FLUTICASONE PROPIONATE CREAM, 0.05%

Rx only

FOR DERMATOLOGIC USE ONLY
NOT FOR OPHTHALMIC USE

Fluticasone Propionate Cream, 0.05% contains fluticasone propionate [(6α,11β,16α,17α)-6,9-difluoro-11-hydroxy-16-methyl-3-oxo-17-(1-oxopropoxy)androsta-1,4-diene-17-carbothioic acid S-fluoromethyl ester], a synthetic fluorinated corticosteroid, for topical dermatologic use. The topical corticosteroids constitute a class of primarily synthetic steroids used as anti-inflammatory and antipruritic agents.

Chemically, fluticasone propionate is C₂₅H₃₁F₃O₅S. 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 Cream, 0.05% contains fluticasone propionate 0.5 mg in a base of propylene glycol, mineral oil, cetostearyl alcohol, Ceteth-20, isopropyl myristate, dibasic sodium phosphate, citric acid, purified water and imidurea as preservative.

Like other topical corticosteroids, fluticasone propionate has anti-inflammatory, antipruritic and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A₂ inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A₂.

Fluticasone propionate is lipophilic and has a strong affinity for the glucocorticoid receptor. It has weak affinity for the progesterone receptor, and virtually no affinity for the mineralocorticoid, estrogen, or androgen receptors. The therapeutic potency of glucocorticoids is related to the half-life of the glucocorticoid-receptor complex. The half-life of the fluticasone propionate-glucocorticoid receptor complex is approximately 10 hours.

Studies performed with Fluticasone Propionate Cream, 0.05% indicate that it is in the medium range of potency as compared with other topical corticosteroids.

Fluticasone Propionate Cream, 0.05% is a medium potency corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Fluticasone Propionate Cream, 0.05% may be used with caution in pediatric patients 3 months of age or older. The safety and efficiency 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.

Fluticasone Propionate Cream, 0.05% is contraindicated in those patients with a history of hypersensitivity to any of the components in the preparation.

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 and arithmetic mean body surface area of 64% (range 35-95%).

The mean morning cortisol levels with standard deviations before treatment (pre-stimulation mean value = 13.76 ^± 6.94 mcg/dL, post-stimulation mean value = 30.53 ^± 7.23 mcg/dL) and at end treatment (pre-stimulation 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 ug/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 one month after cessation of Fluticasone Propionate Cream, 0.05%; and telangiectasia resolving within 3 months after stopping Fluticasone Propionate Cream, 0.05%.

The following local adverse reactions have been reported infrequently with topical corticosteroids and they may occur more frequently with the use of occlusive dressings and higher potency corticosteroids. These reactions are uled in an approximately decreasing order of occurrence: irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria. Also, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction or discontinuation of potent topical corticosteroid products.

Topically applied Fluticasone Propionate Cream, 0.05% can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS).

Fluticasone Propionate Cream, 0.05% may be used in adult and pediatric patients 3 months of age or older. Safety and efficacy of Fluticasone Propionate Cream, 0.05% in pediatric patients for more than 4 weeks of use have not been established (see PRECAUTIONS: Pediatric Use). The safety and efficacy of Fluticasone Propionate Cream, 0.05% in pediatric patients below 3 months of age have not been established.

Fluticasone Propionate Cream, 0.05% is supplied in:

Store between 2° and 30°C (36° and 86°F).

E. FOUGERA & CO.
a division of Altana Inc.
MELVILLE, NEW YORK 11747

I2332
R3/04
#91