CLOBETASOL: 7,806 Adverse Event Reports & Safety Profile

Clobetasol Propionate Emulsion Foam, 0.05% is a white to off-white emulsion aerosol foam containing the active ingredient clobetasol propionate, USP, a synthetic corticosteroid for topical dermatologic use. Clobetasol, an analog of prednisolone, has a high degree of glucocorticoid activity and a slight degree of mineralocorticoid activity. Clobetasol propionate, USP 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 ClFO 5 , and a molecular weight of 467 g/mol. The following is the chemical structure: Clobetasol Propionate, USP Clobetasol propionate, USP is a white to almost white crystalline powder, practically insoluble in water, slightly soluble in benzene and diethyl ether; sparingly soluble in ethanol; freely soluble in acetone, in dimethylsulfoxide, in chloroform, in methanol and in dioxane. Each gram of Clobetasol Propionate Emulsion Foam, 0.05% contains 0.5 mg clobetasol propionate, USP. The foam also contains anhydrous citric acid, cetyl alcohol, cyclomethicone, isopropyl myristate, light mineral oil, polyoxyl-20 cetostearyl ether, potassium citrate, propylene glycol, purified water, sorbitan monolaurate, white petrolatum, and phenoxyethanol as a preservative.

Clobetasol Propionate Emulsion

Foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/butane) propellant. structure

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 <span class="opacity-50 text-xs">[see Dosage and Administration (2)]</span> . Use in patients younger than 18 years of age is not recommended due to numerically high rates of hypothalamic-pituitary-adrenal (HPA) axis suppression <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)]</span> .

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 <span class="opacity-50 text-xs">[see Dosage and Administration (2)]</span> . Use in patients younger than 18 years of age is not recommended due to numerically high rates of hypothalamic-pituitary-adrenal (HPA) axis suppression <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)]</span> .

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.

AND ADMINISTRATION Clodan ® (clobetasol propionate) Shampoo, 0.05% is for topical use only, and not for ophthalmic, oral or intravaginal use. Clodan ® (clobetasol propionate) Shampoo, 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 Clodan ® (clobetasol propionate) Shampoo, 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 Clodan ® (clobetasol propionate) Shampoo, 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. Clodan ® (clobetasol propionate) Shampoo, 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 ) Clodan ® (clobetasol propionate) Shampoo, 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. Clodan ® (clobetasol propionate) Shampoo, 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 ) Clodan ® (clobetasol propionate) Shampoo, 0.05% should not be used with a shower cap or bathing cap. ( 2 )

BYQLOVI is contraindicated in most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. BYQLOVI is contraindicated in most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. ( 4 )

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
• Other: Psoriasis (aggravation)

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 ) If irritation develops in the presence of dermatological 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 Shampoo, 0.05% should be discontinued until the infection has been adequately controlled. ( 5.3 ) 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. ( 5.4 )

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 can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. The effect of clobetasol propionate shampoo, 0.05% on HPA axis suppression was evaluated in one trial in adolescents 12 to 17 years of age. In this trial, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with clobetasol propionate shampoo, 0.05% applied once daily for 15 minutes to a dry scalp before lathering and rinsing. 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 equivalent doses due to their larger skin surface to body mass ratios <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.4 )]</span> .

5.2 Allergic Contact Dermatitis If irritation develops, Clobetasol Propionate Shampoo, 0.05% should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed with patch testing.

5.3 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 Shampoo, 0.05% should be discontinued until the infection has been adequately controlled.

5.4 Local Adverse Reactions with Topical Corticosteroids Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis.

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 can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid. The effect of clobetasol propionate shampoo, 0.05% on HPA axis suppression was evaluated in one trial in adolescents 12 to 17 years of age. In this trial, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with clobetasol propionate shampoo, 0.05% applied once daily for 15 minutes to a dry scalp before lathering and rinsing. 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 equivalent doses due to their larger skin surface to body mass ratios <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.4 )]</span> .

5.2 Allergic Contact Dermatitis If irritation develops, Clobetasol Propionate Shampoo, 0.05% should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing a failure to heal rather than noting a clinical exacerbation. Clinical diagnosis of allergic contact dermatitis can be confirmed with patch testing.

5.3 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 Shampoo, 0.05% should be discontinued until the infection has been adequately controlled.

5.4 Local Adverse Reactions with Topical Corticosteroids Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible. Clobetasol propionate is not recommended in patients with acne vulgaris, rosacea or perioral dermatitis.

PRECAUTIONS: General: Clobetasol propionate is a highly potent topical corticosteroid that has been shown to suppress the HPA axis at doses as low as 2 g per day. Systemic absorption of topical corticosteroids can produce reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal from treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on therapy. Patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of HPA axis suppression. This may be done by using the ACTH stimulation, A.M. plasma cortisol, and urinary free cortisol tests. Patients receiving superpotent corticosteroids should not be treated for more than 2 weeks at a time and only small areas should be treated at any one time due to the increased risk of HPA suppression. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt upon discontinuation of topical corticosteroids. Infrequently, signs and symptoms of glucocorticosteroid insufficiency may occur requiring supplemental systemic corticosteroids. For information on systemic supplementation, see prescribing information for those products. Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios (see Error! Hyperlink reference not valid. ). If irritation develops, clobetasol propionate should be discontinued and appropriate therapy instituted. Allergic contact dermatitis with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing. If concomitant skin infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of clobetasol propionate should be discontinued until the infection has been adequately controlled. Clobetasol propionate gel, cream and ointment should not be used in the treatment of rosacea or perioral dermatitis and it should not be used on the face, groin, or axillae. Information for Patients: Patients using topical corticosteroids should receive the following information and instructions: 1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes. 2. This medication should not be used for any disorder other than that for which it was prescribed. 3. The treated skin area should not be bandaged, otherwise covered or wrapped, so as to be occlusive unless directed by the physician. 4. Patients should report any signs of local adverse reactions to the physician. 5. Patients should inform their physicians that they are using clobetasol propionate if surgery is contemplated.

Laboratory

Tests: The following tests may be helpful in evaluating patients for HPA axis suppression: ACTH stimulation test, A.M. plasma cortisol test, Urinary free cortisol test. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate. Studies in the rat following subcutaneous administration at dosage levels up to 50 mcg/kg per day revealed that the females exhibited an increase in the number of resorbed embryos and a decrease in the number of living fetuses at the highest dose. Clobetasol propionate was non-mutagenic in three different test systems: the Ames test, the Saccharomyces cerevisiae gene conversion assay, and the E. coli B WP2 fluctuation test. Pregnancy: Teratogenic Effects– Pregnancy Category C. 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 has not been tested for teratogenicity when applied topically; however, it is absorbed percutaneously, and when administered subcutaneously it was a significant teratogen in both the rabbit and mouse. Clobetasol propionate has greater teratogenic potential than steroids that are less potent. Teratogenicity studies in mice using the subcutaneous route resulted in fetotoxicity at the highest dose tested (1 mg/kg) and teratogenicity at all dose levels tested down to 0.03 mg/kg. These doses are approximately 1.4 and 0.04 times, respectively, the human topical dose of clobetasol propionate gel, cream and ointment. Abnormalities seen included cleft palate and skeletal abnormalities. In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 mcg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of clobetasol propionate gel, cream and ointment. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities. There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. Clobetasol propionate gel, cream and ointment should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 either clobetasol propionate gel, cream and ointment is administered to a nursing woman.

Pediatric

Use: Safety and effectiveness of clobetasol propionate gel, cream and ointment in pediatric patients have not been established. Use in children under 12 years of age is not recommended. 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 or after withdrawal of treatment. Adverse effects including striae have been reported with inappropriate use of topical corticosteroids in infants and children (see PRECAUTIONS ). HPA axis suppression, Cushing's syndrome, linear growth retardation, delayed weight gain and intracranial hypertension have been reported in children receiving topical corticosteroids. Manifestations of adrenal suppression in children include low plasma cortisol levels, and an absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Geriatric

Use: Clinical studies of clobetasol propionate drug products in US clinical trials did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious.

Active Ingredients: Ketoconazole 15mg Clobetasol Propionate 0.25mg

Clobetasol propionate 0.25mg