Clobetasol Propionate

Important : For use on skin only. Do not get clobetasol propionate lotion near or in your eyes, mouth or vagina.

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 corticosteroid-containing product at the same time may increase the total systemic exposure. Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids. Use in patients under 18 years of age is not recommended due to numerically high rates of HPA axis suppression [see USE IN SPECIFIC POPULATIONS ( 8.4 )]. 5.2 Local Adverse Reactions with Topical Corticosteroids Local adverse reactions may occur more frequently with the use of occlusive dressings and higher potency corticosteroids, including clobetasol propionate. These reactions are listed in an approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae, miliaria, skin atrophy and telangiectasia. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis. 5.3 Allergic Contact Dermatitis Allergic contact dermatitis to any component of topical corticosteroids is usually diagnosed by a failure to heal rather than a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed by patch testing. 5.4 Concomitant Skin Infections In the presence of dermatologic infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, use of clobetasol propionate lotion, 0.05% should be discontinued until the infection has been adequately controlled.

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.

<table ID="ID37" width="100%"><caption>Table 1: Adverse Reactions with Incidence &#x2265; 1% in Clinical Trials </caption><col width="47%"/><col width="53%"/><tbody><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Adverse </content><content styleCode="bold">Reaction</content><content styleCode="bold"> </content></td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule"><content styleCode="bold">Incidence</content><content styleCode="bold"> </content></td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Skin Atrophy </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">4.2% </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Telangiectasia </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">3.2% </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Discomfort Skin </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">1.3% </td></tr><tr><td align="left" valign="top" styleCode=" Lrule Rrule Botrule Toprule">Skin Dry </td><td align="center" valign="top" styleCode=" Lrule Rrule Botrule Toprule">1% </td></tr></tbody></table>