Fluticasone

ADVERSE REACTIONS Clinical Trial Experience – In controlled clinical trials of twice-daily administration, the total incidence of adverse reactions associated with the use of fluticasone propionate cream, 0.05% was approximately 4%. These adverse reactions were usually mild; self-limiting; and consisted primarily of pruritus, dryness, numbness of fingers, and burning. These events occurred in 2.9%, 1.2%, 1.0%, and 0.6% of patients, respectively. Two clinical studies compared once- to twice-daily administration of fluticasone propionate cream, 0.05% for the treatment of moderate to severe eczema. The local drug-related adverse events for the 491 patients enrolled in both studies are shown in Table 1. In the study enrolling both adult and pediatric patients, the incidence of local adverse events in the 119 pediatric patients ages 1 to 12 years was comparable to the 140 patients ages 13 to 62 years. Fifty-one pediatric patients ages 3 months to 5 years, with moderate to severe eczema, were enrolled in an open-label HPA axis safety study. Fluticasone propionate cream, 0.05% was applied twice daily for 3 to 4 weeks over an arithmetic mean body surface area of 64% (range, 35% to 95%). The mean morning cortisol levels with standard deviations before treatment (prestimulation mean value = 13.76 ± 6.94 mcg/dL, poststimulation mean value = 30.53 ± 7.23 mcg/dL) and at end treatment (prestimulation mean value = 12.32 ± 6.92 mcg/dL, poststimulation mean value = 28.84 ± 7.16 mcg/dL) showed little change. In 2 of 43 (4.7%) patients with end-treatment results, peak cortisol levels following cosyntropin stimulation testing were ≤18 μg/dL, indicating adrenal suppression. Follow-up testing after treatment discontinuation, available for 1 of the 2 subjects, demonstrated a normally responsive HPA axis. Local drug-related adverse events were transient burning, resolving the same day it was reported; transient urticaria, resolving the same day it was reported; erythematous rash; dusky erythema, resolving within 1 month after cessation of fluticasone propionate cream, 0.05%; and telangiectasia, resolving within 3 months after stopping fluticasone propionate cream, 0.05%. Table 1: Drug-Related Adverse Events-Skin Adverse Events Fluticasone Once Daily (n = 210) Fluticasone Twice Daily (n = 203) Vehicle Twice Daily (n = 78) Skin infection Infected eczema Viral warts Herpes simplex Impetigo Atopic dermatitis Eczema Exacerbation of eczema Erythema Burning Stinging Skin irritation Pruritus Exacerbation of pruritus Folliculitis Blisters Dryness of skin 1 (0.5%) 1 (0.5%) 0 0 1 (0.5%) 1 (0.5%) 1 (0.5%) 4 (1.9%) 0 2 (1.0%) 0 6 (2.9%) 2 (1.0%) 4 (1.9%) 1 (0.5%) 0 3 (1.4%) 0 2 (1.0%) 1 (0.5%) 1 (0.5%) 0 0 0 1 (0.5%) 2 (1.0%) 2 (1.0%) 2 (1.0%) 2 (1.0%) 4. (1.9%) 1 (0.5%) 1 (0.5%) 1 (0.5%) 1 (0.5%) 0 0 0 0 0 0 0 1 (1.3%) 0 2 (2.6%) 1 (1.3%) 0 4 (5.1%) 1 (1.3%) 0 0 0 Table 2: Adverse Events* From Pediatric Open-Label Trial (n=51) Adverse Events Fluticasone Twice Daily Burning Dusky erythema Erythematous rash Facial telangiectasia† Non-facial telangiectasia Urticaria 1 (2.0%) 1 (2.0%) 1 (2.0%) 2 (4.9%) 1 (2.0%) 1 (2.0%) * See text for additional detail. † n=41. Post Marketing Experience – Systemic adverse events with fluticasone propionate cream, 0.05% and fluticasone propionate ointment have included: immunosuppression/Pneumocystis carinii pneumonia/leukopenia/thrombocytopenia; hyperglycemia/glycosuria; Cushing’s syndrome; generalized body edema/blurred vision; and acute urticarial reaction (edema, urticaria, pruritus, and throat swelling). The following localized adverse reactions have been reported during post approval use of fluticasone propionate cream, 0.05%: skin discoloration, erythema, irritation, edema/swelling, atrophy, contusion, dermatitis, pain, sepsis, hemorrhage, acneiform eruptions. 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.

Pediatric Use – Fluticasone Propionate Cream, 0.05% contains the excipient imidurea which releases formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitization or irritation upon contact with the skin. Fluticasone Propionate Cream, 0.05% should not be used in individuals with hypersensitivity to formaldehyde as it may prevent healing or worsen dermatitis. Fluticasone Propionate Cream, 0.05% should be discontinued if control is achieved before 4 weeks. If no improvement is seen within 2 weeks, contact a physician. The safety and efficacy of drug use for longer than 4 weeks in this population have not been established. The safety and efficacy of Fluticasone Propionate Cream, 0.05% in pediatric patients below 3 months of age have not been established. Parents of pediatric patients should be advised not to use this medication in the treatment of diaper dermatitis unless directed by the physician. Fluticasone Propionate Cream, 0.05% should not be applied in the diaper areas as diapers or plastic pants may constitute occlusive dressing. Fluticasone propionate cream, 0.05% caused HPA axis suppression in 2 of 43 pediatric patients, ages 2 and 5 years old, who were treated for 4 weeks covering at least 35% of the body surface area. Follow-up testing 12 days after treatment discontinuation, available for 1 of the 2 subjects, demonstrated a normally responsive HPA axis (see ADVERSE REACTIONS ). Adverse effects including striae have been reported with use of topical corticosteroids in pediatric patients. HPA axis suppression, Cushing’s syndrome, linear growth retardation, delayed weight gain, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include low plasma cortisol levels to an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.