FLUTICASONE PROPIONATE

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

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 year of age and older. ( 1 )

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. )

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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 fluticasone propionate lotion had marked elevations of the hepatic enzymes AST and ALT. [see Use in Specific Populations ( 8.4 )] In another open label HPA axis suppression trial in which fluticasone propionate lotion was also applied twice daily (rather than the indicated dosing regimen of once daily), 56 pediatric subjects (ages ≥3 months to 12 months), were enrolled [see Use in Specific Populations ( 8.4 )] . The adverse reactions included 2 cases of Herpes simplex at the application site (3.6%) and 3 cases of bacterial skin infections (5.4%). 6.3Postmarketing Experience The following local adverse reactions have been identified during post-approval use of fluticasone propionate lotion: erythema, edema/swelling, and bleeding. The following systemic adverse reactions have been identified during post-approval use of fluticasone propionate cream and 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, and they may occur more frequently with the use of occlusive dressings or higher potency corticosteroids. These reactions include: acneiform eruptions, hypopigmentation, perioral dermatitis, skin atrophy, striae, hypertrichosis 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.