Clobetasol Propionate

1 INDICATIONS AND USAGE Clobetasol Propionate Shampoo, 0.05% is a translucent, colorless viscous liquid, supplied in 4 fl. oz. (118 mL) bottles. NDC 63629-9461-01 Storage: Keep bottle tightly closed. Store at USP controlled room temperature 68° to 77°F (20° - 25°C), with excursions permitted between 59° and 86°F (15° - 30°C). Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504 1.1 Indication Clobetasol Propionate Shampoo, 0.05% is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe forms of scalp psoriasis in subjects 18 years of age and older. Treatment should be limited to 4 consecutive 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 Shampoo, 0.05% for the minimum time period necessary to achieve the desired results [see Dosage and Administration (2)] . Use in patients younger than 18 years of age is not recommended due to numerically high rates of hypothalamic-pituitary-adrenal (HPA) axis suppression [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)] . 1.2 Limitations of Use Clobetasol Propionate Shampoo, 0.05% should not be used on the face, groin or axillae. Avoid any contact of the drug product with the eyes and lips. In case of contact, rinse thoroughly with water all parts of the body that came in contact with the shampoo.

1.1 Indication Clobetasol Propionate Shampoo, 0.05% is a super-high potent topical corticosteroid formulation indicated for the treatment of moderate to severe forms of scalp psoriasis in subjects 18 years of age and older. Treatment should be limited to 4 consecutive 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 Shampoo, 0.05% for the minimum time period necessary to achieve the desired results [see Dosage and Administration (2)] . Use in patients younger than 18 years of age is not recommended due to numerically high rates of hypothalamic-pituitary-adrenal (HPA) axis suppression [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)] .

1.2 Limitations of Use Clobetasol Propionate Shampoo, 0.05% should not be used on the face, groin or axillae. Avoid any contact of the drug product with the eyes and lips. In case of contact, rinse thoroughly with water all parts of the body that came in contact with the shampoo.

2 DOSAGE AND ADMINISTRATION Clobetasol propionate shampoo USP, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use. Clobetasol propionate shampoo USP, 0.05%, should be applied onto dry (not wet) scalp once a day in a thin film to the affected areas only, and left in place for 15 minutes before lathering and rinsing. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week. Move the hair away from the scalp so that one of the affected areas is exposed. Position the bottle over the lesion. Apply a small amount of the shampoo directly onto the lesion, letting the product naturally flow from the bottle (gently squeeze the bottle), avoiding any contact of the product with the facial skin, eyes or lips. In case of contact, rinse thoroughly with water. Spread the product so that the entire lesion is covered with a thin uniform film. Massage gently into the lesion and repeat for additional lesion(s). Wash your hands after applying clobetasol propionate shampoo USP, 0.05%. Leave the shampoo in place for 15 minutes, then add water, lather and rinse thoroughly all parts of the scalp and body that came in contact with the shampoo (e.g., hands, face, neck and shoulders). Avoid contact with eyes and lips. Minimize contact to non-affected areas of the body. Although no additional shampoo is necessary to cleanse your hair, you may use a non-medicated shampoo if desired. Treatment should be limited to 4 consecutive weeks. As with other corticosteroids, therapy should be discontinued when control is achieved. If complete disease control is not achieved after 4 weeks of treatment with clobetasol propionate shampoo USP, 0.05%, treatment with a less potent topical steroid may be substituted. If no improvement is seen within 4 weeks, reassessment of the diagnosis may be necessary. Clobetasol propionate shampoo USP, 0.05%, should not be used with occlusive dressings (shower cap or bathing cap) unless directed by a physician. Not for oral, ophthalmic, or intravaginal use. ( 2 ) Clobetasol propionate shampoo USP, 0.05% should be applied onto dry (not wet) scalp once a day in a thin film to the affected areas only, and left in place for 15 minutes before lathering and rinsing. Clobetasol propionate shampoo USP, 0.05% contains a super-high potent topical corticosteroid; therefore treatment should be limited to 4 weeks. ( 2 ) As with other corticosteroids, therapy should be discontinued when control is achieved. ( 2 ) Total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week. ( 2 ) Clobetasol propionate shampoo should not be used with a shower cap or bathing cap. ( 2 )

3 DOSAGE FORMS AND STRENGTHS Shampoo, 0.05%, w/w. Each gram of clobetasol propionate shampoo USP, 0.05%, contains 0.5 mg of clobetasol propionate, USP in a translucent, colorless to pale yellow viscous liquid. Shampoo, 0.05% ( 3 )

4 CONTRAINDICATIONS None None ( 4 )

6 ADVERSE REACTIONS The most common adverse reactions are burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 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 clinical trials with clobetasol propionate shampoo, 0.05%, the following adverse reactions have been reported: headache, burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia. Table 1 summarizes selected adverse reactions that occurred in at least 1% of subjects in the Phase 2 and 3 studies for scalp psoriasis. Table 1: Summary of Selected Adverse Reactions ≥ 1% by Body System Body System Clobetasol Propionate Shampoo, 0.05% N=558 Vehicle Shampoo N=127 Skin and Appendages 49 (8.8%) 28 (22.0%) Discomfort Skin 26 (4.7%) 16 (12.6%) Pruritus 3 (0.5%) 9 (7.1%) Body As A Whole 33 (5.9%) 12 (9.4%) Headache 10 (1.8%) 1 (0.8%) Systemic absorption of topical corticosteroids has produced reversible 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 shampoo, 0.05%. • Endocrine disorders: Cushing’s syndrome, Adrenal suppression • Eye: Eye pain, Vision blurred, Eye irritation • CNS: Dizziness • GI: Nausea • Skin: Erythema, Skin exfoliation, Rash, Skin irritation, Hair color changes, Allergic contact dermatitis, Pain of skin, Skin tightness • Other: Psoriasis (aggravation)

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 clinical trials with clobetasol propionate shampoo, 0.05%, the following adverse reactions have been reported: headache, burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia. Table 1 summarizes selected adverse reactions that occurred in at least 1% of subjects in the Phase 2 and 3 studies for scalp psoriasis. Table 1: Summary of Selected Adverse Reactions ≥ 1% by Body System Body System Clobetasol Propionate Shampoo, 0.05% N=558 Vehicle Shampoo N=127 Skin and Appendages 49 (8.8%) 28 (22.0%) Discomfort Skin 26 (4.7%) 16 (12.6%) Pruritus 3 (0.5%) 9 (7.1%) Body As A Whole 33 (5.9%) 12 (9.4%) Headache 10 (1.8%) 1 (0.8%) Systemic absorption of topical corticosteroids has produced reversible 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 shampoo, 0.05%. • Endocrine disorders: Cushing’s syndrome, Adrenal suppression • Eye: Eye pain, Vision blurred, Eye irritation • CNS: Dizziness • GI: Nausea • Skin: Erythema, Skin exfoliation, Rash, Skin irritation, Hair color changes, Allergic contact dermatitis, Pain of skin, Skin tightness • …

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 shampoo USP, 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 human milk. Because many drugs are excreted in human milk, caution should be exercised when clobetasol propionate shampoo USP, 0.05%, is administered to a nursing woman. 8.4 Pediatric Use Use of clobetasol propionate shampoo USP, 0.05%, in patients under 18 years old is not recommended due to potential for HPA axis suppression [ see Warnings and Precautions ( 5.1 ) ]. The effect of clobetasol propionate shampoo USP, 0.05%, on HPA axis suppression was evaluated in one trial in adolescents 12 to 17 years of age with moderate to severe scalp psoriasis with involvement of at least 25% of the scalp. In this trial, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with clobetasol propionate shampoo USP, 0.05%, applied once daily for 15 minutes to a dry scalp before lathering and rinsing. Only 1 of the 5 subjects who had suppression was tested for recovery of HPA axis, and this subject recovered after 2 weeks. No studies have been performed in patients under the age of 12. Because of a higher ratio of skin surface area to body mass, pediatric patients are at a greater risk than adults of HPA axis suppression and Cushing's syndrome when they are treated with topical corticosteroids. They are therefore also at greater risk of adrenal insufficiency during and/or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children. Therefo …

12.1 Mechanism of Action Like other topical corticosteroids, clobetasol propionate shampoo USP, 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 the 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 shampoo, USP 0.05%, contains clobetasol propionate USP, a synthetic fluorinated corticosteroid, for topical use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents. The chemical name of clobetasol propionate, USP is 21-chloro-9-fluoro-11ß,17-dihydroxy-16ß-methylpregna-1, 4-diene-3, 20-dione 17-propionate. It has the following structural formula: Clobetasol propionate, USP has a molecular weight of 466.97 (CAS Registry Number 25122-46-7). The molecular formula is C 25 H 32 CIFO 5 . Clobetasol propionate, USP is a white to practically white crystalline, odorless powder insoluble in water. Each gram of clobetasol propionate shampoo, USP 0.05%, contains 0.5 mg of clobetasol propionate, USP in a translucent, colorless to pale yellow viscous liquid shampoo base consisting of alcohol 12.08% v/v, citric acid, coco-betaine, polyquaternium-10, purified water, sodium citrate, and sodium laureth sulfate. Structrual Formula

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

16 HOW SUPPLIED/STORAGE AND HANDLING Clobetasol Propionate Shampoo, 0.05% is a translucent, colorless viscous liquid, supplied in 4 fl. oz. (118 mL) bottles. NDC: 72162-1442-2: 118 mL in a BOTTLE Storage: Keep bottle tightly closed. Store at USP controlled room temperature 68° to 77°F (20° - 25°C), with excursions permitted between 59° and 86°F (15° - 30°C). Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504