Fluticasone Propionate Nasal Spray, USP, 50 MCG

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Fluticasone propionate, the active component of Fluticasone Propionate Nasal Spray, USP, is a synthetic corticosteroid having the chemical name -(fluoromethyl) 6α,9-difluoro-11β-17-dihydroxy- 16α-methyl-3-oxoandrosta-1,4- diene-17β-carbothioate, 17-propionate and the following chemical structure:
S Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empirical formula is C H F O S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol.
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5 Fluticasone Propionate Nasal Spray, USP, 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, USP, also contains benzalkonium chloride (0.02% w/w), carboxymethylcellulose sodium,dextrose, microcrystalline cellulose, phenylethyl alchol (0.25% w/w), polysorbate 80, and purified water and has a pH between 5.8 and 6.8. It is necessary to prime the pump before first use or after a period of non-use (1 week or more). After initial priming (6 actuations), each actuation delivers 50 mcg of fluticasone propionate in 100 mg of formulation through the nasal adapter. Each 16-g bottle of Fluticasone Propionate Nasal Spray, USP, provides 120 metered sprays. After 120 metered sprays, the amount of fluticasone propionate delivered per actuation may not be consistent and the unit should be discarded.

CLINICAL TRIALS

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displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

A total of 13 randomized, double-blind, parallel-group, multicenter, vehicle placebo-controlled clinical trials were conducted in the United States in adults and pediatric patients (4 years of age and older) to investigate regular use of Fluticasone Propionate Nasal Spray, USP, in patients with seasonal or perennial allergic rhinitis. The trials included 2,633 adults (1,439 men and 1,194 women) with a mean age of 37 (range, 18 to 79 years). A total of 440 adolescents (405 boys and 35 girls), mean age of 14 (range, 12 to 17 years), and 500 children (325 boys and 175 girls), mean age of 9 (range, 4 to 11 years) were also studied. The overall racial distribution was 89% white, 4% black, and 7% other. These trials evaluated the total nasal symptom scores (TNSS) that included rhinorrhea, nasal obstruction, sneezing, and nasal itching in known allergic patients who were treated for 2 to 24 weeks. Subjects treated with Fluticasone Propionate Nasal Spray, USP exhibited significantly greater decreases in TNSS than vehicle placebo-treated patients. Nasal mucosal basophils and eosinophils were also reduced at the end of treatment in adult studies; however, the clinical significance of this decrease is not known. There were no significant differences between fluticasone propionate regimens whether administered as a single daily dose of 200 mcg (two 50-mcg sprays in each nostril) or as 100 mcg (one 50-mcg spray in each nostril) twice daily in 6 clinical trials. A clear dose response could not be identified in clinical trials. In 1 trial, 200 mcg/day was slightly more effective than 50 mcg/day during the first few days of treatment; thereafter, no difference was seen. Two randomized, double-blind, parallelgroup, multicenter, vehicle placebo-controlled 28-day trials were conducted in the United States in 732 patients (243 given Fluticasone Propionate Nasal Spray, USP) 12 years of age and older to investigate “as-needed” use of Fluticasone Propionate Nasal Spray, USP (200 mcg) in patients with seasonal allergic rhinitis. Patients were instructed to take the study medication only on days when they thought they needed the medication for symptom control, not to exceed 2 sprays per nostril on any day, and not more than once daily. “Asneeded” use was prospectively defined as average use of study medication no more than 75% of study days. Average use of study medications was 57% to 70% of days for all treatment arms. The studies demonstrated significantly greater reduction in TNSS (sum of nasal congestion, rhinorrhea, sneezing, and nasal itching) with Fluticasone Propionate Nasal Spray, USP, 200 mcg compared to placebo. The relative difference in efficacy with as-needed use as compared to regularly administered doses was not studied. Three randomized, double-blind, parallel- group, vehicle placebo-controlled trials were conducted in 1,191 patients to investigate regular use of Fluticasone Propionate Nasal Spray, USP, in patients with perennial nonallergic rhinitis. These trials evaluated the patient-rated TNSS (nasal obstruction, postnasal drip, rhinorrhea) in patients treated for 28 days of doubleblind therapy and in 1 of the 3 trials for 6 months of open-label treatment. Two of these trials demonstrated that patients treated with Fluticasone Propionate Nasal Spray, USP, at a dosage of 100 mcg twice daily exhibited statistically significant decreases in TNSS compared with patients treated with vehicle.

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Fluticasone Propionate Nasal Spray, USP, is indicated for the management of the nasal symptoms of seasonal and perennial allergic and nonallergic rhinitis in adults and pediatric patients 4 years of age and older. Safety and effectiveness of Fluticasone Propionate Nasal Spray, USP, in children below 4 years of age have not been adequately established.

CONTRAINDICATIONS

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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Fluticasone Propionate Nasal Spray, USP, is contraindicated in patients with a hypersensitivity to any of its ingredients.

WARNINGS

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displayName: WARNINGS SECTION
FDA Article Code: 34071-1

The replacement of a systemic corticosteroid with a topical corticosteroid can be accompanied by signs of adrenal insufficiency, and in addition some patients may experience symptoms of withdrawal, e.g., joint and/or muscular pain, lassitude, and 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 those patients who have asthma or other clinical conditions requiring long-term systemic corticosteroid treatment, too rapid a decrease in systemic corticosteroids may cause a severe exacerbation of their symptoms. The concomitant use of intranasal corticosteroids with other inhaled corticosteroids could increase the risk of signs or symptoms of hypercorticism and/or suppression of the HPA axis. A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations (see and ). 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 syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
CLINICAL PHARMACOLOGY: Drug Interactions
PRECAUTIONS: Drug Interactions 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 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 exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If 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. Avoid spraying in eyes.

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. In controlled US studies, more than 3,300 patients with seasonal allergic, perennial allergic, or perennial nonallergic rhinitis received treatment with intranasal fluticasone propionate. In general, adverse reactions in clinical studies have been primarily associated with irritation of the nasal mucous membranes, and the adverse reactions were reported with approximately the same frequency by patients treated with the vehicle itself. The complaints did not usually interfere with treatment. Less than 2% of patients in clinical trials discontinued because of adverse events; this rate was similar for vehicle placebo and active comparators. Systemic corticosteroid side effects were not reported during controlled clinical studies up to 6 months’ duration with Fluticasone Propionate Nasal Spray, USP. If recommended doses are exceeded, however, or if individuals are particularly sensitive or taking Fluticasone Propionate Nasal Spray, USP, in conjunction with administration of other corticosteroids, symptoms of hypercorticism, e.g., Cushing syndrome, could occur. The following incidence of common adverse reactions (>3%, where incidence in fluticasone propionate-treated subjects exceeded placebo) is based upon 7 controlled clinical trials in which 536 patients (57 girls and 108 boys aged 4 to 11 years, 137 female and 234 male adolescents and adults) were treated with Fluticasone Propionate Nasal Spray, USP, 200 mcg once daily over 2 to 4 weeks and 2 controlled clinical trials in which 246 patients (119 female and 127 male adolescents and adults) were treated with Fluticasone Propionate Nasal Spray, USP, 200 mcg once daily over 6 months. Also included in the table are adverse events from 2 studies in which 167 children (45 girls and 122 boys aged 4 to 11 years) were treated with Fluticasone Propionate Nasal Spray, USP, 100 mcg once daily for 2 to 4 weeks.

OVERDOSAGE

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displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

Chronic overdosage may result in signs/symptoms of hypercorticism (see ). Intranasal administration of 2 mg (10 times the recommended dose) of fluticasone propionate twice daily for 7 days to healthy human volunteers was well tolerated. 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 1 bottle of Fluticasone Propionate Nasal Spray, USP, contains approximately 8 mg of fluticasone propionate.
PRECAUTIONS The oral and subcutaneous median lethal doses in mice and rats were >1,000 mg/kg (>20,000 and >41,000 times, respectively, the maximum recommended daily intranasal dose in adults and >10,000 and >20,000 times, respectively, the maximum recommended daily intranasal dose in children on a mg/m basis).
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DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Patients should use Fluticasone Propionate Nasal Spray, USP, at regular intervals for optimal effect.

PATIENT INSTRUCTIONS FOR USE

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displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5

Please read this leaflet carefully before you start to take your medicine. It provides a summary of information on your medicine.

For further information ask your doctor or pharmacist.

FLUTICASONE PROPIONATE SPRAY, METERED

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4