Fluticasone Propionate HFA is indicated for the maintenance treatment of asthma as prophylactic therapy in adult and pediatric patients aged 4 years and older.

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Limitations of Use

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Fluticasone Propionate HFA is not indicated for the relief of acute bronchospasm.

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Fluticasone Propionate HFA should be administered by the orally inhaled route only. After inhalation, rinse mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis.

A valved holding chamber and mask may be used to deliver Fluticasone Propionate HFA to young patients.

Priming

Prime Fluticasone Propionate HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well for 5 seconds and releasing 1 spray into the air away from the face. Avoid spraying in eyes.

Adult and Adolescent Patients Aged 12 Years and Older

The recommended starting dosage for patients aged 12 years and older who are not on an inhaled corticosteroid (ICS): 88 mcg (2 inhalations of 44 mcg fluticasone propionate) twice daily by oral inhalation, approximately 12 hours apart.

Pediatric Patients Aged 4 to 11 Years

The recommended dosage for patients aged 4 to 11 years: 88 mcg (2 inhalations of 44 mcg fluticasone propionate) twice daily by oral inhalation, approximately 12 hours apart.

General Dosing Recommendations

The starting dosage is based on previous asthma therapy and asthma severity, including consideration of patients’ current control of asthma symptoms and risk of future exacerbation.

If symptoms arise between doses, an inhaled short-acting beta2-agonist should be used for immediate relief.

Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment.

For other patients, and for patients who do not respond adequately to the starting dosage after 2 weeks of therapy, higher dosages may provide additional asthma control.

If a dosage regimen fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options, e.g., replacing the current strength with a higher strength, initiating an ICS and long-acting beta2-agonist (LABA) combination product, or initiating oral corticosteroids, should be considered.

After asthma stability has been achieved, titrate to the lowest effective dosage to reduce the possibility of side effects.

Inhalation aerosol: dark orange plastic inhaler with a peach cap containing a pressurized metered-dose aerosol canister containing 120 metered inhalations and fitted with a counter.

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Fluticasone Propionate HFA is contraindicated in the following conditions:

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In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with fluticasone propionate HFA. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with Fluticasone Propionate HFA continues, but at times therapy with Fluticasone Propionate HFA may need to be interrupted. Advise the patient to rinse his/her mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.

Fluticasone Propionate HFA is not to be regarded as a bronchodilator and is not indicated for rapid relief of bronchospasm. Patients should be instructed to contact their physicians immediately when episodes of asthma that are not responsive to bronchodilators occur during the course of treatment with Fluticasone Propionate HFA. During such episodes, patients may require therapy with oral corticosteroids.

Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

ICS should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Hypothalamic-Pituitary-Adrenal Suppression/Adrenal Insufficiency

Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available ICS. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

Patients who have been previously maintained on 20 mg or more of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although Fluticasone Propionate HFA may control asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.

During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Fluticasone Propionate HFA. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with Fluticasone Propionate HFA. Lung function (mean forced expiratory volume in 1 second [FEV1] or morning peak expiratory flow [AM PEF]), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition, patients should be observed for signs and symptoms of adrenal insufficiency, such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.

Unmasking of Allergic Conditions Previously Suppressed by Systemic Corticosteroids

Transfer of patients from systemic corticosteroid therapy to Fluticasone Propionate HFA may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions).

Corticosteroid Withdrawal Symptoms

During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression) despite maintenance or even improvement of respiratory function.

Fluticasone propionate will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of Fluticasone Propionate HFA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing Fluticasone Propionate HFA.

Because of the possibility of significant systemic absorption of ICS in sensitive patients, patients treated with Fluticasone Propionate HFA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.

It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients who are sensitive to these effects. If such effects occur, Fluticasone Propionate HFA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of asthma symptoms should be considered.

Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate HFA [see Contraindications (4)].

Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing ICS. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids), should be monitored and treated with established standards of care.

A 2-year trial in 160 subjects (females aged 18 to 40 years, males 18 to 50) with asthma receiving chlorofluorocarbon (CFC)-propelled fluticasone propionate inhalation aerosol 88 or 440 mcg twice daily demonstrated no statistically significant changes in BMD at any time point (24, 52, 76, and 104 weeks of double-blind treatment) as assessed by dual-energy x-ray absorptiometry at lumbar regions L1 through L4.

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving Fluticasone Propionate HFA routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including Fluticasone Propionate HFA, titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration (2.2), Use in Specific Populations (8.4)].

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients following the long-term administration of ICS, including fluticasone propionate. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use Fluticasone Propionate HFA long term.

As with other inhaled medicines, bronchospasm may occur with an immediate increase in wheezing after dosing. If bronchospasm occurs following dosing with Fluticasone Propionate HFA, it should be treated immediately with an inhaled, short-acting bronchodilator; Fluticasone Propionate HFA should be discontinued immediately; and alternative therapy should be instituted.

The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate HFA is not recommended because increased systemic corticosteroid adverse effects may occur [see Drug Interactions (7.1), Clinical Pharmacology (12.3)].

In rare cases, patients on inhaled fluticasone propionate may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other ICS in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.

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

The incidence of common adverse reactions in Table 1 is based upon 2 placebo-controlled U.S. clinical trials in which 812 adult and adolescent subjects (457 females and 355 males) previously treated with as-needed bronchodilators and/or ICS were treated twice daily for up to 12 weeks with 2 inhalations of fluticasone propionate HFA 44 mcg, fluticasone propionate HFA 110 mcg, fluticasone propionate HFA 220 mcg (dosages of 88, 220, or 440 mcg twice daily), or placebo.

<div class="scrollingtable"><table width="99.36%"> <caption> <span>Table 1. Adverse Reactions with Fluticasone Propionate HFA with &gt;3% Incidence and More Common than Placebo in Subjects Aged 12 Years and Older with Asthma </span> </caption> <col width="33%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Adverse Event</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Fluticasone Propionate HFA</span> </p> <p> <span class="Bold">88 mcg</span> </p> <p> <span class="Bold">Twice Daily</span> </p> <p> <span class="Bold">(n = 203)</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Fluticasone Propionate HFA</span> </p> <p> <span class="Bold">220 mcg</span> </p> <p> <span class="Bold">Twice Daily</span> </p> <p> <span class="Bold">(n = 204)</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Fluticasone Propionate HFA</span> </p> <p> <span class="Bold">440 mcg</span> </p> <p> <span class="Bold">Twice Daily</span> </p> <p> <span class="Bold">(n = 202)</span> </p> <p> <span class="Bold">%</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(n = 203)</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Ear, nose, and throat</p> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">     Upper respiratory tract infection</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">18</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">16</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">16</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">14</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">     Throat irritation</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">8</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">8</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">10</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">5</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">     Upper respiratory inflammation</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">2</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">5</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">5</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">1</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">     Sinusitis/sinus infection</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">6</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">7</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">4</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">3</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Hoarseness/dysphonia</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">2</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">3</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">6</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">&lt;1</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Gastrointestinal</p> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Candidiasis mouth/throat and non-site specific</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">4</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">2</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">5</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">&lt;1</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Lower respiratory</p> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">     Cough</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">4</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">6</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">4</p> </td><td align="center" class="Rrule" valign="middle"> <p class="First">5</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Bronchitis</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">2</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">2</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">6</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">5</p> </td> </tr> <tr> <td class="Lrule Rrule" valign="top"> <p class="First">Neurological</p> </td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td><td class="Rrule" valign="middle"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">     Headache</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">11</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">7</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">5</p> </td><td align="center" class="Botrule Rrule" valign="middle"> <p class="First">6</p> </td> </tr> </tbody> </table></div>

Table 1 includes all events (whether considered drug-related or nondrug-related by the investigator) that occurred at a rate of over 3% in any of the groups treated with fluticasone propionate HFA and were more common than in the placebo group. Less than 2% of subjects discontinued from the trials because of adverse reactions. The average duration of exposure was 73 to 76 days in the active treatment groups compared with 60 days in the placebo group.

Additional Adverse Reactions

Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with asthma treated with fluticasone propionate HFA compared with subjects treated with placebo include the following: rhinitis, rhinorrhea/post-nasal drip, nasal sinus disorders, laryngitis, diarrhea, viral gastrointestinal infections, dyspeptic symptoms, gastrointestinal discomfort and pain, hyposalivation, musculoskeletal pain, muscle pain, muscle stiffness/tightness/rigidity, dizziness, migraines, fever, viral infections, pain, chest symptoms, viral skin infections, muscle injuries, soft tissue injuries, urinary infections.

Fluticasone propionate inhalation aerosol (440 or 880 mcg twice daily) was administered for 16 weeks to 168 subjects with asthma requiring oral corticosteroids (Trial 3). Adverse reactions not included above but reported by more than 3 subjects in either group treated with fluticasone propionate HFA and more commonly than in the placebo group included nausea and vomiting, arthralgia and articular rheumatism, and malaise and fatigue.

In 2 long-term trials (26 and 52 weeks), the pattern of adverse reactions in subjects treated with fluticasone propionate HFA at dosages up to 440 mcg twice daily was similar to that observed in the 12-week trials. There were no new and/or unexpected adverse reactions with long-term treatment.

Pediatric Subjects Aged 4 to 11 Years

Fluticasone propionate HFA has been evaluated for safety in 56 pediatric subjects who received 88 mcg twice daily for 4 weeks. Types of adverse reactions in these pediatric subjects were generally similar to those observed in adults and adolescents.

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of fluticasone propionate. 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate or a combination of these factors.

Ear, Nose, and Throat

Aphonia, facial and oropharyngeal edema, and throat soreness and irritation.

Endocrine and Metabolic

Cushingoid features, growth velocity reduction in children/adolescents, hyperglycemia, osteoporosis, and weight gain.

Eye

Cataracts.

Gastrointestinal Disorders

Dental caries and tooth discoloration.

Immune System Disorders

Immediate and delayed hypersensitivity reactions, including urticaria, anaphylaxis, rash, and angioedema and bronchospasm, have been reported.

Infections and Infestations

Esophageal candidiasis.

Psychiatry

Agitation, aggression, anxiety, depression, and restlessness. Behavioral changes, including hyperactivity and irritability, have been reported very rarely and primarily in children.

Respiratory

Asthma exacerbation, chest tightness, cough, dyspnea, immediate and delayed bronchospasm, paradoxical bronchospasm, pneumonia, and wheeze.

Skin

Contusions, cutaneous hypersensitivity reactions, ecchymoses, and pruritus.

Fluticasone propionate is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate HFA is not recommended because increased systemic corticosteroid adverse effects may occur.

Ritonavir

A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology (12.3)]. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.

Ketoconazole

Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol.

Risk Summary

There are insufficient data on the use of fluticasone propionate HFA in pregnant women. There are clinical considerations with the use of fluticasone propionate HFA in pregnant women. (See Clinical Considerations.) In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations in rats, mice, and rabbits, was observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (MRHDID) on a mcg/m2 basis. (See Data.) However, fluticasone propionate administered via inhalation to rats decreased fetal body weight but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m2 basis. (See Data.) Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans.

The estimated risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated 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 Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.

Data

Human Data: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery.

Animal Data: In embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 0.5 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). The rat no observed adverse effect level (NOAEL) was observed at approximately 0.17 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.1 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). The mouse NOAEL was observed with a dose approximately 0.04 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day).

In an embryofetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.14 times the MRHDID (on a mcg/m2 basis with a maternal inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. The NOAEL was observed with a dose approximately 0.03 times the MRHDID (on a mcg/m2 basis with a maternal inhalation dose of 5.5 mcg/kg/day).

In an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.006 times the MRHDID and higher (on a mcg/m2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day). Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose approximately 0.04 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). The NOAEL was observed in rabbit fetuses with a dose approximately 0.001 times the MRHDID (on a mcg/m2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day).

Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.

In a pre- and post-natal development study in pregnant rats dosed from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 0.3 times the MRHDID (on a mcg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day).

Risk Summary

There are no available data on the presence of fluticasone propionate in human milk, the effects on the breastfed child, or the effects on milk production. Other corticosteroids have been detected in human milk. However, fluticasone propionate concentrations in plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low [see Clinical Pharmacology (12.3)]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluticasone propionate HFA and any potential adverse effects on the breastfed child from fluticasone propionate HFA or from the underlying maternal condition.

Data

Animal Data: Subcutaneous administration of tritiated fluticasone propionate at a dose of 10 mcg/kg/day to lactating rats resulted in measurable levels in milk.

The safety and effectiveness of fluticasone propionate HFA in pediatric patients aged 4 years and older have been established [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14.2)]. Use of fluticasone propionate HFA in patients aged 4 to 11 years is supported by evidence from adequate and well-controlled trials in adults and adolescents aged 12 years and older, pharmacokinetic trials in patients aged 4 to 11 years, established efficacy of fluticasone propionate formulated as FLOVENT DISKUS (fluticasone propionate inhalation powder) and FLOVENT ROTADISK (fluticasone propionate inhalation powder) in patients aged 4 to 11 years, and supportive findings with fluticasone propionate HFA in a trial conducted in subjects aged 4 to 11 years.

The safety and effectiveness of fluticasone propionate HFA in pediatric patients younger than 4 years have not been established.

Effects on Growth

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. A reduction of growth velocity in children or teenagers may occur as a result of poorly controlled asthma or from use of corticosteroids including ICS. The effects of long-term treatment of children and adolescents with ICS, including fluticasone propionate, on final adult height are not known.

Controlled clinical trials have shown that ICS may cause a reduction in growth in pediatric patients. In these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appeared to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of HPA axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied. The effects on growth velocity of treatment with orally inhaled corticosteroids for over 1 year, including the impact on final adult height, are unknown. The growth of children and adolescents receiving orally inhaled corticosteroids, including Fluticasone Propionate HFA, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including Fluticasone Propionate HFA, each patient should be titrated to the lowest dose that effectively controls his/her symptoms.

Since a cross trial comparison in adult and adolescent subjects (aged 12 years and older) indicated that systemic exposure of inhaled fluticasone propionate from fluticasone propionate HFA would be higher than exposure from FLOVENT ROTADISK, results from a trial to assess the potential growth effects of FLOVENT ROTADISK in pediatric subjects (aged 4 to 11 years) are provided.

A 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (FLOVENT ROTADISK) at 50 and 100 mcg twice daily was conducted in the U.S. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. The mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89). An imbalance in the proportion of children entering puberty between groups and a higher dropout rate in the placebo group due to poorly controlled asthma may be confounding factors in interpreting these data. A separate subset analysis of children who remained prepubertal during the trial revealed growth rates at 52 weeks of 6.10 cm/year in the placebo group (n = 57), 5.91 cm/year in the 50-mcg group (n = 74), and 5.67 cm/year in the 100-mcg group (n = 79). In children aged 8.5 years, the mean age of children in this trial, the range for expected growth velocity is: boys – 3rd percentile = 3.8 cm/year, 50th percentile = 5.4 cm/year, and 97th percentile = 7.0 cm/year; girls – 3rd percentile = 4.2 cm/year, 50th percentile = 5.7 cm/year, and 97th percentile = 7.3 cm/year. The clinical relevance of these growth data is not certain.

Pediatric Patients Younger than 4 Years

Pharmacokinetics: [see Clinical Pharmacology (12.3)].

Pharmacodynamics: A 12-week, double-blind, placebo-controlled, parallel-group trial was conducted in children with asthma aged 1 to younger than 4 years. Twelve-hour overnight urinary cortisol excretion after a 12-week treatment period with 88 mcg of fluticasone propionate HFA twice daily (n = 73) and with placebo (n = 42) were calculated. The mean and median change from baseline in urine cortisol over 12 hours were -0.7 and 0.0 mcg for fluticasone propionate HFA and 0.3 and -0.2 mcg for placebo, respectively.

In a 1-way crossover trial in children aged 6 to younger than 12 months with reactive airways disease (N = 21), serum cortisol was measured over a 12-hour dosing period. Subjects received placebo treatment for a 2-week period followed by a 4-week treatment period with 88 mcg of fluticasone propionate HFA twice daily with an AeroChamber Plus Valved Holding Chamber (VHC) with mask. The geometric mean ratio of serum cortisol over 12 hours [AUC(0-12 h)] following fluticasone propionate HFA (n = 16) versus placebo (n = 18) was 0.95 (95% CI: 0.72, 1.27).

Safety: Fluticasone propionate HFA administered as 88 mcg twice daily was evaluated for safety in 239 pediatric subjects aged 1 to younger than 4 years in a 12-week, double-blind, placebo-controlled trial. Treatments were administered with an AeroChamber Plus VHC with mask. The following events occurred with a frequency >3% and more frequently in subjects receiving fluticasone propionate HFA than in subjects receiving placebo, regardless of causality assessment: pyrexia, nasopharyngitis, upper respiratory tract infection, vomiting, otitis media, diarrhea, bronchitis, pharyngitis, and viral infection.

Fluticasone propionate HFA administered as 88 mcg twice daily was evaluated for safety in 23 pediatric subjects aged 6 to 12 months in an open-label placebo-controlled trial. Treatments were administered with an AeroChamber Plus VHC with mask for 2 weeks with placebo followed by 4 weeks with active drug. There was no discernable difference in the types of adverse events reported between subjects receiving placebo compared with the active drug.

In Vitro Testing of Dose Delivery with Holding Chambers: In vitro dose characterization studies were performed to evaluate the delivery of fluticasone propionate HFA via holding chambers with attached masks. The studies were conducted with 2 different holding chambers (AeroChamber Plus VHC and AeroChamber Z-STAT Plus VHC) with masks (small and medium size) at inspiratory flow rates of 4.9, 8.0, and 12.0 L/min in combination with holding times of 0, 2, 5, and 10 seconds. The flow rates were selected to be representative of inspiratory flow rates of children aged 6 to 12 months, 2 to 5 years, and over 5 years, respectively. The mean delivered dose of fluticasone propionate through the holding chambers with masks was lower than the 44 mcg of fluticasone propionate delivered directly from the actuator mouthpiece. The results were similar through both holding chambers (see Table 2 for data for the AeroChamber Plus VHC). The fine particle fraction (approximately 1 to 5 μm) across the flow rates used in these studies was 70% to 84% of the delivered dose, consistent with the removal of the coarser fraction by the holding chamber. In contrast, the fine particle fraction for fluticasone propionate HFA delivered without a holding chamber typically represents 42% to 55% of the delivered dose measured at the standard flow rate of 28.3 L/min. These data suggest that, on a per kilogram basis, young children receive a comparable dose of fluticasone propionate when delivered via a holding chamber and mask as adults do without their use.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2. In Vitro Medication Delivery through AeroChamber Plus Valved Holding Chamber with a Mask </span> </caption> <col width="9%"/> <col width="10%"/> <col width="10%"/> <col width="11%"/> <col width="27%"/> <col width="15%"/> <col width="18%"/> <tfoot> <tr class="First Last"> <td align="left" colspan="7" valign="top"><span class="Sup">a</span> Centers for Disease Control growth charts, developed by the National Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention and Health Promotion (2000). Ranges correspond to the average of the 50<span class="Sup">th</span> percentile weight for boys and girls at the ages indicated.<br/> <span class="Sup">b</span> A single inhalation of fluticasone propionate HFA in a 70-kg adult without use of a valved holding chamber and mask delivers approximately 44 mcg, or 0.6 mcg/kg.</td> </tr> </tfoot> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Age</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Mask</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Flow Rate</span> </p> <p> <span class="Bold">(L/min)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Holding Time</span> </p> <p> <span class="Bold">(seconds)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Mean Medication Delivery through AeroChamber</span> </p> <p> <span class="Bold">Plus Valved Holding Chamber</span> </p> <p> <span class="Bold">(mcg/actuation)</span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Body Weight 50<span class="Sup">th</span> Percentile</span> </p> <p> <span class="Bold">(kg)<span class="Sup">a</span></span> </p> </td><td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Medication Delivered per Actuation</span> </p> <p> <span class="Bold">(mcg/kg)<span class="Sup">b</span></span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">6 to 12</p> <p>Months</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Small</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">4.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> <p>2</p> <p>5</p> <p>10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8.3</p> <p>6.7</p> <p>7.5</p> <p>7.5</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7.5-9.9</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.8-1.1</p> <p>0.7-0.9</p> <p>0.8-1.0</p> <p>0.8-1.0</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">2 to 5 </p> <p>Years</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Small</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> <p>2</p> <p>5</p> <p>10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7.3</p> <p>6.8</p> <p>6.7</p> <p>7.7</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12.3-18.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.4-0.6</p> <p>0.4-0.6</p> <p>0.4-0.5</p> <p>0.4-0.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">2 to 5 </p> <p>Years</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Medium</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">8.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> <p>2</p> <p>5</p> <p>10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">7.8</p> <p>7.7</p> <p>8.1</p> <p>9.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12.3-18.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.4-0.6</p> <p>0.4-0.6</p> <p>0.5-0.7</p> <p>0.5-0.7</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">&gt;5 Years</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">Medium</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0</p> <p>2</p> <p>5</p> <p>10</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">12.3</p> <p>11.8</p> <p>12.0</p> <p>10.1</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">18.0</p> </td><td align="center" class="Botrule Lrule Rrule" valign="top"> <p class="First">0.7</p> <p>0.7</p> <p>0.7</p> <p>0.6</p> </td> </tr> </tbody> </table></div>

Of the total number of subjects treated with fluticasone propionate HFA in U.S. and non-U.S. clinical trials, 173 were aged 65 years or older, 19 of which were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Formal pharmacokinetic studies using fluticasone propionate HFA have not been conducted in patients with hepatic impairment. Since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. Therefore, patients with hepatic disease should be closely monitored.

Formal pharmacokinetic studies using fluticasone propionate HFA have not been conducted in patients with renal impairment.

Chronic overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "Chronic overdosage may result in signs/symptoms of hypercorticism [see Warnings and Precautions (5.5)]." }

Fluticasone Propionate HFA is a pressurized metered dose inhaler for oral inhalation. The active component of Fluticasone Propionate HFA 44 mcg, Fluticasone Propionate HFA 110 mcg, and Fluticasone Propionate HFA 220 mcg is fluticasone propionate, a corticosteroid having the chemical name S-(fluoromethyl) 6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate,17-propionate and the following chemical structure:

{ "type": "p", "children": [], "text": "Fluticasone Propionate HFA is a pressurized metered dose inhaler for oral inhalation. The active component of Fluticasone Propionate HFA 44 mcg, Fluticasone Propionate HFA 110 mcg, and Fluticasone Propionate HFA 220 mcg is fluticasone propionate, a corticosteroid having the chemical name S-(fluoromethyl) 6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate,17-propionate and the following chemical structure:" }

Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empirical formula is C25H31F3O5S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol.

{ "type": "p", "children": [], "text": "Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empirical formula is C25H31F3O5S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol." }

Fluticasone Propionate HFA is a dark orange plastic inhaler with a peach cap containing a pressurized metered-dose aerosol canister fitted with a counter. Each canister contains a microcrystalline suspension of micronized fluticasone propionate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no other excipients.

{ "type": "p", "children": [], "text": "Fluticasone Propionate HFA is a dark orange plastic inhaler with a peach cap containing a pressurized metered-dose aerosol canister fitted with a counter. Each canister contains a microcrystalline suspension of micronized fluticasone propionate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no other excipients." }

After priming, each actuation of the inhaler delivers 50, 125, or 250 mcg of fluticasone propionate in 60 mg of suspension (for the 44-mcg product) or in 75 mg of suspension (for the 110- and 220-mcg products) from the valve. Each actuation delivers 44, 110, or 220 mcg of fluticasone propionate from the actuator. The actual amount of drug delivered to the lung will depend on patient factors, such as the coordination between the actuation of the inhaler and inspiration through the delivery system.

{ "type": "p", "children": [], "text": "After priming, each actuation of the inhaler delivers 50, 125, or 250 mcg of fluticasone propionate in 60 mg of suspension (for the 44-mcg product) or in 75 mg of suspension (for the 110- and 220-mcg products) from the valve. Each actuation delivers 44, 110, or 220 mcg of fluticasone propionate from the actuator. The actual amount of drug delivered to the lung will depend on patient factors, such as the coordination between the actuation of the inhaler and inspiration through the delivery system." }

Prime Fluticasone Propionate HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well for 5 seconds and releasing 1 spray into the air away from the face. Avoid spraying in eyes.

{ "type": "p", "children": [], "text": "Prime Fluticasone Propionate HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 7 days or when it has been dropped, prime the inhaler again by shaking well for 5 seconds and releasing 1 spray into the air away from the face. Avoid spraying in eyes." }

Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone propionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is 18 times that of dexamethasone, almost twice that of beclomethasone‑17‑monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results. The clinical significance of these findings is unknown.

Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma.

Though effective for the treatment of asthma, corticosteroids do not affect asthma symptoms immediately. Individual patients will experience a variable time to onset and degree of symptom relief. Maximum benefit may not be achieved for 1 to 2 weeks or longer after starting treatment. When corticosteroids are discontinued, asthma stability may persist for several days or longer.

Trials in subjects with asthma have shown a favorable ratio between topical anti-inflammatory activity and systemic corticosteroid effects with recommended doses of orally inhaled fluticasone propionate. This is explained by a combination of a relatively high local anti-inflammatory effect, negligible oral systemic bioavailability (<1%), and the minimal pharmacological activity of the only metabolite detected in man.

Serum cortisol concentrations, urinary excretion of cortisol, and urine 6-β-hydroxycortisol excretion collected over 24 hours in 24 healthy subjects following 8 inhalations of fluticasone propionate HFA 44, 110, and 220 mcg decreased with increasing dose. However, in patients with asthma treated with 2 inhalations of fluticasone propionate HFA 44, 110, and 220 mcg twice daily for at least 4 weeks, differences in serum cortisol AUC(0-12 h) (n = 65) and 24-hour urinary excretion of cortisol (n = 47) compared with placebo were not related to dose and generally not significant. In the trial with healthy volunteers, the effect of propellant was also evaluated by comparing results following the 220-mcg strength inhaler containing HFA 134a propellant with the same strength of inhaler containing CFC 11/12 propellant. A lesser effect on the HPA axis with the HFA formulation was observed for serum cortisol, but not urine cortisol and 6-betahydroxy cortisol excretion. In addition, in a crossover trial in children with asthma aged 4 to 11 years (N = 40), 24-hour urinary excretion of cortisol was not affected after a 4-week treatment period with 88 mcg of fluticasone propionate HFA twice daily compared with urinary excretion after the 2-week placebo period. The ratio (95% CI) of urinary excretion of cortisol over 24 hours following fluticasone propionate HFA versus placebo was 0.987 (0.796, 1.223).

The potential systemic effects of fluticasone propionate HFA on the HPA axis were also studied in subjects with asthma. Fluticasone propionate given by inhalation aerosol at dosages of 440 or 880 mcg twice daily was compared with placebo in oral corticosteroid-dependent subjects with asthma (range of mean dose of prednisone at baseline: 13 to 14 mg/day) in a 16-week trial. Consistent with maintenance treatment with oral corticosteroids, abnormal plasma cortisol responses to short cosyntropin stimulation (peak plasma cortisol <18 mcg/dL) were present at baseline in the majority of subjects participating in this trial (69% of subjects later randomized to placebo and 72% to 78% of subjects later randomized to fluticasone propionate HFA). At week 16, 8 subjects (73%) on placebo compared with 14 (54%) and 13 (68%) subjects receiving fluticasone propionate HFA (440 and 880 mcg twice daily, respectively) had post-stimulation cortisol levels of <18 mcg/dL.

Absorption

Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.

Distribution

Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 L/kg.

The percentage of fluticasone propionate bound to human plasma proteins averages 99%. Fluticasone propionate is weakly and reversibly bound to erythrocytes and is not significantly bound to human transcortin.

Elimination

Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. The total clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for <0.02% of the total. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.

Metabolism: The only circulating metabolite detected in man is the 17β-carboxylic acid derivative of fluticasone propionate, which is formed through the CYP3A4 pathway. This metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.

Specific Populations

Male and Female Patients: No significant difference in clearance (CL/F) of fluticasone propionate was observed.

Pediatric Patients: A population pharmacokinetic analysis was performed for fluticasone propionate HFA using steady‑state data from 4 controlled clinical trials and single-dose data from 1 controlled clinical trial. The combined cohort for analysis included 269 subjects (161 males and 108 females) with asthma aged 6 months to 66 years who received treatment with fluticasone propionate HFA. Most of these subjects (n = 215) were treated with fluticasone propionate HFA 44 mcg given as 88 mcg twice daily. Fluticasone propionate HFA was delivered using an AeroChamber Plus VHC with a mask to subjects aged younger than 4 years. Data from adult subjects with asthma following fluticasone propionate HFA 110 mcg given as 220 mcg twice daily (n = 15) and following fluticasone propionate HFA 220 mcg given as 440 mcg twice daily (n = 17) at steady state were also included. Data for 22 subjects came from a single-dose crossover study of 264 mcg (6 doses of fluticasone propionate HFA 44 mcg) with and without AeroChamber Plus VHC in children with asthma aged 4 to 11 years.

Stratification of exposure data following fluticasone propionate HFA 88 mcg by age and study indicated that systemic exposure to fluticasone propionate at steady state was similar in children aged 6 to younger than 12 months, children aged 1 to younger than 4 years, and adults and adolescents aged 12 years and older. Exposure was lower in children aged 4 to 11 years, who did not use a VHC, as shown in Table 3.

<div class="scrollingtable"><table width="99.02%"> <caption> <span>Table 3. Systemic Exposure to Fluticasone Propionate following Fluticasone Propionate HFA 88 mcg Twice Daily </span> </caption> <col width="21%"/> <col width="33%"/> <col width="7%"/> <col width="22%"/> <col width="17%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Age</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Valved Holding Chamber</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">AUC<span class="Sub">(0-τ),</span> pg•h/mL</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span>, pg/mL</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">6 to &lt;12 Months</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Yes</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">17</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">141 (88, 227)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">19 (13, 29)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">1 to &lt;4 Years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Yes</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">164</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">143 (131, 157)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">20 (18, 21)</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">4 to 11 Years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">No</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">14</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">68 (48, 97)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">11 (8, 16)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">≥12 Years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">No</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">20</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">149 (106, 210)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">20 (15, 27)</p> </td> </tr> </tbody> </table></div>

The lower exposure to fluticasone propionate in children aged 4 to 11 years who did not use a VHC may reflect the inability to coordinate actuation and inhalation of the metered-dose inhaler. The impact of the use of a VHC on exposure to fluticasone propionate in patients aged 4 to 11 years was evaluated in a single-dose crossover trial with fluticasone propionate HFA 44 mcg given as 264 mcg. In this trial, use of a VHC increased systemic exposure to fluticasone propionate (Table 4), possibly correcting for the inability to coordinate actuation and inhalation.

<div class="scrollingtable"><table width="99.02%"> <caption> <span>Table 4. Systemic Exposure to Fluticasone Propionate following a Single Dose of Fluticasone Propionate HFA 264 mcg </span> </caption> <col width="18%"/> <col width="34%"/> <col width="6%"/> <col width="25%"/> <col width="18%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Age</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">Valved Holding Chamber</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">N</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">AUC<span class="Sub">(0-∞)</span>, pg•h/mL</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td><td align="center" class="Botrule Rrule Toprule" valign="bottom"> <p class="First"> <span class="Bold">C<span class="Sub">max</span>, pg/mL</span> </p> <p> <span class="Bold">(95% CI)</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">4 to 11 Years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">Yes</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">22</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">373 (297, 468)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">61 (51, 73)</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" valign="top"> <p class="First">4 to 11 Years</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">No</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">21</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">141 (111, 178)</p> </td><td align="center" class="Botrule Rrule" valign="top"> <p class="First">23 (19, 28)</p> </td> </tr> </tbody> </table></div>

There was a dose-related increase in systemic exposure in subjects aged 12 years and older receiving higher doses of fluticasone propionate (220 and 440 mcg twice daily). The AUC(0-τ) in pg•h/mL was 358 (95% CI: 272, 473) and 640 (95% CI: 477, 858), and Cmax in pg/mL was 47.3 (95% CI: 37, 61) and 87 (95% CI: 68, 112) following fluticasone propionate 220 and 440 mcg, respectively.

Patients with Hepatic and Renal Impairment: Formal pharmacokinetic studies using fluticasone propionate HFA have not been conducted in patients with hepatic or renal impairment. However, since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. Therefore, patients with hepatic disease should be closely monitored.

Racial or Ethnic Groups: No significant difference in clearance (CL/F) of fluticasone propionate in Caucasian, African‑American, Asian, or Hispanic populations was observed.

Drug Interaction Studies

Inhibitors of Cytochrome P450 3A4: Ritonavir: Fluticasone propionate is a substrate of CYP3A4. Coadministration of fluticasone propionate and the strong CYP3A4 inhibitor ritonavir is not recommended based upon a multiple-dose, crossover drug interaction trial in 18 healthy subjects. Fluticasone propionate aqueous nasal spray (200 mcg once daily) was coadministered for 7 days with ritonavir (100 mg twice daily). Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (<10 pg/mL) in most subjects, and when concentrations were detectable, peak levels (Cmax) averaged 11.9 pg/mL (range: 10.8 to 14.1 pg/mL) and AUC(0-τ) averaged 8.43 pg•h/mL (range: 4.2 to 18.8 pg•h/mL). Fluticasone propionate Cmax and AUC(0-τ) increased to 318 pg/mL (range: 110 to 648 pg/mL) and 3,102.6 pg•h/mL (range: 1,207.1 to 5,662.0 pg•h/mL), respectively, after coadministration of ritonavir with fluticasone propionate aqueous nasal spray. This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in serum cortisol AUC.

Ketoconazole: In a placebo-controlled crossover trial in 8 healthy adult volunteers, coadministration of a single dose of orally inhaled fluticasone propionate (1,000 mcg) with multiple doses of ketoconazole (200 mg) to steady state resulted in increased plasma fluticasone propionate exposure, a reduction in plasma cortisol AUC, and no effect on urinary excretion of cortisol.

Following orally inhaled fluticasone propionate alone, AUC(2-last) averaged 1.559 ng•h/mL (range: 0.555 to 2.906 ng•h/mL) and AUC(2-∞) averaged 2.269 ng•h/mL (range: 0.836 to 3.707 ng•h/mL). Fluticasone propionate AUC(2-last) and AUC(2-∞) increased to 2.781 ng•h/mL (range: 2.489 to 8.486 ng•h/mL) and 4.317 ng•h/mL (range: 3.256 to 9.408 ng•h/mL), respectively, after coadministration of ketoconazole with orally inhaled fluticasone propionate. This increase in plasma fluticasone propionate concentration resulted in a decrease (45%) in serum cortisol AUC.

Erythromycin: In a multiple-dose drug interaction trial, coadministration of orally inhaled fluticasone propionate (500 mcg twice daily) and erythromycin (333 mg 3 times daily) did not affect fluticasone propionate pharmacokinetics.

Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 3 and 10 times the MRHDID for adults and children aged 4 to 11 years, respectively, on a mcg/m2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 0.3 times and approximately equivalent to the MRHDID for adults and children aged 4 to 11 years, respectively, on a mcg/m2 basis) for 104 weeks.

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the in vivo mouse micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.3 times the MRHDID for adults on a mcg/m2 basis).

Three randomized, double-blind, parallel-group, placebo-controlled, U.S. clinical trials were conducted in 980 adult and adolescent subjects (aged 12 years and older) with asthma to assess the efficacy and safety of fluticasone propionate HFA in the treatment of asthma. Fixed dosages of 88, 220, and 440 mcg twice daily (each dose administered as 2 inhalations of the 44-, 110-, and 220-mcg strengths, respectively) and 880 mcg twice daily (administered as 4 inhalations of the 220-mcg strength) were compared with placebo to provide information about appropriate dosing to cover a range of asthma severity. Subjects in these trials included those inadequately controlled with bronchodilators alone (Trial 1), those already receiving ICS (Trial 2), and those requiring oral corticosteroid therapy (Trial 3). In all 3 trials, subjects were allowed to use VENTOLIN (albuterol, USP) Inhalation Aerosol as needed for relief of acute asthma symptoms. In Trials 1 and 2, other maintenance asthma therapies were discontinued.

Trial 1 enrolled 397 subjects with asthma inadequately controlled on bronchodilators alone. Fluticasone propionate HFA was evaluated at dosages of 88, 220, and 440 mcg twice daily for 12 weeks. Baseline FEV1 values were similar across groups (mean 67% of predicted normal). All 3 dosages of fluticasone propionate HFA demonstrated a statistically significant improvement in lung function as measured by improvement in AM pre-dose FEV1 compared with placebo. This improvement was observed after the first week of treatment and was maintained over the 12-week treatment period.

At Endpoint (last observation), mean change from baseline in AM pre-dose percent predicted FEV1 was greater in all 3 groups treated with fluticasone propionate HFA (9.0% to 11.2%) compared with the placebo group (3.4%). The mean differences between the groups treated with fluticasone propionate HFA 88, 220, and 440 mcg and the placebo group were statistically significant, and the corresponding 95% confidence intervals were (2.2%, 9.2%), (2.8%, 9.9%), and (4.3%, 11.3%), respectively.

Figure 1 displays results of pulmonary function tests (mean percent change from baseline in FEV1 prior to AM dose) for the recommended starting dosage of fluticasone propionate HFA (88 mcg twice daily) and placebo from Trial 1. This trial used predetermined criteria for lack of efficacy (indicators of worsening asthma), resulting in withdrawal of more subjects in the placebo group. Therefore, pulmonary function results at Endpoint (the last evaluable FEV1 result, including most subjects’ lung function data) are also displayed.

Figure 1. A 12-Week Clinical Trial in Subjects Aged 12 Years and Older Inadequately Controlled on Bronchodilators Alone: Mean Percent Change from Baseline in FEV1 Prior to AM Dose (Trial 1)

In Trial 2, fluticasone propionate HFA at dosages of 88, 220, and 440 mcg twice daily was evaluated over 12 weeks of treatment in 415 subjects with asthma who were already receiving an ICS at a daily dose within its recommended dose range in addition to as-needed albuterol. Baseline FEV1 values were similar across groups (mean 65% to 66% of predicted normal). All 3 dosages of fluticasone propionate HFA demonstrated a statistically significant improvement in lung function, as measured by improvement in FEV1, compared with placebo. This improvement was observed after the first week of treatment and was maintained over the 12-week treatment period. Discontinuations from the trial for lack of efficacy (defined by a pre-specified decrease in FEV1 or PEF, or an increase in use of VENTOLIN or nighttime awakenings requiring treatment with VENTOLIN) were lower in the groups treated with fluticasone propionate HFA (6% to 11%) compared with placebo (50%).

At Endpoint (last observation), mean change from baseline in AM pre-dose percent predicted FEV1 was greater in all 3 groups treated with fluticasone propionate HFA (2.2% to 4.6%) compared with the placebo group (-8.3%). The mean differences between the groups treated with fluticasone propionate HFA 88, 220, and 440 mcg and the placebo group were statistically significant, and the corresponding 95% confidence intervals were (7.1%, 13.8%), (8.2%, 14.9%), and (9.6%, 16.4%), respectively.

Figure 2 displays the mean percent change from baseline in FEV1 from Week 1 through Week 12. This trial also used predetermined criteria for lack of efficacy, resulting in withdrawal of more subjects in the placebo group; therefore, pulmonary function results at Endpoint are also displayed.

Figure 2. A 12-Week Clinical Trial in Subjects Aged 12 Years and Older Already Receiving Daily Inhaled Corticosteroids: Mean Percent Change from Baseline in FEV1 Prior to AM Dose (Trial 2)

In both trials, use of VENTOLIN, AM and PM PEF, and asthma symptom scores showed numerical improvement with fluticasone propionate HFA compared with placebo.

Trial 3 enrolled 168 subjects with asthma requiring oral prednisone therapy (average baseline daily prednisone dose ranged from 13 to 14 mg). Fluticasone propionate HFA at dosages of 440 and 880 mcg twice daily was evaluated over a 16-week treatment period. Baseline FEV1 values were similar across groups (mean 59% to 62% of predicted normal). Over the course of the trial, subjects treated with either dosage of fluticasone propionate HFA required a statistically significantly lower mean daily oral prednisone dose (6 mg) compared with placebo-treated subjects (15 mg). Both dosages of fluticasone propionate HFA enabled a larger percentage of subjects (59% and 56% in the groups treated with fluticasone propionate HFA 440 and 880 mcg, respectively, twice daily) to eliminate oral prednisone as compared with placebo (13%) (see Figure 3). There was no efficacy advantage of fluticasone propionate HFA 880 mcg twice daily compared with 440 mcg twice daily. Accompanying the reduction in oral corticosteroid use, subjects treated with either dosage of fluticasone propionate HFA had statistically significantly improved lung function, fewer asthma symptoms, and less use of VENTOLIN Inhalation Aerosol compared with the placebo-treated subjects.

Figure 3. A 16-Week Clinical Trial in Subjects Aged 12 Years and Older Requiring Chronic Oral Prednisone Therapy: Change in Maintenance Prednisone Dose

Two long-term safety trials (Trial 4 and Trial 5) of ≥6 months’ duration were conducted in 507 adult and adolescent subjects with asthma. Trial 4 was designed to monitor the safety of 2 doses of fluticasone propionate HFA, while Trial 5 compared fluticasone propionate HFA with fluticasone propionate CFC. Trial 4 enrolled 182 subjects who were treated daily with low to high doses of ICS, beta-agonists (short-acting [as needed or regularly scheduled] or long-acting), theophylline, inhaled cromolyn or nedocromil sodium, leukotriene receptor antagonists, or 5-lipoxygenase inhibitors at baseline. Fluticasone propionate HFA at dosages of 220 and 440 mcg twice daily was evaluated over a 26-week treatment period in 89 and 93 subjects, respectively. Trial 5 enrolled 325 subjects who were treated daily with moderate to high doses of ICS, with or without concurrent use of salmeterol or albuterol, at baseline. Fluticasone propionate HFA at a dosage of 440 mcg twice daily and fluticasone propionate CFC at a dosage of 440 mcg twice daily were evaluated over a 52-week treatment period in 163 and 162 subjects, respectively. Baseline FEV1 values were similar across groups (mean 81% to 84% of predicted normal). Throughout the 52-week treatment period, asthma control was maintained with both formulations of fluticasone propionate compared with baseline. In both trials, none of the subjects were withdrawn due to lack of efficacy.

A 12-week clinical trial conducted in 241 pediatric subjects with asthma was supportive of efficacy but inconclusive due to measurable levels of fluticasone propionate in 6/48 (13%) of the plasma samples from subjects randomized to placebo. Efficacy in subjects aged 4 to 11 years is extrapolated from adult data with fluticasone propionate HFA and other supporting data [see Use in Specific Populations (8.4)].

Fluticasone Propionate HFA is supplied in the following boxes of 1 as a pressurized aluminum canister fitted with a counter and supplied with a dark orange actuator with a peach cap:

{ "type": "p", "children": [], "text": "Fluticasone Propionate HFA is supplied in the following boxes of 1 as a pressurized aluminum canister fitted with a counter and supplied with a dark orange actuator with a peach cap:" }

Fluticasone Propionate HFA 44 mcg: 10.6-g canister containing 120 actuations NDC 68788-8762-1

{ "type": "p", "children": [], "text": "Fluticasone Propionate HFA 44 mcg: 10.6-g canister containing 120 actuations NDC 68788-8762-1\n" }

Each inhaler is packaged with a Patient Information leaflet.

{ "type": "p", "children": [], "text": "Each inhaler is packaged with a Patient Information leaflet. " }

The dark orange actuator supplied with Fluticasone Propionate HFA should not be used with any other product canisters, and actuators from other products should not be used with a Fluticasone Propionate HFA canister.

{ "type": "p", "children": [], "text": "The dark orange actuator supplied with Fluticasone Propionate HFA should not be used with any other product canisters, and actuators from other products should not be used with a Fluticasone Propionate HFA canister." }

Counter

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

Fluticasone Propionate HFA has a counter attached to the canister. The counter starts at 124 and counts down each time a spray is released. The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000.

{ "type": "p", "children": [], "text": "Fluticasone Propionate HFA has a counter attached to the canister. The counter starts at 124 and counts down each time a spray is released. The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000." }

Contents under Pressure

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

Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator.

{ "type": "p", "children": [], "text": "Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator." }

Storage

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Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use.

{ "type": "p", "children": [], "text": "Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use." }

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)." }

Oropharyngeal Candidiasis

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

Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with Fluticasone Propionate HFA, but at times therapy with Fluticasone Propionate HFA may need to be temporarily interrupted under close medical supervision. Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk of thrush. [See Warnings and Precautions (5.1).]

{ "type": "p", "children": [], "text": "Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients. If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with Fluticasone Propionate HFA, but at times therapy with Fluticasone Propionate HFA may need to be temporarily interrupted under close medical supervision. Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk of thrush. [See Warnings and Precautions (5.1).]\n" }

Status Asthmaticus and Acute Asthma Symptoms

{ "type": "p", "children": [], "text": "\nStatus Asthmaticus and Acute Asthma Symptoms\n" }

Inform patients that Fluticasone Propionate HFA is not a bronchodilator and is not intended for use as rescue medicine for acute asthma exacerbations. Advise patients to treat acute asthma symptoms with an inhaled, short-acting beta2-agonist such as albuterol. Instruct patients to contact their physicians immediately if there is deterioration of their asthma. [See Warnings and Precautions (5.2).]

{ "type": "p", "children": [], "text": "Inform patients that Fluticasone Propionate HFA is not a bronchodilator and is not intended for use as rescue medicine for acute asthma exacerbations. Advise patients to treat acute asthma symptoms with an inhaled, short-acting beta2-agonist such as albuterol. Instruct patients to contact their physicians immediately if there is deterioration of their asthma. [See Warnings and Precautions (5.2).]\n" }

Immunosuppression and Risk of Infections

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Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. [See Warnings and Precautions (5.3).]

{ "type": "p", "children": [], "text": "Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. [See Warnings and Precautions (5.3).]\n" }

Hypercorticism and Adrenal Suppression

{ "type": "p", "children": [], "text": "\nHypercorticism and Adrenal Suppression\n" }

Advise patients that Fluticasone Propionate HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, inform patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Patients should taper slowly from systemic corticosteroids if transferring to Fluticasone Propionate HFA. [See Warnings and Precautions (5.5).]

{ "type": "p", "children": [], "text": "Advise patients that Fluticasone Propionate HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, inform patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Patients should taper slowly from systemic corticosteroids if transferring to Fluticasone Propionate HFA. [See Warnings and Precautions (5.5).]\n" }

Hypersensitivity Reactions, including Anaphylaxis

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions, including Anaphylaxis\n" }

Advise patients that immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate HFA. Patients should discontinue Fluticasone Propionate HFA if such reactions occur. [See Warnings and Precautions (5.6).]

{ "type": "p", "children": [], "text": "Advise patients that immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate HFA. Patients should discontinue Fluticasone Propionate HFA if such reactions occur. [See Warnings and Precautions (5.6).]\n" }

Reduction in Bone Mineral Density

{ "type": "p", "children": [], "text": "\nReduction in Bone Mineral Density\n" }

Advise patients who are at an increased risk for decreased BMD that the use of corticosteroids may pose an additional risk. [See Warnings and Precautions (5.7).]

{ "type": "p", "children": [], "text": "Advise patients who are at an increased risk for decreased BMD that the use of corticosteroids may pose an additional risk. [See Warnings and Precautions (5.7).]\n" }

Reduced Growth Velocity

{ "type": "p", "children": [], "text": "\nReduced Growth Velocity\n" }

Inform patients that orally inhaled corticosteroids, including Fluticasone Propionate HFA, may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route. [See Warnings and Precautions (5.8).]

{ "type": "p", "children": [], "text": "Inform patients that orally inhaled corticosteroids, including Fluticasone Propionate HFA, may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route. [See Warnings and Precautions (5.8).]\n" }

Glaucoma and Cataracts

{ "type": "p", "children": [], "text": "\nGlaucoma and Cataracts\n" }

Advise patients that long-term use of ICS may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations. [See Warnings and Precautions (5.9).]

{ "type": "p", "children": [], "text": "Advise patients that long-term use of ICS may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations. [See Warnings and Precautions (5.9).]\n" }

Use Daily for Best Effect

{ "type": "p", "children": [], "text": "\nUse Daily for Best Effect\n" }

Patients should use Fluticasone Propionate HFA at regular intervals as directed. Individual patients will experience a variable time to onset and degree of symptom relief and the full benefit may not be achieved until treatment has been administered for 1 to 2 weeks or longer. Patients should not increase the prescribed dosage but should contact their physicians if symptoms do not improve or if the condition worsens. Instruct patients not to stop use of Fluticasone Propionate HFA abruptly. Patients should contact their physicians immediately if they discontinue use of Fluticasone Propionate HFA.

{ "type": "p", "children": [], "text": "Patients should use Fluticasone Propionate HFA at regular intervals as directed. Individual patients will experience a variable time to onset and degree of symptom relief and the full benefit may not be achieved until treatment has been administered for 1 to 2 weeks or longer. Patients should not increase the prescribed dosage but should contact their physicians if symptoms do not improve or if the condition worsens. Instruct patients not to stop use of Fluticasone Propionate HFA abruptly. Patients should contact their physicians immediately if they discontinue use of Fluticasone Propionate HFA." }

Trademarks are owned by or licensed to the GSK group of companies. The other brands listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed to the GSK group of companies. The makers of these brands are not affiliated with and do not endorse the GSK group of companies or its products.

{ "type": "p", "children": [], "text": "Trademarks are owned by or licensed to the GSK group of companies. The other brands listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed to the GSK group of companies. The makers of these brands are not affiliated with and do not endorse the GSK group of companies or its products." }

Manufactured for: Prasco Laboratories Mason, OH 45040 USA

{ "type": "p", "children": [], "text": "Manufactured for:\nPrasco Laboratories\nMason, OH 45040 USA" }

Manufactured by:GlaxoSmithKlineDurham, NC 27701

{ "type": "p", "children": [], "text": "Manufactured by:GlaxoSmithKlineDurham, NC 27701" }

FLH-PS:4PI

{ "type": "p", "children": [], "text": "FLH-PS:4PI" }

Relabeled By: Preferred Pharmaceuticals Inc.

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

<div class="scrollingtable"><table width="100%"> <col width="31%"/> <col width="31%"/> <col width="38%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule" colspan="3" valign="top"> <p class="First"> <span class="Bold">INSTRUCTIONS FOR USE</span> </p> <p> <span class="Bold">Fluticasone Propionate HFA inhalation aerosol</span> </p> <p> <span class="Bold">for oral inhalation use</span> </p> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Your Fluticasone Propionate HFA inhaler</span> </p> </td> </tr> <tr> <td align="center" class="Lrule" valign="top"><a name="id-1197085643"></a><img alt="Figure A" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-05.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p class="First"> <span class="Bold">Figure A</span> </p> </td><td class="Rrule" colspan="2" valign="top"> <dl> <dt>•</dt> <dd>The metal canister holds the medicine. <span class="Bold">See Figure A.</span> </dd> <dt>•</dt> <dd>The metal canister has a counter to show how many sprays of medicine you have left. The number shows through a window in the back of the dark orange plastic actuator. <span class="Bold">See Figure A.</span> </dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <dl> <dt>•</dt> <dd>The counter starts at <span class="Bold">124</span>. The number will count down by 1 each time you spray the inhaler. The counter will stop counting at <span class="Bold">000</span>.</dd> <dt>•</dt> <dd> <span class="Bold">Do not try to change the numbers or take the counter off the metal canister.</span> The counter cannot be reset, and it is permanently attached to the metal canister.</dd> <dt>•</dt> <dd>The dark orange plastic actuator sprays the medicine from the metal canister. The plastic actuator has a peach protective cap that covers the mouthpiece. <span class="Bold">See Figure A.</span> Keep the protective cap on the mouthpiece when the metal canister is not in use.</dd> <dt>•</dt> <dd> <span class="Bold">Do not</span> use the plastic actuator with a canister of medicine from any other inhaler.</dd> <dt>•</dt> <dd> <span class="Bold">Do not</span> use a Fluticasone Propionate HFA metal canister with an actuator from any other inhaler.</dd> </dl> <p class="First"> <span class="Bold">Before using your Fluticasone Propionate HFA inhaler</span> </p> <dl> <dt>•</dt> <dd>The inhaler should be at room temperature before you use it.</dd> <dt>•</dt> <dd>If a child needs help using the inhaler, an adult should help the child use the inhaler with or without a valved holding chamber, which may also be attached to a mask. The adult should follow the instructions that came with the valved holding chamber. An adult should watch a child use the inhaler to be sure it is used correctly.</dd> </dl> <p> <span class="Bold">Priming your Fluticasone Propionate HFA inhaler</span> </p> </td> </tr> <tr> <td align="center" class="Lrule" valign="top"><a name="id3263"></a><img alt="Figure B" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-06.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p class="First"> <span class="Bold">Figure B</span> </p> <a name="id1115642004"></a><img alt="Figure C" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-07.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p> <span class="Bold">Figure C</span> </p> <a name="id-2138402536"></a><img alt="Figure D" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-08.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p> <span class="Bold">Figure D</span> </p> </td><td class="Rrule" colspan="2" valign="top"> <dl> <dt> </dt> <dd>Before you use Fluticasone Propionate HFA for the first time, you must prime the inhaler so that you will get the right amount of medicine when you use it.</dd> </dl> <dl> <dt>•</dt> <dd>To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out. <span class="Bold">See Figure B.</span> </dd> <dt>•</dt> <dd>Shake the inhaler well for 5 seconds. </dd> <dt>•</dt> <dd>Spray the inhaler 1 time into the air away from your face. <span class="Bold">Avoid spraying in eyes. See Figure C.</span> </dd> <dt>•</dt> <dd>Shake and spray the inhaler like this 3 more times to finish priming it. The counter should now read <span class="Bold">120</span>. <span class="Bold">See Figure D.</span> </dd> <dt>•</dt> <dd>You must prime your inhaler again if you have not used it in more than 7 days or if you have dropped it. To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out. Shake the inhaler well for 5 seconds. Then spray it 1 time into the air away from your face.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">How to use your Fluticasone Propionate HFA inhaler </span> </p> <p> <span class="Bold">Follow these steps every time you use Fluticasone Propionate HFA.</span> </p> </td> </tr> <tr> <td align="center" class="Lrule" rowspan="8" valign="top"><a name="id370730492"></a><img alt="Figure E" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-09.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p class="First"> <span class="Bold">Figure E</span> </p> <a name="id-81764728"></a><img alt="Figure F" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-10.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p> <span class="Bold">Figure F</span> </p> <a name="id533085909"></a><img alt="Figure G" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-11.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p> <span class="Bold">Figure G </span> </p> <a name="id-299923118"></a><img alt="Figure H" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-12.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p> <span class="Bold">Figure H</span> </p> </td><td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 1.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>Make sure the metal canister fits firmly in the plastic actuator. The counter should show through the window in the plastic actuator.</dd> <dt> </dt> <dd>To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out.</dd> <dt> </dt> <dd>Look inside the mouthpiece for foreign objects and take out any you see.</dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 2.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>Hold the inhaler with the mouthpiece down and <span class="Bold">shake it well for 5 seconds</span>. <span class="Bold">See Figure E.</span> </dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 3.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>Breathe out through your mouth and push as much air from your lungs as you can. <span class="Bold">See Figure F.</span> </dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 4.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>Put the mouthpiece in your mouth and close your lips around it. Push the top of the metal canister firmly<span class="Bold"> all the way down</span> while you breathe in deeply and slowly through your mouth. <span class="Bold">See Figure G.</span> </dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 5.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>After the spray comes out, take your finger off the metal canister. After you have breathed in all the way, take the inhaler out of your mouth and close your mouth.</dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 6.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Hold your breath for about 10 seconds,</span> or for as long as is comfortable. <span class="Bold">Breathe out slowly as long as you can.</span> </dd> <dt> </dt> <dd>Wait about 30 seconds and shake the inhaler well for 5 seconds. Repeat Step 2 through Step 6.</dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 7.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Rinse your mouth with water after breathing in the medicine.</span> Spit out the water. Do not swallow it. <span class="Bold">See Figure H.</span> </dd> </dl> </td> </tr> <tr> <td valign="top"> <dl> <dt> </dt> <dd> <span class="Bold">Step 8.</span> </dd> </dl> </td><td class="Rrule" valign="top"> <dl> <dt> </dt> <dd>Put the cap back on the mouthpiece after you finish using the inhaler. Make sure it snaps firmly into place.</dd> </dl> </td> </tr> <tr> <td class="Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Cleaning your Fluticasone Propionate HFA inhaler</span> </p> </td> </tr> <tr> <td align="center" class="Lrule" rowspan="6" valign="top"><a name="id-86312484"></a><img alt="Figure I" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-13.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p class="First"> <span class="Bold">Figure I</span> </p> <a name="id1864939930"></a><img alt="Figure J" src="/dailymed/image.cfm?name=fluticasonepropionatehfa-spl-graphic-14.jpg&amp;setid=ff1cf174-ae6f-45f0-a081-26a34e55f9ea"/><p> <span class="Bold">Figure J</span> </p> </td><td class="Rrule" colspan="2" valign="top"> <p class="First"> <span class="Bold">Clean your inhaler at least 1 time each week after your evening dose.</span> You may not see any medicine build-up on the inhaler, but it is important to keep it clean so medicine build-up will not block the spray. <span class="Bold">See Figure I.</span> </p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Step 9.</span> </p> </td><td class="Rrule" valign="top"> <p class="First">Take the cap off the mouthpiece by squeezing the sides of the cap and pulling it straight out. Do not take the metal canister out of the plastic actuator.</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Step 10.</span> </p> </td><td class="Rrule" valign="top"> <p class="First">Use a clean cotton swab dampened with water to clean the small circular opening where the medicine sprays out of the metal canister. Gently twist the swab in a circular motion to take off any medicine. <span class="Bold">See Figure J. </span>Repeat with a new swab dampened with water to take off any medicine still at the opening.</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Step 11.</span> </p> </td><td class="Rrule" valign="top"> <p class="First">Wipe the inside of the mouthpiece with a clean tissue dampened with water. Let the plastic actuator air-dry overnight.</p> </td> </tr> <tr> <td valign="top"> <p class="First"> <span class="Bold">Step 12.</span> </p> </td><td class="Rrule" valign="top"> <p class="First">Put the cap back on the mouthpiece after the plastic actuator has dried.</p> </td> </tr> <tr> <td class="Rrule" colspan="2" valign="top"></td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule" colspan="3" valign="top"> <p class="First"> <span class="Bold">Replacing your Fluticasone Propionate HFA inhaler</span> </p> <dl> <dt>•</dt> <dd> <span class="Bold">When the counter reads 020</span>, you should refill your prescription or ask your healthcare provider if you need another prescription for Fluticasone Propionate HFA.</dd> <dt>•</dt> <dd> <span class="Bold">When the counter reads 000, throw the inhaler away.</span> You should not keep using the inhaler when the counter reads <span class="Bold">000</span> because you may not receive the right amount of medicine.</dd> <dt>•</dt> <dd> <span class="Bold">Do not use the inhaler</span> after the expiration date, which is on the packaging it comes in.</dd> </dl> <p> <span class="Bold">For correct use of your Fluticasone Propionate HFA inhaler, remember:</span> </p> <dl> <dt>•</dt> <dd>The metal canister should always fit firmly in the plastic actuator.</dd> <dt>•</dt> <dd> <span class="Bold">Shake the inhaler well</span> for 5 seconds before each spray.</dd> <dt>•</dt> <dd>Breathe in deeply and slowly to make sure you get all the medicine.</dd> <dt>•</dt> <dd>Hold your breath for about 10 seconds after breathing in the medicine. Then breathe out fully.</dd> <dt>•</dt> <dd>After each dose, rinse your mouth with water and spit it out. <span class="Bold">Do not</span> swallow the water.</dd> <dt>•</dt> <dd> <span class="Bold">Do not</span> take the inhaler apart.</dd> <dt>•</dt> <dd>Always keep the protective cap on the mouthpiece when your inhaler is not in use. </dd> <dt>•</dt> <dd>Always store your inhaler with the mouthpiece pointing down.</dd> <dt>•</dt> <dd>Clean your inhaler at least 1 time each week.</dd> </dl> <p>For more information about Fluticasone Propionate HFA, call 1-866-525-0688.</p> <p>Trademarks are owned by or licensed to the GSK group of companies.</p> <p>Manufactured for:</p> <p> <span class="Bold">Prasco Laboratories</span> </p> <p>Mason, OH 45040 USA</p> <p>Manufactured by:</p> <p>GlaxoSmithKline </p> <p>Durham, NC 27701</p> <p>FLH-PS:5IFU</p> </td> </tr> </tbody> </table></div>

PRINCIPAL DISPLAY PANEL

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NDC 68788-8762-1

{ "type": "p", "children": [], "text": "\nNDC 68788-8762-1\n" }

Fluticasone Propionate HFA

{ "type": "p", "children": [], "text": "\nFluticasone Propionate HFA \n" }

Inhalation Aerosol 44 mcg

{ "type": "p", "children": [], "text": "\nInhalation Aerosol 44 mcg \n" }

PRASCO

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

Relabeled By: Preferred Pharmaceuticals Inc.

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

For oral inhalation with Fluticasone Propionate HFA actuator only.

{ "type": "p", "children": [], "text": "\nFor oral inhalation with Fluticasone Propionate HFA actuator only.\n" }

Contents: Each canister contains a microcrystalline suspension of fluticasone propionate (micronized) in propellant HFA-134a (1,1,1,2-tetrafluorethane).

{ "type": "p", "children": [], "text": "\nContents: Each canister contains a microcrystalline suspension of fluticasone propionate (micronized) in propellant HFA-134a (1,1,1,2-tetrafluorethane)." }

Each actuation of the inhaler delivers 50 mcg of fluticasone propionate from the valve and 44 mcg from the actuator.

{ "type": "p", "children": [], "text": "Each actuation of the inhaler delivers 50 mcg of fluticasone propionate from the valve and 44 mcg from the actuator." }

Net Wt. 10.6 g

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120 Metered Actuations

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Rx only

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Made in Singapore

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Fluticasone propionate nasal spray is indicated for the management of the nasal symptoms of perennial nonallergic rhinitis in adults and pediatric patients aged 4 years and older.

{ "type": "p", "children": [], "text": "Fluticasone propionate nasal spray is indicated for the management of the nasal symptoms of perennial nonallergic rhinitis in adults and pediatric patients aged 4 years and older." }

The recommended starting dosage in adults is 2 sprays (50 mcg of fluticasone propionate each) in each nostril once daily (total daily dose, 200 mcg). The same total daily dose, 1 spray in each nostril administered twice daily (e.g., 8 a.m. and 8 p.m.) is also effective. After the first few days, patients may be able to reduce their dose to 1 spray in each nostril once daily for maintenance therapy.

Maximum total daily doses should not exceed 2 sprays in each nostril (total dose, 200 mcg/day). There is no evidence that exceeding the recommended dose is more effective.

The recommended starting dosage in adolescents and children, aged 4 years and older is 1 spray in each nostril once daily (total daily dose, 100 mcg). Patients not adequately responding to 1 spray in each nostril may use 2 sprays in each nostril once daily (total daily dose, 200 mcg). Once adequate control is achieved, the dosage should be decreased to 1 spray in each nostril once daily.

The maximum total daily dosage should not exceed 2 sprays in each nostril (200 mcg/day). There is no evidence that exceeding the recommended dose is more effective.

Fluticasone propionate nasal spray USP is an aqueous suspension. Each 100-mg spray delivers 50 mcg of fluticasone propionate USP.

{ "type": "p", "children": [], "text": "Fluticasone propionate nasal spray USP is an aqueous suspension. Each 100-mg spray delivers 50 mcg of fluticasone propionate USP." }

Fluticasone propionate nasal spray is contraindicated in patients with hypersensitivity to any of its ingredients [see Warnings and Precautions ( 5.3), Description ( 11)] .

{ "type": "p", "children": [], "text": "Fluticasone propionate nasal spray is contraindicated in patients with hypersensitivity to any of its ingredients\n \n [see Warnings and Precautions (\n \n 5.3), Description (\n \n 11)]\n \n .\n\n " }

Epistaxis

In clinical trials of 2 to 26 weeks’ duration, epistaxis was observed more frequently in subjects treated with fluticasone propionate nasal spray than those who received placebo [See Adverse Reactions ( 6.1)] .

Nasal Ulceration

Postmarketing cases of nasal ulceration have been reported in patients treated with fluticasone propionate nasal spray [see Adverse Reactions ( 6.2)] .

CandidaInfection

In clinical trials with fluticasone propionate administered intranasally, the development of localized infections of the nose and pharynx with  Candida albicans has occurred. When such an infection develops, it may require treatment with appropriate local therapy and discontinuation of fluticasone propionate nasal spray. Patients using fluticasone propionate nasal spray over several months or longer should be examined periodically for evidence of  Candida infection or other signs of adverse effects on the nasal mucosa.

Nasal Septal Perforation

Postmarketing cases of nasal septal perforation have been reported in patients treated with fluticasone propionate nasal spray  [see Adverse Reactions ( 6.2)] .

Impaired Wound Healing

Because of the inhibitory effect of corticosteroids on wound healing, patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should avoid using fluticasone propionate nasal spray until healing has occurred.

Use of intranasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use fluticasone propionate nasal spray long-term

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, and rash) have been reported after administration of fluticasone propionate nasal spray. Discontinue fluticasone propionate nasal spray if such reactions occur  [see Contraindications ( 4)] . Rarely, immediate hypersensitivity reactions may occur after the administration of fluticasone propionate nasal spray.

Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the complete prescribing information for VZIG and IG.) If chickenpox develops, treatment with antiviral agents may be considered.

Intranasal corticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculous infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

When intranasal corticosteroids are used at higher than recommended dosages or in susceptible individuals at recommended dosages, systemic corticosteroid effects such as hypercorticism and adrenal suppression may appear. If such changes occur, the dosage of fluticasone propionate nasal spray should be discontinued slowly consistent with accepted procedures for discontinuing oral corticosteroid therapy.

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency. In addition, some patients may experience symptoms of corticosteroid withdrawal (e.g., joint and/or muscular pain, lassitude, depression). Patients previously treated for prolonged periods with systemic corticosteroids and transferred to topical corticosteroids should be carefully monitored for acute adrenal insufficiency in response to stress. In patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, rapid decreases in systemic corticosteroid dosages may cause a severe exacerbation of their symptoms.

The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, nefazodone, voriconazole) with fluticasone propionate nasal spray is not recommended because increased systemic corticosteroid adverse effects may occur [see Drug Interactions ( 7.1), Clinical Pharmacology ( 12.3)] .

Intranasal corticosteroids may cause a reduction in growth velocity when administered to pediatric patients [see Use in Specific Populations ( 8.4)] . Monitor the growth routinely of pediatric patients receiving fluticasone propionate nasal spray. To minimize the systemic effects of intranasal corticosteroids, including fluticasone propionate nasal spray, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration ( 2), Use in Specific Populations ( 8.4)] .

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

In controlled US clinical trials, more than 3,300 subjects with allergic and nonallergic rhinitis received treatment with intranasal fluticasone propionate. In general, adverse reactions in clinical trials have been primarily associated with irritation of the nasal mucous membranes, and the adverse reactions were reported with approximately the same frequency by subjects treated with placebo. Less than 2% of subjects in clinical trials discontinued because of adverse reactions; this rate was similar for vehicle placebo and active comparators.

The safety data described below are based on 7 placebo-controlled clinical trials in subjects with allergic rhinitis. The 7 trials included 536 subjects (57 girls and 108 boys aged 4 to 11 years, 137 female and 234 male adolescents and adults) treated with fluticasone propionate nasal spray 200 mcg once daily over 2 to 4 weeks and 2 placebo-controlled clinical trials which included 246 subjects (119 female and 127 male adolescents and adults) treated with fluticasone propionate nasal spray 200 mcg once daily over 6 months (Table 1). Also included in Table 1 are adverse reactions from 2 trials in which 167 children (45 girls and 122 boys aged 4 to 11 years) were treated with fluticasone propionate nasal spray 100 mcg once daily for 2 to 4 weeks.

Table 1. Adverse Reactions with Fluticasone propionate Nasal Spray with >3% Incidence and More Common than Placebo in Subjects≥ 4 Years with Allergic Rhinitis

<div class="scrollingtable"><table border="1" cellpadding="0" cellspacing="0"> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold"><span class="Underline">Adverse Reaction</span></span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fluticasone propionate 100 mcg</span> </p> <p> <span class="Bold">Once Daily</span> </p> <p> <span class="Bold">(n = 167)</span> </p> <p> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Fluticasone propionate 200 mcg</span> </p> <p> <span class="Bold">Once Daily</span> </p> <p> <span class="Bold">(n = 782)</span> </p> <p> <span class="Bold">%</span> </p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First"> <span class="Bold">Placebo</span> </p> <p> <span class="Bold">(n = 758)</span> </p> <p> <span class="Bold">%</span> </p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Headache</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.6</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">16.1</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">14.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Pharyngitis</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.8</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Epistaxis</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">6.9</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">5.4</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Nasal burning/nasal irritation</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.4</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.2</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.6</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Nausea/vomiting</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">4.8</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.6</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2</p> </td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Asthma symptoms</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">7.2</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.3</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.9</p> </td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">Cough</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.6</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">3.8</p> </td><td class="Botrule Lrule Rrule Toprule" valign="top"> <p class="First">2.8</p> </td> </tr> </tbody> </table></div>

Other adverse reactions with fluticasone propionate nasal spray observed with an incidence less than or equal to 3% but greater than or equal to 1% and more common than with placebo included: blood in nasal mucus, runny nose, abdominal pain, diarrhea, fever, flu-like symptoms, aches and pains, dizziness, and bronchitis.

In addition to adverse events reported from clinical trials, the following adverse events have been identified during post approval use of intranasal fluticasone propionate. 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate or a combination of these factors.

General Disorders and Administration Site Conditions

Hypersensitivity reactions, including angioedema, skin rash, edema of the face and tongue, pruritus, urticaria, bronchospasm, wheezing, dyspnea, and anaphylaxis/anaphylactoid reactions, which in rare instances were severe.

Ear and Labyrinth Disorders

Alteration or loss of sense of taste and/or smell and, rarely, nasal septal perforation, nasal ulcer, sore throat, throat irritation and dryness, cough, hoarseness, and voice changes.

Eye Disorders

Dryness and irritation, conjunctivitis, blurred vision, glaucoma, increased intraocular pressure, and cataracts.

Cases of growth suppression have been reported for intranasal corticosteroids, including fluticasone propionate nasal spray  [see Warnings and Precautions ( 5.7)] .

Fluticasone propionate is a substrate of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin, conivaptan, lopinavir, nefazodone, voriconazole) with fluticasone propionate nasal spray is not recommended because increased systemic corticosteroid adverse effects may occur.

Ritonavir

A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations  [see Clinical Pharmacology ( 12.3)].  During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate products, including fluticasone propionate nasal spray, with ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.

Ketoconazole

Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol.

Risk Summary

There are insufficient data on the use of fluticasone propionate nasal spray in pregnant women to inform a drug-associated risk. In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, were observed in rats, mice, and rabbits with subcutaneously administered maternal toxic doses of fluticasone propionate 5 times, equivalent to, and less than the maximum recommended human daily intranasal dose (MRHDID) on a mcg/m 2 basis, respectively. ( See Animal Data.) However, fluticasone propionate administered via nose-only inhalation to rats decreased fetal body weight, but did not induce teratogenicity at a maternal toxic dose equivalent to the MRHDID on a mcg/m 2 basis. ( See Animal Data.) Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans.

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

Data

Human Data: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery.

Animal Data: In embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 5 times the MRHDID of 200 mcg/day (on a mcg/m 2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). The rat no observed adverse effect level (NOAEL) was observed at approximately equivalent to the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately equivalent to the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). The mouse NOAEL was observed with a dose approximately 0.3 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 15 mcg/kg/day).

In an embryofetal development study with pregnant rats dosed by the nose-only inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately equivalent to the MRHDID (on a mcg/m 2 basis with a maternal nose-only inhalation dose of 25.7 mcg/kg/day); however, there was no evidence of teratogenicity. The NOAEL was observed with a dose approximately 0.25 times the MRHDID (on a mcg/m 2 basis with a maternal nose-only inhalation dose of 5.5 mcg/kg/day).

In an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.06 times the MRHDID and higher (on a mcg/m 2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day). Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at a dose 0.39 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). The NOAEL was observed in rabbit fetuses with a dose approximately 0.01 times the MRHDID (on a mcg/m 2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day).

Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.

In a pre- and post-natal development study in pregnant rats dosed from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 2 times the MRHDID (on a mcg/m 2 basis with maternal subcutaneous doses up to 50 mcg/kg/day).

Risk Summary

There are no available data on the presence of fluticasone propionate in human milk, the effects on the breastfed child, or the effects on milk production. Low concentrations of other corticosteroids have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for fluticasone propionate nasal spray and any potential adverse effects on the breastfed child from fluticasone propionate nasal spray or from the underlying maternal condition.

Data

Animal Data:Subcutaneous administration of tritiated fluticasone propionate at a dose of 10 mcg/kg/day to lactating rats resulted in measurable levels in milk.

The safety and effectiveness of fluticasone propionate nasal spray in children aged 4 years and older have been established [ see Adverse Reactions ( 6.1), Clinical Pharmacology ( 12.3) ]. Six hundred fifty (650) subjects aged 4 to 11 years and 440 subjects aged 12 to 17 years were studied in US clinical trials with fluticasone propionate nasal spray. The safety and effectiveness of fluticasone propionate nasal spray in children younger than 4 years have not been established.

Effects on Growth

Controlled clinical trials have shown that intranasal corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. This effect was observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with intranasal corticosteroids, including the impact on final adult height, are unknown. The potential for “catch-up” growth following discontinuation of treatment with intranasal corticosteroids has not been adequately studied. The growth of pediatric patients receiving intranasal corticosteroids, including fluticasone propionate nasal spray, should be monitored routinely (e.g., via stadiometry). The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of intranasal corticosteroids, including fluticasone propionate nasal spray, each patient’s dosage should be titrated to the lowest dosage that effectively controls his/her symptoms.

A 1-year placebo-controlled trial was conducted in 150 pediatric subjects (aged 3 to 9 years) to assess the effect of fluticasone propionate nasal spray (single daily dose of 200 mcg) on growth velocity. From the primary population receiving fluticasone propionate nasal spray (n=56) and placebo (n=52), the point estimate for growth velocity with fluticasone propionate nasal spray was 0.14 cm/year lower than placebo (95% CI:-0.54, 0.27 cm/year). Thus, no statistically significant effect on growth was noted compared with placebo. No evidence of clinically relevant changes in HPA axis function or bone mineral density was observed as assessed by 12-hour urinary cortisol excretion and dual-energy x-ray absorptiometry, respectively.

The potential for fluticasone propionate nasal spray to cause growth suppression in susceptible patients or when given at higher than recommended dosages cannot be ruled out.

A limited number of subjects aged 65 years and older (n=129) or 75 years and older (n=11) have been treated with fluticasone propionate nasal spray in clinical trials. While the number of subjects is too small to permit separate analysis of efficacy and safety, the adverse reactions reported in this population were similar to those reported by younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Formal pharmacokinetic trials using fluticasone propionate nasal spray have not been conducted in subjects with hepatic impairment. Since fluticasone propionate is predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate in plasma. Therefore, patients with hepatic disease should be closely monitored.

Formal pharmacokinetic trials using fluticasone propionate nasal spray have not been conducted in subjects with renal impairment.

Chronic overdosage may result in signs/symptoms of hypercorticism  [see Warnings and Precautions ( 5.5)].  Intranasal administration of 2 mg (10 times the recommended dose) of fluticasone propionate twice daily for 7 days was administered to healthy human volunteers. Adverse events reported with fluticasone propionate were similar to placebo, and no clinically significant abnormalities in laboratory safety tests were observed. Single oral doses up to 16 mg have been studied in human volunteers with no acute toxic effects reported. Repeat oral doses up to 80 mg daily for 10 days in volunteers and repeat oral doses up to 10 mg daily for 14 days in patients were well tolerated. Adverse reactions were of mild or moderate severity, and incidences were similar in active and placebo treatment groups. Acute overdosage with this dosage form is unlikely since one bottle of fluticasone propionate nasal spray contains approximately 8 mg of fluticasone propionate.

{ "type": "p", "children": [], "text": "Chronic overdosage may result in signs/symptoms of hypercorticism \n \n [see Warnings and Precautions (\n \n 5.5)].\n \n  Intranasal administration of 2 mg (10 times the recommended dose) of fluticasone propionate twice daily for 7 days was administered to healthy human volunteers. Adverse events reported with fluticasone propionate were similar to placebo, and no clinically significant abnormalities in laboratory safety tests were observed. Single oral doses up to 16 mg have been studied in human volunteers with no acute toxic effects reported. Repeat oral doses up to 80 mg daily for 10 days in volunteers and repeat oral doses up to 10 mg daily for 14 days in patients were well tolerated. Adverse reactions were of mild or moderate severity, and incidences were similar in active and placebo treatment groups. Acute overdosage with this dosage form is unlikely since one bottle of fluticasone propionate nasal spray contains approximately 8 mg of fluticasone propionate.\n\n " }

The active component of fluticasone propionate nasal spray USP is fluticasone propionate USP, a corticosteroid having the chemical name S-(fluoromethyl)6α,9-difluoro-11β-17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, 17-propionate and the following chemical structure:

{ "type": "p", "children": [], "text": "The active component of fluticasone propionate nasal spray USP is fluticasone propionate USP, a corticosteroid having the chemical name S-(fluoromethyl)6α,9-difluoro-11β-17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, 17-propionate and the following chemical structure:" }

Fluticasone propionate is a white to off-white powder with a molecular weight of 500.6 and the molecular formula is C 25H 31F 3O 5S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol. Fluticasone propionate nasal spray, 50 mcg is an aqueous suspension of microfine fluticasone propionate for topical administration to the nasal mucosa by means of a metering, atomizing spray pump. Fluticasone propionate nasal spray also contains 0.02% w/w benzalkonium chloride, dextrose, microcrystalline cellulose and carboxymethylcellulose sodium, 0.25% w/w phenylethyl alcohol and polysorbate 80 and has a pH between 5 and 7.

{ "type": "p", "children": [], "text": "Fluticasone propionate is a white to off-white powder with a molecular weight of 500.6 and the molecular formula is C\n \n 25H\n \n 31F\n \n 3O\n \n 5S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol. \n Fluticasone propionate nasal spray, 50 mcg is an aqueous suspension of microfine fluticasone propionate for topical administration to the nasal mucosa by means of a metering, atomizing spray pump. Fluticasone propionate nasal spray also contains 0.02% w/w benzalkonium chloride, dextrose, microcrystalline cellulose and carboxymethylcellulose sodium, 0.25% w/w phenylethyl alcohol and polysorbate 80 and has a pH between 5 and 7.\n\n " }

After initial priming, each actuation delivers 50 mcg of fluticasone propionate in 100 mg of formulation through the nasal adapter.

{ "type": "p", "children": [], "text": "\n After initial priming, each actuation delivers 50 mcg of fluticasone propionate in 100 mg of formulation through the nasal adapter.\n " }

Fluticasone propionate is a synthetic, trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone propionate has been shown  in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is 18 times that of dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results. The clinical significance of these findings is unknown.

The precise mechanism through which fluticasone propionate affects rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation. In 7 trials in adults, fluticasone propionate nasal spray has decreased nasal mucosal eosinophils in 66% of patients (35% for placebo) and basophils in 39% of patients (28% for placebo). The direct relationship of these findings to long-term symptom relief is not known.

HPA Axis Effect

The potential systemic effects of fluticasone propionate nasal spray on the HPA axis were evaluated. Fluticasone propionate nasal spray given as 200 mcg once daily or 400 mcg twice daily was compared with placebo or oral prednisone 7.5 or 15 mg given in the morning. Fluticasone propionate nasal spray at either dosage for 4 weeks did not affect the adrenal response to 6-hour cosyntropin stimulation, while both dosages of oral prednisone significantly reduced the response to cosyntropin.

Cardiac Electrophysiology

A study specifically designed to evaluate the effect of fluticasone propionate nasal spray on the QT interval has not been conducted.

The activity of fluticasone propionate nasal spray is due to the parent drug, fluticasone propionate. Due to the low bioavailability by the intranasal route, the majority of the pharmacokinetic data was obtained via other routes of administration.

Absorption

Indirect calculations indicate that fluticasone propionate delivered by the intranasal route has an absolute bioavailability averaging less than 2%. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. After intranasal treatment of patients with rhinitis for 3 weeks, fluticasone propionate plasma concentrations were above the level of detection (50 pg/mL) only when recommended doses were exceeded and then only in occasional samples at low plasma levels.

Distribution

Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 L/kg.

The percentage of fluticasone propionate bound to human plasma proteins averaged 99%. Fluticasone propionate is weakly and reversibly bound to erythrocytes and is not significantly bound to human transcortin.

Elimination

Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. The total blood clearance of fluticasone propionate is high (average: 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total.

Metabolism:The only circulating metabolite detected in man is the 17β-carboxylic acid derivative of fluticasone propionate, which is formed through the CYP3A4 pathway. This metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol  in vitroand negligible pharmacological activity in animal studies. Other metabolites detected  in vitrousing cultured human hepatoma cells have not been detected in man.

Excretion:Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites.

Special Populations

Fluticasone propionate nasal spray was not studied in any special populations, and no gender-specific pharmacokinetic data have been obtained.

Drug Interactions

Inhibitors of Cytochrome P450 3A4: Ritonavir:Fluticasone propionate is a substrate of CYP3A4. Coadministration of fluticasone propionate and the strong CYP3A4 inhibitor, ritonavir, is not recommended based upon a multiple-dose, crossover drug interaction trial in 18 healthy subjects. Fluticasone propionate aqueous nasal spray (200 mcg once daily) was coadministered for 7 days with ritonavir (100 mg twice daily). Plasma fluticasone propionate concentrations following fluticasone propionate aqueous nasal spray alone were undetectable (<10 pg/mL) in most subjects, and when concentrations were detectable, peak levels (C max) averaged 11.9 pg/mL (range: 10.8 to 14.1 pg/mL) and AUC (0-τ)averaged 8.43 pg•h/mL (range: 4.2 to 18.8 pg•h/mL). Fluticasone propionate C maxand AUC (0-τincreased to 318 pg/mL (range: 110 to 648 pg/mL) and 3,102.6 pg•h/mL (range: 1,207.1 to 5,662.0 pg•h/mL), respectively, after coadministration of ritonavir with fluticasone propionate aqueous nasal spray. This significant increase in plasma fluticasone propionate exposure resulted in a significant decrease (86%) in serum cortisol AUC.

Ketoconazole:Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol AUC, but had no effect on urinary excretion of cortisol.

Erythromycin:In a multiple-dose drug interaction study, coadministration of orally inhaled fluticasone propionate (500 mcg twice daily) and erythromycin (333 mg 3 times daily) did not affect fluticasone propionate pharmacokinetics.

Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 25 and 20 times the MRHDID in adults and children, respectively, on a mcg/m 2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 3 and 2 times the MRHDID in adults and children, respectively, on a mcg/m 2 basis) for 104 weeks.

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells  in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes  in vitro or in the mouse micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 2 times the MRHDID in adults on a mcg/m 2 basis).

Perennial Nonallergic Rhinitis

{ "type": "p", "children": [], "text": "\nPerennial Nonallergic Rhinitis\n" }

Three randomized, double-blind, parallel-group, vehicle placebo-controlled trials were conducted in 1,191 subjects to investigate regular use of fluticasone propionate nasal spray in subjects with perennial nonallergic rhinitis. These trials evaluated subject-rated total nasal symptom scores (TNSS) that included nasal obstruction, postnasal drip, rhinorrhea in subjects treated for 28 days of double-blind therapy and in 1 of the 3 trials for 6 months of open-label treatment. Two of these trials demonstrated that subjects treated with fluticasone propionate nasal spray (100 mcg twice daily) exhibited statistically significant decreases in TNSS compared with subjects treated with vehicle.

{ "type": "p", "children": [], "text": "Three randomized, double-blind, parallel-group, vehicle placebo-controlled trials were conducted in 1,191 subjects to investigate regular use of fluticasone propionate nasal spray in subjects with perennial nonallergic rhinitis. These trials evaluated subject-rated total nasal symptom scores (TNSS) that included nasal obstruction, postnasal drip, rhinorrhea in subjects treated for 28 days of double-blind therapy and in 1 of the 3 trials for 6 months of open-label treatment. Two of these trials demonstrated that subjects treated with fluticasone propionate nasal spray (100 mcg twice daily) exhibited statistically significant decreases in TNSS compared with subjects treated with vehicle." }

Fluticasone Propionate Nasal Spray USP, 50 mcg is supplied in an amber glass bottle fitted with a white metering atomizing pump, white nasal adapter fitted with a clear plastic dust cap, in a box of one (NDC 72888-141-35) with FDA-approved Patient Labeling (see Patient Instructions for Use for proper actuation of the device). Each bottle contains a net fill weight of 16 g and will provide 120 actuations. Each actuation delivers 50 mcg of fluticasone propionate in 100 mg of formulation through the nasal adapter. The correct amount of medication in each spray cannot be assured after 120 sprays even though the bottle is not completely empty. The bottle should be discarded when the labeled number of actuations has been used.

{ "type": "p", "children": [], "text": "Fluticasone Propionate Nasal Spray USP, 50 mcg is supplied in an amber glass bottle fitted with a white metering atomizing pump, white nasal adapter fitted with a clear plastic dust cap, in a box of one (NDC 72888-141-35) with FDA-approved Patient Labeling (see Patient Instructions for Use for proper actuation of the device). Each bottle contains a net fill weight of 16 g and will provide 120 actuations. Each actuation delivers 50 mcg of fluticasone propionate in 100 mg of formulation through the nasal adapter. The correct amount of medication in each spray cannot be assured after 120 sprays even though the bottle is not completely empty. The bottle should be discarded when the labeled number of actuations has been used." }

Store between 4° and 30°C (39° and 86°F).

{ "type": "p", "children": [], "text": "\nStore between 4° and 30°C (39° and 86°F).\n" }

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).\n" }

Local Nasal Effects

{ "type": "p", "children": [], "text": "\nLocal Nasal Effects\n" }

Inform patients that treatment with fluticasone propionate nasal spray may lead to adverse reactions, which include epistaxis and nasal ulceration.  Candida infection may also occur with treatment with fluticasone propionate nasal spray. In addition, fluticasone propionate nasal spray has been associated with nasal septal perforation and impaired wound healing. Patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use fluticasone propionate nasal spray until healing has occurred  [see Warnings and Precautions ( 5.1)] .

{ "type": "p", "children": [], "text": "Inform patients that treatment with fluticasone propionate nasal spray may lead to adverse reactions, which include epistaxis and nasal ulceration. \n \n Candida infection may also occur with treatment with fluticasone propionate nasal spray. In addition, fluticasone propionate nasal spray has been associated with nasal septal perforation and impaired wound healing. Patients who have experienced recent nasal ulcers, nasal surgery, or nasal trauma should not use fluticasone propionate nasal spray until healing has occurred \n \n [see Warnings and Precautions (\n \n 5.1)]\n \n .\n\n " }

Glaucoma and Cataracts

{ "type": "p", "children": [], "text": "\nGlaucoma and Cataracts\n" }

Inform patients that glaucoma and cataracts are associated with nasal and inhaled corticosteroid use. Advise patients to notify their healthcare providers if a change in vision is noted while using fluticasone propionate nasal spray  [see Warnings and Precautions ( 5.2)] .

{ "type": "p", "children": [], "text": "Inform patients that glaucoma and cataracts are associated with nasal and inhaled corticosteroid use. Advise patients to notify their healthcare providers if a change in vision is noted while using fluticasone propionate nasal spray \n \n [see Warnings and Precautions (\n \n 5.2)]\n \n .\n\n " }

Hypersensitivity Reactions, including Anaphylaxis

{ "type": "p", "children": [], "text": "\nHypersensitivity Reactions, including Anaphylaxis\n" }

Inform patients that hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, contact dermatitis, and rash, may occur after administration of fluticasone propionate nasal spray. If such reactions occur, patients should discontinue use of fluticasone propionate nasal spray  [see Warnings and Precautions ( 5.3)].

{ "type": "p", "children": [], "text": "Inform patients that hypersensitivity reactions, including anaphylaxis, angioedema, urticaria, contact dermatitis, and rash, may occur after administration of fluticasone propionate nasal spray. If such reactions occur, patients should discontinue use of fluticasone propionate nasal spray \n \n [see Warnings and Precautions (\n \n 5.3)].\n \n \n" }

Immunosuppression

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

Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and if they are exposed to consult their healthcare provider without delay. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex  [see Warnings and Precautions ( 5.4)] .

{ "type": "p", "children": [], "text": "Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and if they are exposed to consult their healthcare provider without delay. Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex \n \n [see Warnings and Precautions (\n \n 5.4)]\n \n .\n\n " }

Reduced Growth Velocity

{ "type": "p", "children": [], "text": "\nReduced Growth Velocity\n" }

Advise parents that fluticasone propionate nasal spray may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route  [see Warnings and Precautions ( 5.7), Pediatric Use ( 8.4)] .

{ "type": "p", "children": [], "text": "Advise parents that fluticasone propionate nasal spray may cause a reduction in growth velocity when administered to pediatric patients. Physicians should closely follow the growth of children and adolescents taking corticosteroids by any route \n \n [see Warnings and Precautions (\n \n 5.7), Pediatric Use (\n \n 8.4)]\n \n .\n\n " }

Use Daily for Best Effect

{ "type": "p", "children": [], "text": "\nUse Daily for Best Effect\n" }

Inform patients that they should use fluticasone propionate nasal spray on a regular basis. Fluticasone propionate nasal spray, like other corticosteroids, does not have an immediate effect on rhinitis symptoms. Maximum benefit may not be reached for several days. Patients should not increase the prescribed dosage but should contact their healthcare providers if symptoms do not improve or if the condition worsens.

{ "type": "p", "children": [], "text": "Inform patients that they should use fluticasone propionate nasal spray on a regular basis. Fluticasone propionate nasal spray, like other corticosteroids, does not have an immediate effect on rhinitis symptoms. Maximum benefit may not be reached for several days. Patients should not increase the prescribed dosage but should contact their healthcare providers if symptoms do not improve or if the condition worsens." }

Keep Spray Out of Eyes and Mouth

{ "type": "p", "children": [], "text": "\nKeep Spray Out of Eyes and Mouth\n" }

Inform patients to avoid spraying fluticasone propionate nasal spray in their eyes and mouth.

{ "type": "p", "children": [], "text": "Inform patients to avoid spraying fluticasone propionate nasal spray in their eyes and mouth." }

Distributed by: Advagen Pharma Ltd., East Windsor, NJ 08520, USA

{ "type": "p", "children": [], "text": "\nDistributed by:\n Advagen Pharma Ltd., \n East Windsor, NJ 08520, USA\n\n " }

Rev. 06/2025

{ "type": "p", "children": [], "text": "Rev. 06/2025" }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <tbody class="Headless"> <tr> <td align="center" valign="top"><span class="Bold">Patient Information <br/> Fluticasone Propionate (floo tik’ a sone proe’ pee oh nate) </span> <br/> <span class="Bold">Nasal Spray USP, 50 mcg</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" valign=\"top\"><span class=\"Bold\">Patient Information \n <br/> Fluticasone Propionate (floo tik’ a sone proe’ pee oh nate)\n </span>\n<br/>\n<span class=\"Bold\">Nasal Spray USP, 50 mcg</span></td>\n</tr>\n</tbody>\n</table></div>" }

What isfluticasone propionatenasal spray?

{ "type": "p", "children": [], "text": "\nWhat isfluticasone propionatenasal spray?\n" }

Fluticasone propionate nasal spray is a prescription medicine used to treat non-allergy nasal symptoms such as runny nose, stuffy nose, sneezing, and nasal itching in adults and children aged 4 years and older.

{ "type": "p", "children": [], "text": "Fluticasone propionate nasal spray is a prescription medicine used to treat non-allergy nasal symptoms such as runny nose, stuffy nose, sneezing, and nasal itching in adults and children aged 4 years and older." }

It is not known if fluticasone propionate nasal spray is safe and effective in children younger than 4 years of age.

{ "type": "p", "children": [], "text": "It is not known if fluticasone propionate nasal spray is safe and effective in children younger than 4 years of age." }

Do not usefluticasone propionatenasal sprayif you are allergic to fluticasone propionate or any of the ingredients in fluticasone propionate nasal spray. See “What are the ingredients in fluticasone propionate nasal spray?” below for a complete list of ingredients.

{ "type": "p", "children": [], "text": "\nDo not usefluticasone propionatenasal sprayif you are allergic to fluticasone propionate or any of the ingredients in fluticasone propionate nasal spray. See “What are the ingredients in fluticasone propionate nasal spray?” below for a complete list of ingredients.\n\n " }

Before usingfluticasone propionatenasal spray, tell your healthcare provider about all of your medical conditions, including if you:

{ "type": "p", "children": [], "text": "\nBefore usingfluticasone propionatenasal spray, tell your healthcare provider about all of your medical conditions, including if you:\n" }

{ "type": "ul", "children": [ "have or have had nasal sores, nasal surgery, or nasal injury.", "have or have had eye problems, such as glaucoma or cataracts.", "have an immune system problem.", "have any type of viral, bacterial, or fungal infection.", "are exposed to chickenpox or measles.", "are pregnant or planning to become pregnant. It is not known if fluticasone propionate nasal spray may harm your unborn baby.", "are breastfeeding or plan to breastfeed. It is not known if fluticasone passes into your breast milk and if it can harm your baby." ], "text": "" }

Tell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins, and herbal supplements. Fluticasone propionate nasal spray and certain other medicines may interact with each other. This may cause serious side effects.

{ "type": "p", "children": [], "text": "Tell your healthcare provider about all the medicines you take,including prescription and over-the-counter medicines, vitamins, and herbal supplements. Fluticasone propionate nasal spray and certain other medicines may interact with each other. This may cause serious side effects." }

Especially, tell your healthcare provider if you take antifungal or anti-HIV medicines.

{ "type": "p", "children": [], "text": "\nEspecially, tell your healthcare provider if you take antifungal or anti-HIV medicines.\n" }

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

{ "type": "p", "children": [], "text": "Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine." }

How should I usefluticasone propionatenasal spray?

{ "type": "p", "children": [], "text": "\nHow should I usefluticasone propionatenasal spray?\n" }

{ "type": "ul", "children": [ "\nRead the step-by-step instructions for usingfluticasone propionatenasal spray at the end of this Patient Information.\n", "Fluticasone propionate nasal spray is for use in your nose only. Do not spray it in your eyes or mouth.", "Children should use fluticasone propionate nasal spray with an adult’s help, as instructed by the child’s healthcare provider.", "Use fluticasone propionate nasal spray exactly as your healthcare provider tells you. Do not use fluticasone propionate nasal spray more often than prescribed.", "Fluticasone propionate nasal spray may take several days of regular use for your rhinitis symptoms to get better. If your symptoms do not improve or get worse, call your healthcare provider.", "You will get the best results if you keep using fluticasone propionate nasal spray regularly each day without missing a dose. After you begin to feel better, your healthcare provider may decrease your dose.\n \n Do notstop using fluticasone propionate nasal spray unless your healthcare provider tells you to do so.\n \n " ], "text": "" }

What are the possible side effects offluticasone propionatenasal spray?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects offluticasone propionatenasal spray?\n" }

Fluticasone propionatenasal spray may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nFluticasone propionatenasal spray may cause serious side effects, including:\n" }

{ "type": "ul", "children": [ "\nnose problems.Nose problems may include:\n \n \n\nnose bleeds.\n\n\nsores (ulcers) in your nose.\n\n\na certain fungal infection in your nose, mouth, or throat (thrush).\n\n\nhole in the cartilage of your nose (nasal septal perforation).\n\n\n" ], "text": "" }

Symptoms of nasal septal perforation may include:

{ "type": "p", "children": [], "text": "Symptoms of nasal septal perforation may include:" }

{ "type": "ul", "children": [ "\n\ncrusting in the nose\nnose bleeds\nrunny nose\nwhistling sound when you breathe\n\nslow wound healing.You should not use fluticasone propionate nasal spray until your nose has healed if you have a sore in your nose, have had surgery on your nose, or if your nose has been injured.\n \n \n\n", "\nglaucoma and cataracts. Using nasal and inhaled corticosteroid medicines may result in you developing glaucoma and/or cataracts. Your healthcare provider may have you see an eye doctor (ophthalmologist) if you develop eye symptoms or use fluticasone propionate nasal spray for long periods of time. Tell your healthcare provider if you have any changes in your eye sight while using fluticasone propionate nasal spray.\n \n ", "\nserious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following signs of a serious allergic reaction:\n \n \nrash\nhives\nswelling of your face, mouth, and tongue\nbreathing problems\n\n", "\nweakened immune system and increased chance of getting infections (immunosuppression). Taking medicines that weaken your immune system makes you more likely to get infections and can make certain infections worse. These infections may include tuberculosis (TB), ocular herpes simplex infections, and infections caused by fungi, bacteria, viruses, and parasites. Avoid contact with people who have a contagious disease such as chickenpox or measles while using fluticasone propionate nasal spray. If you come in contact with someone who has chickenpox or measles call your healthcare provider right away. Symptoms of an infection may include:\n \n \nfever\nfeeling\ntired\npain\nnausea\naches\nvomiting\nchills\n\n", "\nlowered steroid hormone levels (adrenal insufficiency).Adrenal insufficiency happens when your adrenal glands do not make enough steroid hormones. This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking medicine containing an inhaled steroid (such as fluticasone propionate nasal spray). Symptoms of adrenal insufficiency may include:\n \n \nfeeling tired\nlack of energy\nweakness\nnausea and vomiting\nlow blood pressure\n\n", "\nslowed growth in children. A child’s growth should be checked often. \n \nThe most common side effects of fluticasone propionate nasal spray include:\n", "headache", "nausea and vomiting", "sore throat", "trouble breathing", "nose bleeds", "cough", "nose burning or itching" ], "text": "" }

These are not all the possible side effects with fluticasone propionate nasal spray.

{ "type": "p", "children": [], "text": "These are not all the possible side effects with fluticasone propionate nasal spray." }

Call your doctor for medical advice about side effects. You may report side effects to FDA at

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects. You may report side effects to FDA at" }

1-800-FDA-1088.

{ "type": "p", "children": [], "text": "1-800-FDA-1088." }

How do I storeFluticasone Propionate Nasal Spray?

{ "type": "p", "children": [], "text": "\nHow do I storeFluticasone Propionate Nasal Spray?\n" }

{ "type": "ul", "children": [ "Store fluticasone propionate nasal spray between 39° and 86°F (4° and 30°C)." ], "text": "" }

Keepfluticasone propionate nasal spray and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeepfluticasone propionate nasal spray and all medicines out of the reach of children.\n" }

General information about the safe and effective use offluticasone propionate nasal spray.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use offluticasone propionate nasal spray.\n" }

Medicines are sometimes prescribed for purposes not mentioned in a Patient Information leaflet. Do not use fluticasone propionate nasal spray for a condition for which it was not prescribed. Do not give your fluticasone propionate nasal spray to other people, even if they have the same condition that you have. It may harm them.

{ "type": "p", "children": [], "text": "Medicines are sometimes prescribed for purposes not mentioned in a Patient Information leaflet. Do not use fluticasone propionate nasal spray for a condition for which it was not prescribed. Do not give your fluticasone propionate nasal spray to other people, even if they have the same condition that you have. It may harm them." }

You can ask your pharmacist or healthcare provider for information about fluticasone propionate nasal spray that was written for healthcare professionals.

{ "type": "p", "children": [], "text": "You can ask your pharmacist or healthcare provider for information about fluticasone propionate nasal spray that was written for healthcare professionals." }

What are the ingredients influticasone propionate nasal spray USP?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients influticasone propionate nasal spray USP?\n" }

Active ingredient:fluticasone propionate USP.

{ "type": "p", "children": [], "text": "\nActive ingredient:fluticasone propionate USP.\n\n " }

Inactive ingredients:0.02% w/w benzalkonium chloride, dextrose, microcrystalline cellulose and carboxymethylcellulose sodium, 0.25% w/w phenylethyl alcohol and polysorbate 80.

{ "type": "p", "children": [], "text": "\nInactive ingredients:0.02% w/w benzalkonium chloride, dextrose, microcrystalline cellulose and carboxymethylcellulose sodium, 0.25% w/w phenylethyl alcohol and polysorbate 80.\n\n " }

For more information about fluticasone propionate nasal spray, call 866-488-0312.

{ "type": "p", "children": [], "text": "For more information about fluticasone propionate nasal spray, call 866-488-0312." }

Distributed by: Advagen Pharma Limited, East Windsor, NJ 08520, USA Rev 11/2024

{ "type": "p", "children": [], "text": "\nDistributed by:\n Advagen Pharma Limited, \n East Windsor, NJ 08520, USA \n \n Rev 11/2024\n\n " }

<div class="scrollingtable"><table class="Noautorules" width="100%"> <tbody class="Headless"> <tr> <td align="center" valign="top"> <p class="First"> <span class="Bold">Instruction for Use</span> </p> <span class="Bold">Fluticasone Propionate</span><span class="Bold">(flootik’ a sone proe’ pee oh nate)</span> <br/> <span class="Bold">Nasal Spray USP, 50 mcg</span></td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"100%\">\n<tbody class=\"Headless\">\n<tr>\n<td align=\"center\" valign=\"top\">\n<p class=\"First\">\n<span class=\"Bold\">Instruction for Use</span>\n</p>\n<span class=\"Bold\">Fluticasone Propionate</span><span class=\"Bold\">(flootik’ a sone proe’ pee oh nate)</span>\n<br/>\n<span class=\"Bold\">Nasal Spray USP, 50 mcg</span></td>\n</tr>\n</tbody>\n</table></div>" }

Fluticasone propionatenasal spray is for use in your nose only.

{ "type": "p", "children": [], "text": "\nFluticasone propionatenasal spray is for use in your nose only.\n" }

Read this information before you start using yourfluticasone propionatenasal spray.

{ "type": "p", "children": [], "text": "\nRead this information before you start using yourfluticasone propionatenasal spray.\n" }

Parts of yourFluticasone PropionateNasal Spray USP, 50 mcg(See Figure 1)

{ "type": "p", "children": [], "text": "\nParts of yourFluticasone PropionateNasal Spray USP, 50 mcg(See Figure 1)\n\n " }

                                                Figure 1

{ "type": "p", "children": [], "text": "                                                Figure 1" }

Yourfluticasone propionatenasal spray must be primed before you use it for the first time and when you have not used it for a week or more.

{ "type": "p", "children": [], "text": "\nYourfluticasone propionatenasal spray must be primed before you use it for the first time and when you have not used it for a week or more.\n" }

How to prime yourfluticasone propionatenasal spray:

{ "type": "p", "children": [], "text": "\nHow to prime yourfluticasone propionatenasal spray:\n" }

{ "type": "ul", "children": [ "Shake the bottle gently and then remove the dust cap (Figure 2)." ], "text": "" }

                                               Figure 2

{ "type": "p", "children": [], "text": "                                               Figure 2" }

{ "type": "ul", "children": [ "Hold the bottle as shown (Figure 3) with the nasal applicator pointing away from you and with your forefinger and middle finger on either side of the nasal applicator and your thumb underneath the bottle.", "Press down and release\n \n 6times until a fine spray appears (Figure 3). The pump is now ready for use.\n \n " ], "text": "" }

                                               Figure 3

{ "type": "p", "children": [], "text": "                                               Figure 3" }

Using your fluticasone propionate nasal spray:

{ "type": "p", "children": [], "text": "\nUsing your fluticasone propionate nasal spray:\n" }

Step 1:Blow your nose to clear your nostrils.

{ "type": "p", "children": [], "text": "\nStep 1:Blow your nose to clear your nostrils.\n\n " }

Step 2:Close 1nostril. Tilt your head forward slightly and, keeping the bottle upright, carefully insert the nasal applicator into the other nostril (Figure 4).

{ "type": "p", "children": [], "text": "\nStep 2:Close\n \n 1nostril. Tilt your head forward slightly and, keeping the bottle upright, carefully insert the nasal applicator into the other nostril (Figure 4).\n\n " }

                                               Figure 4

{ "type": "p", "children": [], "text": "                                               Figure 4" }

Step 3:Start to breathe in through your nose, and while breathing in press firmly and quickly down 1time on the applicator to release the spray. To get a full dose, use your forefinger and middle finger to spray while supporting the base of the bottle with your thumb. Avoid spraying in eyes. Breathe in gently through the nostril (Figure 5).

{ "type": "p", "children": [], "text": "\nStep 3:Start to breathe in through your nose, and while breathing in press firmly and quickly down\n \n 1time on the applicator to release the spray. To get a full dose, use your forefinger and middle finger to spray while supporting the base of the bottle with your thumb. Avoid spraying in eyes. Breathe in gently through the nostril (Figure 5).\n\n " }

                                               Figure 5

{ "type": "p", "children": [], "text": "                                               Figure 5" }

Step 4:Breathe out through your mouth.

{ "type": "p", "children": [], "text": "\nStep 4:Breathe out through your mouth.\n\n " }

Step 5:If a second spray is required in that nostril, repeat steps 2through 4.

{ "type": "p", "children": [], "text": "\nStep 5:If a second spray is required in that nostril, repeat steps\n \n 2through\n \n 4.\n\n " }

Step 6:Repeat steps 2through 5in the other nostril.

{ "type": "p", "children": [], "text": "\nStep 6:Repeat steps\n \n 2through\n \n 5in the other nostril.\n\n " }

Step 7:Wipe the nasal applicator with a clean tissue and replace the dust cap (Figure 6).

{ "type": "p", "children": [], "text": "\nStep 7:Wipe the nasal applicator with a clean tissue and replace the dust cap (Figure 6).\n\n " }

                                               Figure 6

{ "type": "p", "children": [], "text": "                                               Figure 6" }

Do not use this bottle for more than the labeled number of sprays even though the bottle is not completely empty. Before you throw the bottle away, you should talk to your healthcare provider to see if a refill is needed. Do not take extra doses or stop taking fluticasone propionate nasal spray without talking to your healthcare provider.

{ "type": "p", "children": [], "text": "Do not use this bottle for more than the labeled number of sprays even though the bottle is not completely empty. Before you throw the bottle away, you should talk to your healthcare provider to see if a refill is needed. Do not take extra doses or stop taking fluticasone propionate nasal spray without talking to your healthcare provider." }

Cleaning your fluticasone propionate nasal spray:

{ "type": "p", "children": [], "text": "\nCleaning your fluticasone propionate nasal spray:\n" }

Your nasal spray should be cleaned at least 1time each week.

{ "type": "p", "children": [], "text": "Your nasal spray should be cleaned at least\n \n 1time each week.\n\n " }

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

Storing your fluticasone propionate nasal spray:

{ "type": "p", "children": [], "text": "\nStoring your fluticasone propionate nasal spray:\n" }

{ "type": "ul", "children": [ "Store fluticasone propionate nasal spray between 39° and 86°F (4° and 30°C).", "Do not use your fluticasone propionate nasal spray after the date shown as “EXP” on the label or box." ], "text": "" }

All trademarks are the property of their respective owners.

{ "type": "p", "children": [], "text": "All trademarks are the property of their respective owners." }

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

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

Distributed by: Advagen Pharma Ltd., East Windsor, NJ 08520, USA. Rev. 11/2024

{ "type": "p", "children": [], "text": "\nDistributed by:\n Advagen Pharma Ltd., \n East Windsor, NJ 08520, USA. \n \n Rev. 11/2024\n\n " }

Fluticasone Propionate Nasal Spray USP - 50 mcg 120 Metered Sprays- NDC 72888-141-35 - Bottle's Label

{ "type": "p", "children": [], "text": "\nFluticasone Propionate Nasal Spray USP - 50 mcg 120 Metered Sprays- NDC 72888-141-35 - Bottle's Label\n" }

Fluticasone Propionate Nasal Spray USP - 50 mcg 120 Metered Sprays- NDC 72888-141-35 - Carton's Label

{ "type": "p", "children": [], "text": "\nFluticasone Propionate Nasal Spray USP - 50 mcg 120 Metered Sprays- NDC 72888-141-35 - Carton's Label\n" }

Fluticasone propionate ointment is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adult patients.

{ "type": "p", "children": [], "text": "Fluticasone propionate ointment is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adult patients." }

Apply a thin film of fluticasone propionate ointment to the affected skin areas twice daily. Rub in gently.

{ "type": "p", "children": [], "text": "Apply a thin film of fluticasone propionate ointment to the affected skin areas twice daily. Rub in gently." }

Avoid use with occlusive dressing.

{ "type": "p", "children": [], "text": "Avoid use with occlusive dressing." }

Fluticasone propionate ointment is for topical use only; it is not for ophthalmic, oral or intravaginal use.

{ "type": "p", "children": [], "text": "Fluticasone propionate ointment is for topical use only; it is not for ophthalmic, oral or intravaginal use." }

Ointment, 0.005%. Each gram of Fluticasone Propionate Ointment USP, 0.005% contains 0.05 mg fluticasone propionate in a white to off-white translucent ointment base. Fluticasone propionate ointment is supplied in 5 g physician samples, 15 g, 30 g and 60 g tubes.

{ "type": "p", "children": [], "text": "Ointment, 0.005%. Each gram of Fluticasone Propionate Ointment USP, 0.005% contains 0.05 mg fluticasone propionate in a white to off-white translucent ointment base. Fluticasone propionate ointment is supplied in 5 g physician samples, 15 g, 30 g and 60 g tubes." }

Fluticasone propionate ointment is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation.

{ "type": "p", "children": [], "text": "Fluticasone propionate ointment is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation." }

Topical corticosteroids, including fluticasone propionate ointment, can produce reversible HPA axis suppression with the potential for clinical glucocorticoid insufficiency. Factors that predispose to HPA axis suppression include large treatment surface areas, prolonged use, use under occlusion, altered skin barrier, liver failure, and young age. Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.

If HPA axis suppression is suspected, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. An ACTH stimulation test may be helpful in evaluating patients for HPA axis suppression.

Pediatric patients may be at greater risk of HPA axis suppression due to their higher skin surface area to body mass ratios [ see Use in Specific Populations (8.4)].

HPA axis suppression may occur during or after withdrawal of treatment. If HPA axis suppression is suspected, gradually withdraw the drug, reduce the frequency of application, or substitute with a less potent corticosteroid. Evaluation of HPA axis suppression may be done by using the cosyntropin stimulation test.

Fluticasone propionate ointment may cause local adverse reactions, including skin atrophy [ see Adverse Reactions (6.1, 6.2)]. The risk is greater with use under occlusion.

Allergic contact dermatitis with topical corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation. Such an observation can be corroborated with appropriate diagnostic patch testing. Discontinue fluticasone propionate ointment if appropriate.

If concomitant skin infections are present or develop, use an appropriate antimicrobial. If a favorable response does not occur promptly, discontinue use of fluticasone propionate ointment until the infection has been adequately controlled.

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.

In controlled clinical trials, the total incidence of adverse reactions associated with the use of fluticasone propionate ointment was approximately 4%. These adverse reactions were usually mild, self-limiting, and consisted primarily of pruritus, burning, hypertrichosis, increased erythema, urticaria, irritation, and lightheadedness. Each of these events occurred individually in less than 1% of patients.

The following local adverse reactions have been identified during post-approval use of fluticasone propionate ointment: acneiform dermatitis, edema, rash, hypoaesthesia, pustular psoriasis, skin atrophy.

The following systemic adverse reactions have been identified during post-approval use of fluticasone propionate cream and fluticasone propionate ointment: immunosuppression/ Pneumocystis jiroveciipneumonia/leukopenia/thrombocytopenia; hyperglycemia/glycosuria; Cushing syndrome; generalized body edema/blurred vision; and acute urticarial reaction (edema, urticaria, pruritus, and throat swelling).

The following local adverse reactions have also been reported with the use of topical corticosteroids: telangiectasia, striae, dryness, folliculitis, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria.

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.

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Therefore, fluticasone propionate ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Systemic embryofetal development studies were conducted in mice, rats and rabbits.

Subcutaneous doses of 15 μg/kg/day, 45 μg/kg/day and 150 μg/kg/day of fluticasone propionate were administered to pregnant female mice from gestation days 6 to 15. A teratogenic effect characteristic of corticosteroids (cleft palate) was noted after administration of 45 μg/kg/day and 150 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 15 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Subcutaneous doses of 10 μg/kg/day, 30 μg/kg/day and 100 μg/kg/day of fluticasone propionate were administered to pregnant female rats in two embryofetal development studies (one study administered fluticasone propionate from gestation days 6 to 15 and the other study from gestation days 7 to 17). In the presence of maternal toxicity, fetal effects noted at 100 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) included decreased fetal weights, omphalocele, cleft palate, and retarded skeletal ossification. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 10 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Subcutaneous doses of 0.08 μg/kg/day, 0.57 μg/kg/day and 4 μg/kg/day of fluticasone propionate were administered to pregnant female rabbits from gestation days 6 to 18. Fetal effects noted at 4 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) included decreased fetal weights, cleft palate and retarded skeletal ossification. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 0.57 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Oral doses of 3 μg/kg/day, 30 μg/kg/day and 300 μg/kg/day fluticasone propionate were administered to pregnant female rabbits from gestation days 8 to 20. No fetal or teratogenic effects were noted at oral doses up to 300 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study. However, no fluticasone propionate was detected in the plasma in this study, consistent with the established low bioavailability following oral administration.

Fluticasone propionate crossed the placenta following administration of a subcutaneous or an oral dose of 100 μg/kg tritiated fluticasone propionate to pregnant rats.

Systemically administered corticosteroids appear in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when fluticasone propionate ointment is administered to a nursing woman.

The safety and effectiveness of fluticasone propionate ointment have not been established in pediatric patients. Use of fluticasone propionate ointment in pediatric patients is not recommended.

Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of systemic effects when treated with topical drugs. They are, therefore, also at greater risk of HPA axis suppression and adrenal insufficiency upon the use of topical corticosteroids [ see Warnings and Precautions (5.1)].

In a trial of 35 pediatric subjects treated with fluticasone propionate ointment, 0.005% for atopic dermatitis over at least 35% of body surface area, subnormal adrenal function was observed with cosyntropin stimulation testing at the end of 3 to 4 weeks of treatment in 4 subjects who had normal testing prior to treatment. It is not known if these subjects had recovery of adrenal function because follow-up testing was not performed. The decreased responsiveness of cosyntropin testing was not correlated to age of subject, amount of fluticasone propionate ointment used, or serum levels of fluticasone propionate.

In the above trial, telangiectasia on the face was noted in one subject on the eighth day of a 4-week treatment period. Facial use was discontinued and the telangiectasia resolved.

HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids.

A limited number of patients above 65 years of age (n = 203) have been treated with futicasone propionate ointment in US and non-US clinical trials. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. However, greater sensitivity of some older individuals cannot be ruled out.

Fluticasone Propionate Ointment USP, 0.005% contains fluticasone propionate [ S-Fluoromethyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate], a synthetic fluorinated corticosteroid, for topical use.

{ "type": "p", "children": [], "text": "Fluticasone Propionate Ointment USP, 0.005% contains fluticasone propionate [\n \n S-Fluoromethyl 6α, 9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate], a synthetic fluorinated corticosteroid, for topical use.\n\n " }

Chemically, fluticasone propionate is C 25H 31F 3O 5S. It has the following structural formula:

{ "type": "p", "children": [], "text": "Chemically, fluticasone propionate is C\n \n 25H\n \n 31F\n \n 3O\n \n 5S. It has the following structural formula:\n\n " }

Fluticasone propionate has a molecular weight of 500.6. It is a white to off-white powder and is insoluble in water.

{ "type": "p", "children": [], "text": "Fluticasone propionate has a molecular weight of 500.6. It is a white to off-white powder and is insoluble in water." }

Each gram of Fluticasone Propionate Ointment USP, 0.005% contains fluticasone propionate 0.05 mg in a white to off-white translucent ointment base of microcrystalline wax, mineral oil, propylene glycol and sorbitan sesquioleate.

{ "type": "p", "children": [], "text": "Each gram of Fluticasone Propionate Ointment USP, 0.005% contains fluticasone propionate 0.05 mg in a white to off-white translucent ointment base of microcrystalline wax, mineral oil, propylene glycol and sorbitan sesquioleate." }

Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of fluticasone propionate ointment in corticosteroid-responsive dermatoses is unknown.

Vasoconstrictor Assay

Studies performed with fluticasone propionate ointment indicate that it is in the medium range of potency as demonstrated in vasoconstrictor trials in healthy subjects when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

Absorption

The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle and the integrity of the epidermal barrier. Occlusive dressing enhances penetration. Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption.

In a study of 6 healthy subjects applying 25 g of fluticasone propionate ointment 0.005% twice daily to the trunk and legs for up to 5 days under occlusion, plasma levels of fluticasone ranged from 0.08 to 0.22 ng/mL.

Distribution

The percentage of fluticasone propionate bound to human plasma proteins averaged 91%. Fluticasone propionate is weakly and reversibly bound to erythrocytes. Fluticasone propionate is not significantly bound to human transcortin.

Metabolism

No metabolites of fluticasone propionate were detected in an in vitrostudy of radiolabeled fluticasone propionate incubated in human skin homogenate.

Fluticasone propionate is metabolized in the liver by cytochrome P450 3A4-mediated hydrolysis of the 5-fluoromethyl carbothioate grouping. This transformation occurs in 1 metabolic step to produce the inactive 17-β-carboxylic acid metabolite, the only known metabolite detected in man. This metabolite has approximately 2,000 times less affinity than the parent drug for the glucocorticoid receptor of human lung cytosol in vitroand negligible pharmacological activity in animal studies. Other metabolites detected in vitrousing cultured human hepatoma cells have not been detected in man.

In an oral (gavage) mouse carcinogenicity study, doses of 0.1 mg/kg/day, 0.3 mg/kg/day and 1 mg/kg/day fluticasone propionate were administered to mice for 18 months. Fluticasone propionate demonstrated no tumorigenic potential at oral doses up to 1 mg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study.

In a dermal mouse carcinogenicity study, 0.05% fluticasone propionate ointment (40 μl) was topically administered for 1, 3 or 7 days/week for 80 weeks. Fluticasone propionate demonstrated no tumorigenic potential at dermal doses up to 6.7 μg/kg/day (less than the MRHD in adults based on body surface area comparisons) in this study.

Fluticasone propionate revealed no evidence of mutagenic or clastogenic potential based on the results of five in vitrogenotoxicity tests (Ames assay, E. coli fluctuation test, S. cerevisiae gene conversion test, Chinese hamster ovary cell chromosome aberration assay and human lymphocyte chromosome aberration assay) and one in vivogenotoxicity test (mouse micronucleus assay).

No evidence of impairment of fertility or effect on mating performance was observed in a fertility and general reproductive performance study conducted in male and female rats at subcutaneous doses up to 50 μg/kg/day (less than the MRHD in adults based on body surface area comparisons).

Store at 20° to 25°C (68° to 77°F)[see USP Controlled Room Temperature].

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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

Advise the patient:

{ "type": "p", "children": [], "text": "Advise the patient:" }

{ "type": "ul", "children": [ "Avoid contact with the eyes.", "Do not bandage the treated skin area, or cover or wrap it to cause occlusion unless directed by the healthcare provider.", "Report any signs of local adverse reaction to their healthcare provider.", "Do not use on the face, underarms, or groin areas unless directed by the healthcare provider." ], "text": "" }

Manufactured by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761 Distributed by: Taro Pharmaceuticals U.S.A., Inc.,Hawthorne, NY 10532 Revised: January 2020

{ "type": "p", "children": [], "text": "Manufactured by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761 \n Distributed by:\n \n Taro Pharmaceuticals U.S.A., Inc.,Hawthorne, NY 10532 \n Revised: January 2020\n\n " }

<div class="scrollingtable"><table width="100%"> <col align="left" valign="top" width="80%"/> <col align="left" valign="top" width="20%"/> <thead> <tr class="First Last"> <th align="center" class="Lrule Rrule" colspan="2">PATIENT INFORMATION <br/> Fluticasone Propionate (floo tik' a sone proe' pee oh nate) Ointment, 0.005% </th> </tr> </thead> <tfoot> <tr class="First Last"> <td align="left">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align="center">Revised: January 2020</td> </tr> </tfoot> <tbody> <tr class="Botrule First"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Important: Fluticasone propionate ointment is for use on skin only (topical).</span>Do not get fluticasone propionate ointment near or in your eyes, mouth, or vagina. <br/> Read this Patient Information before you start using fluticasone propionate ointment 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 your treatment. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What is fluticasone propionate ointment?</span> <br/> Fluticasone propionate ointment is a prescription corticosteroid medicine used on the skin (topical) for the relief of inflammation and itching caused by certain skin conditions in adults. <br/> It is not known if fluticasone propionate ointment is safe and effective in children. Fluticasone propionate ointment is not recommended for use in children. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">Before using fluticasone propionate ointment, tell your healthcare provider about all of your medical conditions, including if you:</span> <ul class="Disc"> <li>have an allergy to any of the ingredients in fluticasone propionate ointment</li> <li>have a skin infection at the site to be treated. You may also need medicine to treat the skin infection.</li> <li>have adrenal gland problems</li> <li>have liver problems</li> <li>have diabetes</li> <li>have thinning skin (atrophy) at the site to be treated</li> <li>are pregnant or plan to become pregnant. It is not known if fluticasone propionate ointment will harm your unborn baby.</li> <li>are breastfeeding or plan to breastfeed. It is not known if fluticasone propionate ointment can pass into your breast milk and harm your baby.</li> </ul> <span class="Bold">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">How should I use fluticasone propionate ointment?</span> <ul class="Disc"> <li>Use fluticasone propionate ointment exactly as your healthcare provider tells you to use it.</li> <li>Apply a thin film of fluticasone propionate ointment to the affected area 2 times each day. Gently rub into your skin.</li> <li>Do not bandage, cover, or wrap the treated area unless your healthcare provider tells you to.</li> <li>Do not use fluticasone propionate ointment on your face, groin, underarms (armpits), unless your healthcare provider tells you to.</li> <li>Wash your hands after applying fluticasone propionate ointment, unless your hands are being treated.</li> <li>Tell your healthcare provider if your symptoms get worse with fluticasone propionate ointment or if your symptoms do not improve after 2 weeks of treatment.</li> </ul> </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What are the possible side effects of fluticasone propionate ointment? <br/> Fluticasone propionate ointment may cause serious side effects, including: </span> <ul class="Disc"> <li> <span class="Bold">Fluticasone propionate ointment can pass through your skin and may</span>cause adrenal gland problems. This is more likely to happen if you use fluticasone propionate ointment for too long, use it over a large treatment area, use it with other topical medicines that contain corticosteroids, cover the treated area, or have liver failure. Your healthcare provider may do blood tests to check your adrenal gland function during and after treatment with fluticasone propionate ointment. </li> <li> <span class="Bold">Skin problems, including skin reactions or thinning of your skin (atrophy), skin infections, and allergic reactions</span>(allergic contact dermatitis) at the treatment site. Tell your healthcare provider if you get any skin reactions such as pain, tenderness, swelling, or healing problems. </li> </ul> <span class="Bold">The most common side effects of fluticasone propionate ointment</span>include itching, burning, excessive hair growth, skin redness, hives, and lightheadedness. <br/> These are not all the possible side effects of fluticasone propionate ointment. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. </td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">How should I store fluticasone propionate ointment?</span> <ul class="Disc"> <li>Store fluticasone propionate ointment between 68°F to 77°F (20°C to 25°C).</li> </ul> <span class="Bold">Keep fluticasone propionate ointment and all medicines out of the reach of children.</span></td> </tr> <tr class="Botrule"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">General information about the safe and effective use of fluticasone propionate ointment</span>. <br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use fluticasone propionate ointment for a condition for which it was not prescribed. Do not give fluticasone propionate ointment 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 information about fluticasone propionate ointment that is written for health professionals. </td> </tr> <tr class="Last"> <td align="left" class="Lrule Rrule" colspan="2"><span class="Bold">What are the ingredients in fluticasone propionate ointment? <br/> Active ingredient: </span>fluticasone propionate <br/> <span class="Bold">Inactive ingredients:</span>microcrystalline wax, mineral oil, propylene glycol and sorbitan sesquioleate <br/> Manufactured by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761 <br/> Distributed by: <span class="Bold">Taro Pharmaceuticals U.S.A., Inc.,</span>Hawthorne, NY 10532 </td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table width=\"100%\">\n<col align=\"left\" valign=\"top\" width=\"80%\"/>\n<col align=\"left\" valign=\"top\" width=\"20%\"/>\n<thead>\n<tr class=\"First Last\">\n<th align=\"center\" class=\"Lrule Rrule\" colspan=\"2\">PATIENT INFORMATION \n <br/> Fluticasone Propionate (floo tik' a sone proe' pee oh nate) Ointment, 0.005%\n </th>\n</tr>\n</thead>\n<tfoot>\n<tr class=\"First Last\">\n<td align=\"left\">This Patient Information has been approved by the U.S. Food and Drug Administration.</td><td align=\"center\">Revised: January 2020</td>\n</tr>\n</tfoot>\n<tbody>\n<tr class=\"Botrule First\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Important: Fluticasone propionate ointment is for use on skin only (topical).</span>Do not get fluticasone propionate ointment near or in your eyes, mouth, or vagina. \n <br/> Read this Patient Information before you start using fluticasone propionate ointment 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 your treatment.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What is fluticasone propionate ointment?</span>\n<br/> Fluticasone propionate ointment is a prescription corticosteroid medicine used on the skin (topical) for the relief of inflammation and itching caused by certain skin conditions in adults. \n <br/> It is not known if fluticasone propionate ointment is safe and effective in children. Fluticasone propionate ointment is not recommended for use in children.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">Before using fluticasone propionate ointment, tell your healthcare provider about all of your medical conditions, including if you:</span>\n<ul class=\"Disc\">\n<li>have an allergy to any of the ingredients in fluticasone propionate ointment</li>\n<li>have a skin infection at the site to be treated. You may also need medicine to treat the skin infection.</li>\n<li>have adrenal gland problems</li>\n<li>have liver problems</li>\n<li>have diabetes</li>\n<li>have thinning skin (atrophy) at the site to be treated</li>\n<li>are pregnant or plan to become pregnant. It is not known if fluticasone propionate ointment will harm your unborn baby.</li>\n<li>are breastfeeding or plan to breastfeed. It is not known if fluticasone propionate ointment can pass into your breast milk and harm your baby.</li>\n</ul>\n<span class=\"Bold\">Tell your healthcare provider about all the medicines you take,</span>including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take other corticosteroid medicines by mouth or use other products on your skin that contain corticosteroids.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">How should I use fluticasone propionate ointment?</span>\n<ul class=\"Disc\">\n<li>Use fluticasone propionate ointment exactly as your healthcare provider tells you to use it.</li>\n<li>Apply a thin film of fluticasone propionate ointment to the affected area 2 times each day. Gently rub into your skin.</li>\n<li>Do not bandage, cover, or wrap the treated area unless your healthcare provider tells you to.</li>\n<li>Do not use fluticasone propionate ointment on your face, groin, underarms (armpits), unless your healthcare provider tells you to.</li>\n<li>Wash your hands after applying fluticasone propionate ointment, unless your hands are being treated.</li>\n<li>Tell your healthcare provider if your symptoms get worse with fluticasone propionate ointment or if your symptoms do not improve after 2 weeks of treatment.</li>\n</ul>\n</td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What are the possible side effects of fluticasone propionate ointment? \n <br/> Fluticasone propionate ointment may cause serious side effects, including:\n </span>\n<ul class=\"Disc\">\n<li>\n<span class=\"Bold\">Fluticasone propionate ointment can pass through your skin and may</span>cause adrenal gland problems. This is more likely to happen if you use fluticasone propionate ointment for too long, use it over a large treatment area, use it with other topical medicines that contain corticosteroids, cover the treated area, or have liver failure. Your healthcare provider may do blood tests to check your adrenal gland function during and after treatment with fluticasone propionate ointment.\n \n </li>\n<li>\n<span class=\"Bold\">Skin problems, including skin reactions or thinning of your skin (atrophy), skin infections, and allergic reactions</span>(allergic contact dermatitis) at the treatment site. Tell your healthcare provider if you get any skin reactions such as pain, tenderness, swelling, or healing problems.\n \n </li>\n</ul>\n<span class=\"Bold\">The most common side effects of fluticasone propionate ointment</span>include itching, burning, excessive hair growth, skin redness, hives, and lightheadedness. \n <br/> These are not all the possible side effects of fluticasone propionate ointment. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.\n \n </td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">How should I store fluticasone propionate ointment?</span>\n<ul class=\"Disc\">\n<li>Store fluticasone propionate ointment between 68°F to 77°F (20°C to 25°C).</li>\n</ul>\n<span class=\"Bold\">Keep fluticasone propionate ointment and all medicines out of the reach of children.</span></td>\n</tr>\n<tr class=\"Botrule\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">General information about the safe and effective use of fluticasone propionate ointment</span>. \n <br/> Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use fluticasone propionate ointment for a condition for which it was not prescribed. Do not give fluticasone propionate ointment 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 information about fluticasone propionate ointment that is written for health professionals.\n \n </td>\n</tr>\n<tr class=\"Last\">\n<td align=\"left\" class=\"Lrule Rrule\" colspan=\"2\"><span class=\"Bold\">What are the ingredients in fluticasone propionate ointment? \n <br/> Active ingredient:\n </span>fluticasone propionate \n <br/>\n<span class=\"Bold\">Inactive ingredients:</span>microcrystalline wax, mineral oil, propylene glycol and sorbitan sesquioleate \n <br/> Manufactured by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 2624761 \n <br/> Distributed by:\n \n <span class=\"Bold\">Taro Pharmaceuticals U.S.A., Inc.,</span>Hawthorne, NY 10532\n \n </td>\n</tr>\n</tbody>\n</table></div>" }

NDC 51672-4095-3

{ "type": "p", "children": [], "text": "\nNDC 51672-4095-3\n" }

60 g

{ "type": "p", "children": [], "text": "\n60 g\n" }

Fluticasone Propionate Ointment USP, 0.005%

{ "type": "p", "children": [], "text": "\nFluticasone Propionate \n Ointment USP, 0.005%\n \n" }

FOR DERMATOLOGIC USE ONLY. NOT FOR OPHTHALMIC USE.

{ "type": "p", "children": [], "text": "FOR DERMATOLOGIC USE ONLY. \n NOT FOR OPHTHALMIC USE.\n " }

Rx only

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

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

{ "type": "p", "children": [], "text": "\nKeep this and all medications out of the reach of children.\n" }

TARO

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