your doctor if your symptoms worsen while using your TOBI Podhaler.</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the possible side effects of TOBI Podhaler?</span>\n</p>\n<p>\n<span class=\"Bold\">TOBI Podhaler can cause serious side effects, including:</span>\n</p>\n<dl>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">severe breathing problems (bronchospasm)</span>. Tell your healthcare provider right away if you get any of these symptoms of bronchospasm while using TOBI Podhaler:<dl>\n<dt>•</dt>\n<dd>shortness of breath with wheezing</dd>\n<dt>•</dt>\n<dd>coughing and chest tightness</dd>\n</dl>\n</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">hearing loss or ringing in the ears (ototoxicity)</span>. Tell your healthcare provider right away if you have hearing loss or hear noises in your ears such as ringing or hissing, or if you develop vertigo, difficulty with balance or dizziness.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">worsening kidney problems (nephrotoxicity)</span>. TOBI Podhaler is in a class of medicines which may cause worsening kidney problems, especially in people with known or suspected kidney problems. Your healthcare provider may do a blood test to check how your kidneys are working while you are using TOBI Podhaler.</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">worsening muscle weakness</span>. TOBI Podhaler is in a class of medicines which can cause muscle weakness to get worse in people who already have problems with muscle weakness (myasthenia gravis or Parkinson’s disease).</dd>\n<dt>•</dt>\n<dd>\n<span class=\"Bold\">The medicine in TOBI Podhaler is in a class of medicines which may cause harm to an unborn baby</span>.</dd>\n</dl>\n<p>\n<span class=\"Bold\">The most common side effects of TOBI Podhaler include:</span>\n</p>\n</td>\n</tr>\n<tr>\n<td class=\"Lrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>cough</dd>\n<dt>•</dt>\n<dd>worsening of lung problems or cystic fibrosis</dd>\n<dt>•</dt>\n<dd>productive cough</dd>\n</dl>\n</td><td valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>shortness of breath</dd>\n<dt>•</dt>\n<dd>fever</dd>\n<dt>•</dt>\n<dd>sore throat</dd>\n<dt>•</dt>\n<dd>changes in your voice (hoarseness)</dd>\n</dl>\n</td><td class=\"Rrule\" valign=\"top\">\n<dl>\n<dt>•</dt>\n<dd>coughing up blood</dd>\n<dt>•</dt>\n<dd>headache</dd>\n</dl>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">Let your healthcare provider know if your symptoms get worse. Some patients may not be able to continue using TOBI Podhaler and need to consider other treatments. Tell your healthcare provider about any side effect that bothers you enough to stop treatment or that does not go away.</p>\n<p>These are not all of the possible side effects of TOBI Podhaler. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</p>\n</td>\n</tr>\n<tr>\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">General information about the safe and effective use of TOBI Podhaler.</span>\n</p>\n<p>Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use TOBI Podhaler for a condition for which it was not prescribed. Do not give TOBI Podhaler to other people, even if they have the same problem you have. It may harm them.</p>\n<p>You can ask your healthcare provider or pharmacist for information about TOBI Podhaler that was written for healthcare professionals.</p>\n<p>For more information, go to www.TOBIPodhaler.com or call 1-877-999-TOBI (8624).</p>\n</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Botrule Lrule Rrule\" colspan=\"3\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">What are the ingredients in TOBI Podhaler?</span>\n</p>\n<p>\n<span class=\"Bold\">Active ingredient</span>: tobramycin</p>\n<p>\n<span class=\"Bold\">Inactive ingredients</span>: 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment)</p>\n</td>\n</tr>\n</tbody>\n</table></div>" }

TOBI (TOH-bee) Podhaler (POD-hay-ler)

{ "type": "p", "children": [], "text": "\nTOBI (TOH-bee) Podhaler (POD-hay-ler)\n" }

(tobramycin inhalation powder)

{ "type": "p", "children": [], "text": "(tobramycin inhalation powder)" }

Important Information:

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

{ "type": "", "children": [], "text": "" }

Note:

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

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Getting ready:

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

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Preparing your TOBI Podhaler dose

{ "type": "p", "children": [], "text": "\nPreparing your TOBI Podhaler dose\n" }

Your Podhaler device comes in a storage case with a lid. The device has a removable mouthpiece, capsule chamber and a button at its base (See Figure C).

{ "type": "p", "children": [], "text": "Your Podhaler device comes in a storage case with a lid. The device has a removable mouthpiece, capsule chamber and a button at its base (See Figure C)." }

Step 1: Just before use, hold the base of the storage case and unscrew the lid by turning it to the left (counter-clockwise) (See Figure D). Set the lid aside.

{ "type": "p", "children": [], "text": "\nStep 1: Just before use, hold the base of the storage case and unscrew the lid by turning it to the left (counter-clockwise) (See Figure D). Set the lid aside." }

Step 2: Leave the Podhaler device in the base of the storage case while you prepare your dose (See Figure E).

{ "type": "p", "children": [], "text": "\nStep 2: Leave the Podhaler device in the base of the storage case while you prepare your dose (See Figure E)." }

Step 3: Hold the body of the Podhaler device and unscrew the mouthpiece by turning it to the left (counter-clockwise direction) (See Figure F). Set the mouthpiece aside on a clean, dry surface.

{ "type": "p", "children": [], "text": "\nStep 3: Hold the body of the Podhaler device and unscrew the mouthpiece by turning it to the left (counter-clockwise direction) (See Figure F). Set the mouthpiece aside on a clean, dry surface." }

Note: Each blister card contains 8 TOBI Podhaler capsules: 4 capsules for inhalation in the morning and 4 capsules for inhalation in the evening.

{ "type": "p", "children": [], "text": "\nNote: Each blister card contains 8 TOBI Podhaler capsules: 4 capsules for inhalation in the morning and 4 capsules for inhalation in the evening. \n" }

Step 4: Take 1 blister card and tear the pre-cut lines along the length (See Figure G) then tear at the pre-cut lines along the width (See Figure H).

{ "type": "p", "children": [], "text": "\nStep 4: Take 1 blister card and tear the pre-cut lines along the length (See Figure G) then tear at the pre-cut lines along the width (See Figure H)." }

Step 5: Peel (by rolling back) the foil that covers 1 TOBI Podhaler capsule on the blister card (See Figure I). Always hold the foil close to where you are peeling.

{ "type": "p", "children": [], "text": "\nStep 5: Peel (by rolling back) the foil that covers 1 TOBI Podhaler capsule on the blister card (See Figure I). Always hold the foil close to where you are peeling." }

Step 6: Take out 1 TOBI Podhaler capsule from the blister card (See Figure J). Note: Only peel back the foil from 1 capsule at a time and remove the capsule just before you are going to use it in the device because the blister protects the capsule from moisture.

{ "type": "p", "children": [], "text": "\nStep 6: Take out 1 TOBI Podhaler capsule from the blister card (See Figure J). Note: Only peel back the foil from 1 capsule at a time and remove the capsule just before you are going to use it in the device because the blister protects the capsule from moisture." }

Step 7: Place the TOBI Podhaler capsule in the capsule chamber at the top of the Podhaler device right away (See Figure K). Do not put the capsule directly into the top of the mouthpiece.

{ "type": "p", "children": [], "text": "\nStep 7: Place the TOBI Podhaler capsule in the capsule chamber at the top of the Podhaler device right away (See Figure K). Do not put the capsule directly into the top of the mouthpiece." }

Step 8: Put the mouthpiece back on your Podhaler device and screw the mouthpiece on by turning it to the right (clockwise) until it is tight (See Figure L). Do not overtighten.

{ "type": "p", "children": [], "text": "\nStep 8: Put the mouthpiece back on your Podhaler device and screw the mouthpiece on by turning it to the right (clockwise) until it is tight (See Figure L). Do not overtighten." }

Step 9: Remove the Podhaler device from the base of the case. Hold the Podhaler device with the mouthpiece pointing down. Put your thumb on the blue button and press the blue button all the way down (See Figure M). Let go of the blue button. Do not press the blue button more than 1 time. The chances of the capsule breaking into pieces will be increased if the capsule is accidentally pierced (a hole put in it) more than 1 time.

{ "type": "p", "children": [], "text": "\nStep 9: Remove the Podhaler device from the base of the case. Hold the Podhaler device with the mouthpiece pointing down. Put your thumb on the blue button and press the blue button all the way down (See Figure M). Let go of the blue button. Do not press the blue button more than 1 time. The chances of the capsule breaking into pieces will be increased if the capsule is accidentally pierced (a hole put in it) more than 1 time." }

Taking your TOBI Podhaler dose

{ "type": "p", "children": [], "text": "\nTaking your TOBI Podhaler dose \n" }

Note: You will need to repeat Step 10 to Step 14 for each capsule so you inhale each capsule 2 times to empty the capsule.

{ "type": "p", "children": [], "text": "\nNote: You will need to repeat Step 10 to Step 14 for each capsule so you inhale each capsule 2 times to empty the capsule.\n" }

Step 10: Breathe out (exhale) all the way (See Figure N). Do not blow or exhale into the mouthpiece.

{ "type": "p", "children": [], "text": "\nStep 10: Breathe out (exhale) all the way (See Figure N). Do not blow or exhale into the mouthpiece." }

Step 11: Place your mouth over the mouthpiece and close your lips tightly around it (See Figure O).

{ "type": "p", "children": [], "text": "\nStep 11: Place your mouth over the mouthpiece and close your lips tightly around it (See Figure O)." }

Step 12: Inhale deeply with a single breath (See Figure P).

{ "type": "p", "children": [], "text": "\nStep 12: Inhale deeply with a single breath (See Figure P)." }

Step 13: Remove the Podhaler device from your mouth and hold your breath for about 5 seconds.

{ "type": "p", "children": [], "text": "\nStep 13: Remove the Podhaler device from your mouth and hold your breath for about 5 seconds." }

Step 14: Exhale and take a few normal breaths away from the Podhaler device. Do not blow or exhale into the mouthpiece.

{ "type": "p", "children": [], "text": "\nStep 14: Exhale and take a few normal breaths away from the Podhaler device. Do not blow or exhale into the mouthpiece." }

Step 15: Repeat Step 10 through Step 14 using the same capsule.

{ "type": "p", "children": [], "text": "\nStep 15: Repeat Step 10 through Step 14 using the same capsule." }

{ "type": "", "children": [], "text": "" }

Step 16: Unscrew the mouthpiece by turning it to the left (counterclockwise) and remove the TOBI Podhaler capsule from the capsule chamber (See Figure Q and Figure R below).

{ "type": "p", "children": [], "text": "\nStep 16: Unscrew the mouthpiece by turning it to the left (counterclockwise) and remove the TOBI Podhaler capsule from the capsule chamber (See Figure Q and Figure R below)." }

Step 17: Hold the used capsule up to the light and look through it. It should be empty with only a fine coating of powder remaining on the inside surface of the capsule (See Figure S). If the capsule is empty, throw it away and go to Step 18.

{ "type": "p", "children": [], "text": "\nStep 17: Hold the used capsule up to the light and look through it. It should be empty with only a fine coating of powder remaining on the inside surface of the capsule (See Figure S). If the capsule is empty, throw it away and go to Step 18." }

{ "type": "", "children": [], "text": "" }

What to do with a capsule that has not been emptied:

{ "type": "p", "children": [], "text": "\nWhat to do with a capsule that has not been emptied:\n" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

{ "type": "", "children": [], "text": "" }

Step 18: Repeat Step 5 to Step 17 for 3 more times until your full dose (4 capsules) has been taken (See Figure V).

{ "type": "p", "children": [], "text": "\nStep 18: Repeat Step 5 to Step 17 for 3 more times until your full dose (4 capsules) has been taken (See Figure V)." }

After your TOBI Podhaler dose:

{ "type": "p", "children": [], "text": "\nAfter your TOBI Podhaler dose:\n" }

Step 19: Do not store the TOBI Podhaler capsules in the Podhaler device.

{ "type": "p", "children": [], "text": "\nStep 19: Do not store the TOBI Podhaler capsules in the Podhaler device." }

Step 20: Put the mouthpiece back on to your Podhaler device and screw the mouthpiece on by turning it to the right (clockwise) until it is tight (See Figure L). Do not overtighten.

{ "type": "p", "children": [], "text": "\nStep 20: Put the mouthpiece back on to your Podhaler device and screw the mouthpiece on by turning it to the right (clockwise) until it is tight (See Figure L). Do not overtighten.\n" }

Step 21: Wipe the mouthpiece with a clean, dry cloth (See Figure W).

{ "type": "p", "children": [], "text": "\nStep 21: Wipe the mouthpiece with a clean, dry cloth (See Figure W)." }

{ "type": "", "children": [], "text": "" }

Step 22: Place your Podhaler device back in the storage case base.

{ "type": "p", "children": [], "text": "\nStep 22: Place your Podhaler device back in the storage case base." }

Step 23: Place the lid back on the storage case base and screw the cover on by turning it to the right (clockwise) until it is tight (See Figure X).

{ "type": "p", "children": [], "text": "\nStep 23: Place the lid back on the storage case base and screw the cover on by turning it to the right (clockwise) until it is tight (See Figure X)." }

How should I store TOBI Podhaler?

{ "type": "p", "children": [], "text": "\nHow should I store TOBI Podhaler?\n" }

{ "type": "", "children": [], "text": "" }

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration." }

© 2020 Mylan Inc.

{ "type": "p", "children": [], "text": "© 2020 Mylan Inc." }

Tobi® and Podhaler® are registered trademarks of BGP Products Operations GmbH, a Mylan company.

{ "type": "p", "children": [], "text": "Tobi® and Podhaler® are registered trademarks of BGP Products Operations GmbH, a Mylan company." }

Manufactured for: Mylan Specialty L.P. Morgantown, WV 26505 U.S.A.

{ "type": "p", "children": [], "text": "Manufactured for:\nMylan Specialty L.P.\nMorgantown, WV 26505 U.S.A." }

Manufactured by: Mylan Pharmaceuticals Inc. 150 Industrial RoadSan Carlos, CA 94070 U.S.A.

{ "type": "p", "children": [], "text": "Manufactured by:\nMylan Pharmaceuticals Inc.\n150 Industrial RoadSan Carlos, CA 94070 U.S.A." }

Revised: 2/2023N:TOBRIP:R4/PI:TOBRIP:R4/IFU:TOBRIP:R2

{ "type": "p", "children": [], "text": "Revised: 2/2023N:TOBRIP:R4/PI:TOBRIP:R4/IFU:TOBRIP:R2" }

NDC 49502-401-24     Rx only

{ "type": "p", "children": [], "text": "\nNDC 49502-401-24     Rx only\n" }

TOBI® Podhaler® (tobramycin inhalation powder)

{ "type": "p", "children": [], "text": "\nTOBI® Podhaler®\n\n(tobramycin inhalation powder)\n" }

28 mg per capsule

{ "type": "p", "children": [], "text": "\n28 mg per capsule" }

For Oral Inhalation Only

{ "type": "p", "children": [], "text": "\nFor Oral Inhalation Only\n" }

Do not swallow TOBI® Podhaler® capsules

{ "type": "p", "children": [], "text": "\nDo not swallow TOBI® Podhaler® capsules\n" }

TOBI® Podhaler® capsules are for use with the Podhaler® device only

{ "type": "p", "children": [], "text": "\nTOBI® Podhaler® capsules are for use with the Podhaler® device only\n" }

This package contains a 4-week supply of capsules:4 weekly packs x 56 capsules per pack

{ "type": "p", "children": [], "text": "This package contains a 4-week supply of capsules:4 weekly packs x 56 capsules per pack" }

Each capsule contains 28 mg tobramycin with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment)

{ "type": "p", "children": [], "text": "Each capsule contains 28 mg tobramycin with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), calcium chloride, and sulfuric acid (for pH adjustment)" }

Dosage: See prescribing information.Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F); protect from moisture.

{ "type": "p", "children": [], "text": "\nDosage: See prescribing information.Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F); protect from moisture." }

Capsules Should Always Be Stored in the Blister and Only Removed Immediately Before Use.

{ "type": "p", "children": [], "text": "Capsules Should Always Be Stored in the Blister and Only Removed Immediately Before Use." }

Always store the Podhaler® device in its case.

{ "type": "p", "children": [], "text": "Always store the Podhaler® device in its case." }

Keep this and all drugs out of the reach of children.

{ "type": "p", "children": [], "text": "Keep this and all drugs out of the reach of children." }

Contents:4 weekly packs, each containing:     56 capsules (7 blister cards of 8 capsules)     1 Podhaler® device     Patient information leaflet1 Reserve Podhaler® devicePrescribing Information

{ "type": "p", "children": [], "text": "Contents:4 weekly packs, each containing:     56 capsules (7 blister cards of 8 capsules)     1 Podhaler® device     Patient information leaflet1 Reserve Podhaler® devicePrescribing Information" }

Product of Hungary

{ "type": "p", "children": [], "text": "Product of Hungary" }

Manufactured for: Mylan Specialty L.P. Morgantown, WV 26505 U.S.A.

{ "type": "p", "children": [], "text": "Manufactured for:\nMylan Specialty L.P.\nMorgantown, WV 26505 U.S.A." }

Manufactured by: Mylan Pharmaceuticals Inc. San Carlos, CA 94070 U.S.A.

{ "type": "p", "children": [], "text": "Manufactured by:\nMylan Pharmaceuticals Inc.\nSan Carlos, CA 94070 U.S.A." }

© 2020 Mylan Inc.

{ "type": "p", "children": [], "text": "© 2020 Mylan Inc." }

GTIN: 00349502401244EXP/LOT

{ "type": "p", "children": [], "text": "GTIN: 00349502401244EXP/LOT" }