Clobetasol Propionate

1 INDICATIONS AND USAGE Clobetasol propionate lotion, 0.05% is a corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, in patients 18 years of age or older ( 1.1 ). Limitations of Use: Do not use on the face, axillae or groin. ( 1.2 ) Do not use if atrophy is present at the treatment site. ( 1.2 ) Do not use for rosacea or perioral dermatitis. ( 1.2 ) 1.1 Indication Clobetasol propionate lotion, 0.05% is a super-high potent topical corticosteroid formulation indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses only in patients 18 years of age or older. Treatment should be limited to 2 consecutive weeks. For moderate to severe plaque psoriasis, treatment may be extended for an additional 2 weeks for localized lesions (less than 10% body surface area) that have not sufficiently improved after the initial 2-week treatment. Any additional benefits of extending treatment should be weighed against the risk of hypothalamic-pituitary-adrenal (HPA) axis suppression before prescribing for more than 2 weeks. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz) per week. Patients should be instructed to use clobetasol propionate lotion, 0.05% for the minimum amount of time necessary to achieve the desired results [see DOSAGE AND ADMINISTRATION ( 2 )]. Use in patients under 18 years of age is not recommended due to numerically high rates of HPA axis suppression [see WARNINGS AND PRECAUTIONS ( 5.1 ) and USE IN SPECIFIC POPULATIONS ( 8.4 )]. 1.2 Limitations of Use Clobetasol propionate lotion, 0.05% should not be used on the face, axillae, or groin and should not be used if there is atrophy at the treatment site. Clobetasol propionate lotion, 0.05% should not be used in the treatment of rosacea or perioral dermatitis.

2 DOSAGE AND ADMINISTRATION Clobetasol propionate lotion, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use. Clobetasol propionate lotion, 0.05% should be applied to the affected skin areas twice daily and rubbed in gently and completely. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. Clobetasol propionate lotion, 0.05% contains a topical corticosteroid; therefore treatment should be limited to 2 consecutive weeks for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and up to 2 additional weeks in localized lesions (less than 10% body surface area) of moderate to severe plaque psoriasis that have not sufficiently improved after the initial 2 weeks of treatment with clobetasol propionate lotion, 0.05%. Unless directed by physician, clobetasol propionate lotion, 0.05% should not be used with occlusive dressings. Not for oral, ophthalmic, or intravaginal use. ( 2 ) Clobetasol propionate lotion, 0.05% should be applied directly onto the affected skin areas twice daily and rubbed in gently. ( 2 ) Clobetasol propionate lotion, 0.05% contains a super-high potent topical corticosteroid; therefore treatment should be limited to 2 weeks. For moderate to severe plaque psoriasis, treatment may be extended for additional 2 weeks for localized lesions (<10% body surface area) that have not sufficiently improved. ( 2 ) Total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week. ( 2 )

5 WARNINGS AND PRECAUTIONS Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the hypothalamic-pituitary- adrenal (HPA) axis at the lowest doses tested. ( 5.1 ) Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. ( 5.1 ) Systemic absorption may require periodic evaluation for HPA axis suppression. Modify use if HPA axis suppression develops. ( 5.1 ) Children may be more susceptible to systemic toxicity from use of topical corticosteroids. ( 5.1 , 8.4 ) Local adverse reactions with topical corticosteroids may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions include: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria. ( 5.2 ) 5.1 Effects on the Endocrine System Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at the lowest doses tested. Systemic absorption of topical corticosteroids has caused reversible adrenal suppression with the potential for clinical glucocorticosteroid insufficiency after withdrawal of treatment. This may occur during treatment or upon withdrawal of the topical corticosteroid. The effect of clobetasol propionate lotion, 0.05% on HPA axis function was compared to clobetasol propionate cream 0.05% (Temovate E ® Emollient, 0.05%) in adults in two trials, one for psoriasis and one for atopic dermatitis. In total, 8 of 10 evaluable subjects with moderate to severe plaque psoriasis experienced adrenal suppression following 4 weeks of clobetasol propionate lotion, 0.05% therapy (treatment beyond 4 consecutive weeks is not recommended in moderate to severe plaque psoriasis). In follow- up testing, 1 of 2 subjects remained suppressed after 8 days. In this comparative trial, for clobetasol propionate cream, 0.05% there were 3 of 10 evaluable subjects with HPA axis suppression. Furthermore, 5 of 9 evaluable subjects with moderate to severe atopic dermatitis experienced adrenal suppression following 2 weeks of clobetasol propionate lotion, 0.05% therapy (treatment beyond 2 consecutive weeks is not recommended in moderate to severe atopic dermatitis). Of the 3 subjects that had follow-up testing, one subjects failed to recover adrenal function 7 days post-treatment. For subjects treated with clobetasol propionate cream, 0.05%, 4 of 9 evaluable subjects experienced adrenal suppression following 2 weeks of treatment. Of the 2 subjects that had follow-up testing, both recovered adrenal function 7 days post-treatment. The proportion of subjects suppressed may be underestimated because the adrenal glands were stimulated weekly with cosyntropin in these trials. Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure. An adrenocorticotropic hormone (ACTH) stimulation test may be helpful in evaluating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids. Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids. Use of more than one …

4 CONTRAINDICATIONS None None ( 4 )

8.1 Pregnancy Teratogenic Effects: Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Therefore, clobetasol propionate lotion, 0.05% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Some corticosteroids have been shown to be teratogenic after dermal application to laboratory animals. Clobetasol propionate is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and the mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent. The effect of clobetasol propionate on pregnancy outcome and development of offspring was studied in the rat. Clobetasol propionate was administered subcutaneously to female rats twice daily (0, 12.5, 25, and 50 mcg/kg/day) from day 7 of presumed gestation through day 25 of lactation or day 24 presumed gestation for those rats that did not deliver a litter. The maternal no-observed-effect level (NOEL) for clobetasol propionate was less than 12.5 mcg/kg/day due to reduced body weight gain and feed consumption during the gestation period. The reproductive NOEL in the dams was 25 mcg/kg/day (ratio of animal dose to proposed human dose of 0.07 on a mg/m 2 /day basis) based on prolonged delivery at a higher dose level. The no-observed-adverse-effect-level (NOAEL) for viability and growth in the offspring was 12.5 mcg/kg/day (ratio of animal dose to proposed human dose of 0.03 on a mg/m 2 /day basis) based on incidence of stillbirths, reductions in pup body weights on days 1 and 7 of lactation, increased pup mortality, increases in the incidence of umbilical hernia, and increases in the incidence of pups with cysts on the kidney at higher dose levels during the preweaning period. The weights of the epididymides and testes were significantly reduced at higher dosages. Despite these changes, there were no effects on the mating and fertility of the offspring.

8.3 Nursing Mothers Systemically administered corticosteroids appear in human milk and could 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 breast milk. Because many drugs are excreted in human milk, caution should be exercised when clobetasol propionate lotion, 0.05% is administered to a nursing woman.

6 ADVERSE REACTIONS The most common adverse reactions (incidence > 1%) are skin atrophy, telangiectasia, discomfort skin and skin dry ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 1-800-399-2561 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 with clobetasol propionate lotion, 0.05%, the following adverse reactions have been reported: burning/stinging, skin dryness, irritation, erythema, folliculitis, pruritus, skin atrophy, and telangiectasia. The pooled incidence of local adverse reactions in trials for psoriasis and atopic dermatitis with clobetasol propionate lotion, 0.05% at 1% or greater was: Table 1: Adverse Reactions with Incidence ≥ 1% in Clinical Trials Adverse Reaction Incidence Skin Atrophy 4.2% Telangiectasia 3.2% Discomfort Skin 1.3% Skin Dry 1% Most local adverse events were rated as mild to moderate and they are not affected by age, race or gender. Systemic absorption of topical corticosteroids has produced hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. 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 adverse reactions have been identified during post-approval use of clobetasol propionate lotion, 0.05%. Endocrine disorders : Cushing's syndrome, Adrenal suppression Skin : Rash, Pain of skin, Skin exfoliation, Skin chapped, Scaling, Induration/papulation, Lichenification. Other : Psoriasis (aggravation), Plaque elevation, Excoriation.