Fluticasone Propionate

1 INDICATIONS AND USAGE Fluticasone propionate lotion is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of atopic dermatitis in patients 3 months of age or older. Fluticasone propionate lotion is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of atopic dermatitis in patients 3 months of age and older. ( 1 )

2 DOSAGE AND ADMINISTRATION Apply a thin film of fluticasone propionate lotion to the affected skin areas once daily. Rub in gently. Discontinue use when control is achieved. If no improvement is seen within 2 weeks, reassessment of the diagnosis may be necessary. The safety and efficacy of fluticasone propionate lotion have not been established beyond 4 weeks of use. Avoid use with occlusive dressings or application to the diaper area [ see Warnings and Precautions ( Error! Hyperlink reference not valid. ) and ( Error! Hyperlink reference not valid. ) ]. Fluticasone propionate lotion is for topical use only, and not for ophthalmic, oral, or intravaginal use. • Apply a thin film to the affected skin areas once daily. Rub in gently. ( Error! Hyperlink reference not valid. ) • Discontinue use when control is achieved. ( Error! Hyperlink reference not valid. ) • Reassess diagnosis if no improvement in 2 weeks. ( Error! Hyperlink reference not valid. ) • The safety and efficacy of fluticasone propionate lotion have not been established beyond four weeks of use. ( Error! Hyperlink reference not valid. ) • Avoid use under occlusion or application to diaper area. ( Error! Hyperlink reference not valid. ) • Not for ophthalmic, oral, or intravaginal use. ( Error! Hyperlink reference not valid. )

3 DOSAGE FORMS AND STRENGTHS Lotion, 0.05%. Each gram of fluticasone propionate lotion USP contains 0.5 mg fluticasone propionate USP in a white translucent smooth homogeneous lotion. Fluticasone propionate lotion USP is supplied in 60 mL bottles. • Lotion, 0.05%, supplied in 60 mL bottles. ( Error! Hyperlink reference not valid. )

4 CONTRAINDICATIONS None. • None ( Error! Hyperlink reference not valid. )

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 ( Error! Hyperlink reference not valid. )]. • Local Adverse Reactions [see Warnings and Precautions ( Error! Hyperlink reference not valid. )]. • Concomitant Skin Infections [see Warnings and Precautions ( Error! Hyperlink reference not valid. )]. The most common adverse reactions (2%) were burning/stinging at the application site. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Glenmark Pharmaceuticals Inc., USA at 1 (888) 721-7115 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience: Controlled Clinical Trials 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 2 multicenter vehicle-controlled clinical trials of once-daily application of fluticasone propionate lotion by 196 adult and 242 pediatric patients, the total incidence of adverse reactions considered drug related by investigators was approximately 4%. These were local cutaneous reactions, usually mild and self-limiting, and consisted primarily of burning/stinging (2%). All other drug-related events occurred with an incidence of less than 1%, and included were contact dermatitis, exacerbation of atopic dermatitis, folliculitis of legs, pruritus, pustules on arm, rash, and skin infection. See Table 1. The incidence of adverse reactions between the 242 pediatric subjects (age 3 months to < 17 years) and 196 adult subjects (17 years or older) was similar (4% and 5%, respectively). Table 1: Adverse Reactions from Controlled Clinical Trials (n=438) ADVERSE REACTIONS Fluticasone Propionate Lotion VEHICLE n=221 n=217 Burning/Stinging skin 4 (2%) 3 (1%) Contact Dermatitis 0 1 (<1%) Exacerbation of Atopic dermatitis 0 1 (<1%) Folliculitis of legs 2 (<1%) 0 Irritant Contact Dermatitis 0 1 (<1%) Pruritus 1 (<1%) 1 (<1%) Pustules on Arms 1 (<1%) 0 Rash 1 (<1%) 2 (<1%) Skin Infection 0 3 (1%) During the clinical trials, eczema herpeticum occurred in a 33-year old male patient treated with fluticasone propionate lotion. Table 2 summarizes all adverse events by body system that occurred in at least 1% of patients in either the drug or vehicle group in the phase 3 controlled clinical trials. Table 2: Adverse Events Occurring in ≥ 1% of Patients from Either Arm from Controlled Clinical Trials (n=438) Body System Fluticasone propionate lotion Vehicle Lotion N = 221 N = 217 Any Adverse Event 77 (35%) 82 (38%) Skin Burning and Stinging 4 (2%) 3 (1%) Pruritus 3 (1%) 5 (2%) Rash 2 (<1%) 3 (1%) Skin Infection 0 3 (1%) Ear, Nose, Throat Common Cold 9 (4%) 5 (2%) Ear Infection 3 (1%) 3 (1%) Nasal Sinus Infection 2 (<1%) 4 (2%) Rhinitis 1 (<1%) 3 (1%) Upper Respiratory Tract Infection 6 (3%) 7 (3%) Gastrointestinal Normal Tooth Eruption 2 (< 1%) 3 (1%) Diarrhea 3 (1%) 0 Vomiting 3 (1%) 2 (<1%) Lower Respiratory Cough 7 (3%) 6 (3%) Influenza 5 (2%) 0 Wheeze 0 3 (1%) Neurology Headache 4 (2%) 5 (2%) Non-Site Specific Fever 8 (4%) 8 (4%) Seasonal Allergy 2 (<1%) 3 (1%) 6.2 Clinical Trials Experience: Pediatric Open Label Trials In an open label HPA axis suppression trial of 44 pediatric subjects (ages ≥3 months to ≤6 years) fluticasone propionate lotion was applied twice daily (rather than the indicated dosing regimen of once daily) to at least 35% of body surface area for 3 or 4 weeks. Subjects whose lesions cleared after 2 or 3 weeks of treatment continued to apply fluticasone propionate lotion for an additional week. The overall incidence of adverse reactions was 14%. These were local, cutaneous reactions and included dry skin (7%), stinging at application site (5%), and excoriation (2%). Additionally, a 4-month-old patient treated with flutica …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Therefore, fluticasone propionate lotion 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, 45 and 150 mcg/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 and 150 mcg/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 mcg/kg/day (less than the MRHD in adults based on body surface area comparisons). Subcutaneous doses of 10, 30 and 100 mcg/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 mcg/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 mcg/kg/day (less than the MRHD in adults based on body surface area comparisons). Subcutaneous doses of 0.08, 0.57 and 4 mcg/kg/day of fluticasone propionate were administered to pregnant female rabbits from gestation days 6 to 18. Fetal effects noted at 4 mcg/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 mcg/kg/day (less than the MRHD in adults based on body surface area comparisons). Oral doses of 3, 30 and 300 mcg/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 mcg/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. 8.3 Nursing Mothers 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 lotion is administered to a nursing woman. 8.4 Pediatric Use Fluticasone propionate lotion may be used in pediatric patients as young as 3 months of age. The safety and effectiveness of fluticasone propionate lotion in pediatric patients below 3 months of age have not been established. 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 an HPA axis suppression trial, none of the 40 evaluable pediatric subjects, 4 months old to < 6 years old, with moderate to severe atopic dermatitis covering ≥ 35% Body Surface Area (BSA) who we …

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 lotion in atopic dermatitis is unknown.

11 DESCRIPTION Fluticasone propionate lotion USP, 0.05% contains fluticasone propionate USP 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. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents. Chemically, fluticasone propionate USP is C 25 H 31 F 3 O 5 S. It has the following structural formula: Fluticasone propionate USP is a white or almost white powder with a molecular weight of 500.6 g/mol. It is freely soluble in dimethylformamide; slightly soluble in alcohol; sparingly soluble in acetone and in dichloromethane; insoluble in water. Each gram of fluticasone propionate lotion USP contains 0.5 mg fluticasone propionate USP in a base of cetostearyl alcohol, polyoxyl 20 cetostearyl ether, citric acid anhydrous, dimethicone 360, isopropyl myristate, light mineral oil, propylene glycol, sodium citrate anhydrous, sorbitan monostearate, and purified water, with imidurea, methylparaben, and propylparaben as preservatives. chemical-structure

16 HOW SUPPLIED/STORAGE AND HANDLING Fluticasone propionate lotion USP, 0.05% is a white translucent smooth homogeneous lotion supplied in HDPE and PP bottles as follows: 60 mL bottles: (NDC 68462-427-02) Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Do not refrigerate. Keep container tightly sealed.