Fluticasone Propionate

Warnings and Precautions, Ophthalmic Adverse Reaction ( 5.5 ) 03/2021

1 INDICATIONS AND USAGE Fluticasone propionate ointment, USP 0.005% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adult patients. Fluticasone propionate ointment, USP 0.005% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in adult patients. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a thin film of fluticasone propionate ointment to the affected skin areas twice daily. Rub in gently. Avoid use with occlusive dressing. Fluticasone propionate ointment is for topical use only; it is not for ophthalmic, oral, or intravaginal use. Apply a thin film to affected skin areas twice daily. ( 2 ) Not for ophthalmic, oral or intravaginal use. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Ointment, 0.005%. Each gram of fluticasone propionate ointment, 0.005% contains 0.05 mg fluticasone propionate in a white to off-white translucent ointment base. Fluticasone propionate ointment, 0.005% is supplied in 15 g, 30 g, and 60 g tubes. Ointment, 0.005%, supplied in 15 g, 30 g, and 60 g tubes. ( 3 )

4 CONTRAINDICATIONS Fluticasone propionate ointment, 0.005% is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation. Fluticasone propionate ointment, 0.005% is contraindicated in those patients with a history of serious hypersensitivity to any of the components in the preparation. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • HPA Axis Suppression and Other Adverse Endocrine Effects [see Warnings and Precautions ( 5.1 ) ] • Local Adverse Reactions [see Warnings and Precautions ( 5.2 ) ] • Concomitant Skin Infections [see Warnings and Precautions ( 5.4 ) ] The most common adverse reactions (<1%) were pruritus, burning, hypertrichosis, increased erythema, urticaria, irritation, and lightheadedness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 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 subjects. 6.2 Postmarketing Experience 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. 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 ointment: immunosuppression/ Pneumocystis jirovecii /pneumonia/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. Ophthalmic adverse reactions including cataracts, glaucoma and increased intraocular pressure have been reported with the use of topical corticosteroids.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available data on fluticasone propionate ointment use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Observational studies suggest an increased risk of low birthweight infants with the use of greater than 300 grams of potent or very potent topical corticosteroids during pregnancy (see Data) . Advise pregnant women that fluticasone propionate ointment may increase the risk of having a low birthweight infant and to use fluticasone propionate ointment on the smallest area of skin and for the shortest duration possible. In animal reproduction studies, subcutaneous administration of fluticasone propionate to pregnant mice, rats, and rabbits during organogenesis caused malformations characteristic of corticosteroids in each species (see Data) . The available data do not allow the calculation of relevant comparisons between the systemic exposure of fluticasone propionate observed in animal studies to the systemic exposure that would be expected in humans after topical use of fluticasone propionate ointment. The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data Available observational studies in pregnant women did not identify a drug-associated risk of major birth defects, preterm delivery, or fetal mortality with the use of topical corticosteroids of any potency. However, when the dispensed amount of potent or very potent topical corticosteroids exceeded 300 grams during the entire pregnancy, maternal use was associated with an increased risk of low birth weight infants. Animal Data In embryo-fetal development studies, pregnant rabbits, rats, and mice received subcutaneous doses of fluticasone propionate during organogenesis at doses up to 4, 100, and 150 μg/kg/day, respectively. A malformation characteristic of corticosteroids (cleft palate) was noted at the high dose in each species. Additional adverse effects were noted in rats and rabbits. Decreased fetal weights and retarded skeletal ossification were noted in rabbits at 4 μg/kg/day and rats at 100 μg/kg/day. Maternal toxicity and omphalocele were also noted in rats at 100 μg/kg/day. No malformations or developmental toxicity was noted in rabbits at 0.57 μg/kg/day, in rats at 10 μg/kg/day, or in mice at 15 μg/kg/day. Fluticasone propionate crossed the placenta following administration of a subcutaneous or an oral dose of 100 μg/kg tritiated fluticasone propionate to pregnant rats. 8.2 Lactation Risk Summary There are no data on the presence of fluticasone propionate in human milk, its effects on the breastfed infant, or its effects on milk production. It is not known whether topical administration of fluticasone propionate ointment could result in sufficient systemic absorption to produce detectable quantities in human milk (see Clinical Considerations ). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for fluticasone propionate ointment and any potential adverse effects on the breastfed child from fluticasone propionate ointment or from the underlying maternal condition. Clinical Considerations To minimize potential exposure to the breastfed infant via breast milk, use fluticasone propionate ointment on the smallest area of skin and for the shortest duration possible while breastfeeding. Advise breastfeeding women not to apply fluticasone propionate ointment directly to the nipple and areola prior to breastfeeding to avoid direct infant exposure [see Use in Specific Populations ( 8.4 ) ]. 8.4 Pediatric Use The safety and effectiveness …

12.1 Mechanism of Action Corticosteroids play a role in cellular signaling, immune function, inflammation, and protein regulation; however, the precise mechanism of action of fluticasone propionate ointment, 0.005% in corticosteroid-responsive dermatoses is unknown.

11 DESCRIPTION Fluticasone Propionate Ointment, 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. Chemically, fluticasone propionate is C 25 H 31 F 3 O 5 S. It has the following structural formula: 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 contains fluticasone propionate 0.05 mg in a white to off-white translucent ointment base of liquid paraffin, microcrystalline wax, propylene glycol, and sorbitan sesquioleate. Structural Formula Image

16 HOW SUPPLIED/STORAGE AND HANDLING Fluticasone Propionate Ointment, 0.005% is a white to off-white translucent ointment supplied as follows: NDC: 72162-1401-2: 15 g in a TUBE NDC: 72162-1401-3: 30 g in a TUBE NDC: 72162-1401-6: 60g in a TUBE Store at 20-25°C (68-77°F) Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504