FDA

Fluticasone Propionate

Approved 22 Feb 2006NasalSpray, metered

The FDA lists this product in 24 strengths and forms.

Indications

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. Fluticasone propionate nasal spray is a corticosteroid indicated for the management of the nasal symptoms of perennial nonallergic rhinitis in adult and pediatric patients aged 4 years and older. ( 1 )

Contraindications

Fluticasone propionate nasal spray is contraindicated in patients with hypersensitivity to any of its ingredients [see Warnings and Precautions (5.3) , Description (11)] . Hypersensitivity to any ingredient. ( 4 )

Warnings and precautions

Epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, and impaired wound healing. Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma. ( 5.1 )
Glaucoma and cataracts: Consider referral to an ophthalmologist in patients who develop ocular symptoms or use fluticasone propionate nasal spray long-term. ( 5.2 )
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. ( 5.3 )
Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.4 )
Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue fluticasone propionate nasal spray slowly. ( 5.5 )
Monitor growth of pediatric patients. ( 5.7 )

5.1Local Nasal Effects

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)] . Candida Infection : In clinical trials with fluticasone propionate administered intranasally, the development of localized infections of the nose and pharynx with Candida albicans has occurred.

At a glance

Brand name: Fluticasone Propionate
Route: Nasal
Dosage form: Spray, metered
Applicant: Hikma
Status: Prescription
FDA approval: 22 Feb 2006
Application: ANDA076504-001

Indications

Warnings and precautions

Epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, and impaired wound healing. Monitor patients periodically for signs of adverse effects on the nasal mucosa. Avoid use in patients with recent nasal ulcers, nasal surgery, or nasal trauma. ( 5.1 )
Glaucoma and cataracts: Consider referral to an ophthalmologist in patients who develop ocular symptoms or use fluticasone propionate nasal spray long-term. ( 5.2 )
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. ( 5.3 )
Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.4 )
Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue fluticasone propionate nasal spray slowly. ( 5.5 )
Monitor growth of pediatric patients. ( 5.7 )

5.1Local Nasal Effects

Pregnancy and breastfeeding

8.1Pregnancy 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).

Adverse reactions

Systemic and local corticosteroid use may result in the following:

Epistaxis, nasal ulceration, Candida albicans infection, nasal septal perforation, and impaired wound healing [see Warnings and Precautions (5.1)]
Glaucoma and cataracts [see Warnings and Precautions (5.2)]
Immunosuppression [see Warnings and Precautions (5.4)]
Hypercorticism and adrenal suppression [see Warnings and Precautions (5.5)]
Effect on growth [see Warnings and Precautions (5.7)] The most common adverse reactions (>3%) are headache, pharyngitis, epistaxis, nasal burning/nasal irritation, nausea/vomiting, asthma symptoms, and cough. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

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 Adverse Reaction Fluticasone Propionate 100 mcg Once Daily (N = 167) % Fluticasone Propionate 200 mcg Once Daily (N = 782) % Placebo (N = 758) % Headache 6.6 16.1

14.6 Pharyngitis 6 7.8

7.2 Epistaxis 6 6.9

5.4 Nasal Burning/Nasal Irritation 2.4 3.2

2.6 Nausea/Vomiting 4.8 2.6 2 Asthma Symptoms 7.2 3.3

2.9 Cough 3.6 3.8

2.8 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.

6.2Postmarketing Experience

In addition to adverse events reported from clinical trials, the following adverse events have been identified during postapproval 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

Indications

Contraindications

Warnings and precautions

5.1Local Nasal Effects

At a glance

Two medicines in one question?

Fluticasone Propionate

Indications

Contraindications

Warnings and precautions

5.1Local Nasal Effects

At a glance

Two medicines in one question?

5.2Glaucoma and Cataracts Use

5.3Hypersensitivity

5.4Immunosuppression

5.5Hypercorticism and Adrenal Suppression

5.6Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors

5.7Effect on Growth

Interactions

7.1Inhibitors of Cytochrome P450 3A4

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information