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 )

3 DOSAGE FORMS AND STRENGTHS Lotion, 0.05% w/w; Each gram of Clobetasol Propionate Lotion, 0.05% contains 0.5 mg of clobetasol propionate, USP in a white liquid. ( 3 ) Lotion, 0.05% w/w; Each gram of Clobetasol Propionate Lotion, 0.05% contains 0.5 mg of clobetasol propionate, USP in a white liquid. ( 3 )

4 CONTRAINDICATIONS None None. ( 4 )

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.

8 USE IN SPECIFIC POPULATIONS 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. 8.4 Pediatric Use Use of clobetasol propionate lotion, 0.05% in pediatric patients is not recommended due to the potential for HPA axis suppression [ see Warnings and Precautions ( 5.1 ) ]. The HPA axis suppression potential of clobetasol propionate lotion, 0.05% has been studied in adolescents (12 to 17 years of age) with moderate to severe atopic dermatitis covering a minimum of 20% of the total body surface area. In total 14 subjects were evaluated for HPA axis function. Subjects were treated twice daily for 2 weeks with clobetasol propionate lotion, 0.05%. After 2 weeks of treatment, 9 out of 14 of the subjects experienced adrenal suppression. One out of 4 subjects treated with clobetasol propionate lotion, 0.05% who were retested remained suppressed two weeks post-treatment. In comparison, 2 of 10 subjects treated with clobetasol propionate cream, 0.05% demonstrated HPA axis suppression. One subject who was retested recovered. None of the subjects who developed HPA axis suppression had concomitant clinical signs of adrenal suppression and none of them was discontinued from the study for reasons related to the safety or tolerability of clobetasol propionate lotion, 0.05%. However patients with acute illness or injury may have increased morbidity and mortality with intermittent HPA axis suppression. Be …

12.1 Mechanism of Action Like other topical corticosteroids clobetasol propionate lotion, 0.05% 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 induction of phospholipase A 2 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 A 2 .

11 DESCRIPTION Clobetasol propionate lotion, 0.05% contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. Clobetasol propionate is 21-chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17-propionate, with the empirical formula C 25 H 32 CIFO 5 , and a molecular weight of 466.97 (CAS Registry Number 25122-46-7). The following is the chemical structure: Clobetasol propionate, USP is a white to cream crystalline powder. It is soluble in acetone, in dimethyl sulfoxide, in chloroform, in methanol, and in dioxane; sparingly soluble in ethanol; slightly soluble in benzene and in diethyl ether; practically insoluble in water. Each gram of clobetasol propionate lotion, 0.05% contains 0.5 mg of clobetasol propionate, in a vehicle base contains following inactive ingredients: cetostearyl alcohol, glycerol monostearate and polyethylene glycol-75 palmitostearate, glyceryl stearate/polyethylene glycol-100 stearate, mineral oil, polyoxyethylene glycol 300 isostearate, propylene glycol and purified water. Image

10 OVERDOSAGE Topically applied clobetasol propionate lotion, 0.05% can be absorbed in sufficient amount to produce systemic effects [ see Warnings and Precautions ( 5.1 ) ].

16 HOW SUPPLIED/STORAGE AND HANDLING Clobetasol Propionate Lotion, 0.05% is a white to off-white opaque lotion supplied in the following sizes: 2 fl.oz./59 mL, NDC 72578-085-01 high density polyethylene bottles. 4 fl.oz./118 mL, NDC 72578-085-02 high density polyethylene bottles. Store at USP controlled room temperature 68°F to 77°F (20°C to 25°C), with excursions permitted between 59°F and 86°F (15°C to 30°C). Protect from freezing.