Clobex Shampoo (Galderma)

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DESCRIPTION

CLOBEX® (clobetasol propionate) Shampoo, 0.05%, contains clobetasol propionate, a synthetic fluorinated corticosteroid, for topical dermatologic use. The corticosteroids constitute a class of primarily synthetic steroids used topically as anti-inflammatory and antipruritic agents.

The chemical name of clobetasol propionate is 21-chloro-9-fluoro-11(beta),17-dihydroxy-16(beta)-methylpregna-1, 4-diene-3, 20-dione 17-propionate. It has the following structural formula:

Clobetasol propionate 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 is a white to practically white crystalline, odorless powder insoluble in water.

Each mL of CLOBEX® (clobetasol propionate) Shampoo, 0.05%, contains clobetasol propionate, 0.05%, in a shampoo base consisting of alcohol, citric acid, coco-betaine, polyquaternium-10, purified water, sodium citrate, and sodium laureth sulfate.

CLINICAL PHARMACOLOGY

Like other topical corticosteroids, CLOBEX® (clobetasol propionate) Shampoo, 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 A2 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 A2.

Pharmacokinetics:    The extent of percutaneous absorption of topical corticosteroids is determined by many factors, including the vehicle, the integrity of the epidermal barrier and occlusion. Topical corticosteroids can be absorbed from normal intact skin, while inflammation and/or other disease processes in the skin may increase percutaneous absorption. Due to the fact that circulating levels of corticosteroids are usually below the limit of detection following application, there are no human data regarding the pharmacokinetics of topical corticosteroids. In such cases pharmacodynamic end points, including both hypothalamic-pituitary-adrenal (HPA) axis testing and topical vasoconstriction, are used as surrogates in the assessments of systemic exposure and relative potency, respectively.

In studies evaluating the potential for hypothalamic-pituitary-adrenal (HPA) axis suppression, use of CLOBEX® (clobetasol propionate) Shampoo, 0.05%, resulted in demonstrable HPA axis suppression in 5 out of 12 (42%) adolescent patients (See PRECAUTIONS ).

CLOBEX® Shampoo is in the super-high range of potency in vasoconstrictor studies.

CLINICAL STUDIES

The safety and efficacy of CLOBEX® (clobetasol propionate) Shampoo, 0.05%, has been evaluated in two clinical trials involving 290 patients with moderate to severe scalp psoriasis. In both trials, patients were treated with either CLOBEX® Shampoo or the corresponding vehicle applied once daily for 15 minutes before lathering and rinsing for a period of 4 weeks. Efficacy results are presented in the table below.

Clinical studies of Clobetasol Propionate Shampoo, 0.05%, did not include sufficient numbers of non-Caucasian patients to determine whether they respond differently than Caucasian patients with regards to efficacy and safety.

INDICATIONS AND USAGE

CLOBEX® (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 (see PRECAUTIONS ). Treatment should be limited to 4 consecutive weeks because of the potential for the drug to suppress the hypothalamic-pituitary-adrenal (HPA) axis. The total dosage should not exceed 50 g (50 mL or 1.75 fl. oz.) per week (see DOSAGE AND ADMINISTRATION ).

Patients should be instructed to use CLOBEX® Shampoo, 0.05%, for the minimum time period necessary to achieve the desired results (see PRECAUTIONS ).

Use in patients younger than 18 years of age is not recommended due to numerically high rates of HPA axis suppression (see PRECAUTIONS , Pediatric Use ).

There were insufficient numbers of non-Caucasian patients to determine whether they responded differently than Caucasian patients with regards to efficacy and safety.

CONTRAINDICATIONS

Use of CLOBEX® (clobetasol propionate) Shampoo, 0.05%, is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

PRECAUTIONS

General:    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 glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing's syndrome, hyperglycemia, and glucosuria can also be produced in some patients by systemic absorption of topical corticosteroids while on treatment.

Conditions which increase systemic absorption include the application of the more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings or use on occluded areas. Therefore, 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. 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 steroid. Recovery of HPA axis function is generally prompt and complete 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.

The effect of CLOBEX® (clobetasol propionate) Shampoo, 0.05% on HPA axis suppression was evaluated in one study in adolescents 12 to 17 years of age. In this study, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with CLOBEX® (clobetasol propionate) Shampoo, 0.05% applied once daily for 15 minutes to a dry scalp before lathering and rinsing.

Pediatric patients may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. (See PRECAUTIONS - Pediatric Use ).

If irritation develops, CLOBEX® Shampoo 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, as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

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 CLOBEX® Shampoo should be discontinued until the infection has been adequately controlled. Although CLOBEX® Shampoo is intended for the topical treatment of moderate to severe scalp psoriasis, it should be noted that certain areas of the body, such as the face, groin, and axillae, are more prone to atrophic changes than other areas of the body following treatment with corticosteroids. CLOBEX® Shampoo 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.

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 and should not be used longer than the prescribed time period. 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 scalp area should not be covered while the medication is on the scalp (e.g., shower cap, bathing cap) so as to be occlusive unless directed by the physician.
4. Patients should report any signs of local or systemic adverse reactions to their physician.
5. As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 4 weeks, contact the physician.
6. Patients should wash their hands after applying the medication.
7. Patients should inform their physician(s) that they are using CLOBEX® Shampoo if surgery is contemplated.
8. Patients should not use more than 50 g (50 mL or 1.75 fl. oz.) per week of CLOBEX® Shampoo.

Laboratory tests:    The cortrosyn stimulation test may be helpful in evaluating patients for HPA axis suppression.

Carcinogenesis, mutagenesis, impairment of fertility: Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.

Clobetasol propionate did not produce any increase in chromosomal aberrations in Chinese hamster ovary cells in vitro in the presence or absence of metabolic activation. Clobetasol propionate was also negative in the micronucleus test in mice after oral administration.

Studies of the effect of CLOBEX® (clobetasol propionate) Shampoo, 0.05% on fertility have not been conducted.

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.

A teratogenicity study of clobetasol propionate in rats using the dermal route resulted in dose related maternal toxicity and fetal effects from 0.05 to 0.5 mg/kg/day. These doses are approximately 0.1 to 1.0 times, respectively, the maximum human topical dose of clobetasol propionate from CLOBEX® Shampoo. Abnormalities seen included low fetal weights, umbilical herniation, cleft palate, reduced skeletal ossification other skeletal abnormalities. Clobetasol propionate administered to rats subcutaneously at a dose of 0.1 mg/kg from day 17 of gestation to day 21 postpartum was associated with prolongation of gestation, decreased number of offspring, increased perinatal mortality of offspring, delayed eye opening and delayed hair appearance in surviving offspring. Some increase in offspring perinatal mortality was also observed at a dose of 0.05 mg/kg. Doses of 0.05 and 0.1 mg/kg are approximately 0.1 and 0.2 fold the maximum human topical dose of clobetasol propionate from CLOBEX® Shampoo.

There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. CLOBEX® Shampoo 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 quanitities in human milk. Because many drugs are excreted in human milk, caution should be exercised when CLOBEX® Shampoo, 0.05%, is administered to a nursing woman.

Pediatric use:    Use of CLOBEX® Shampoo, 0.05%, in patients under 18 years old is not recommended due to potential for HPA axis suppression (see PRECAUTIONS : General ).

The effect of CLOBEX® (clobetasol propionate) Shampoo, 0.05%, on HPA axis suppression was evaluated in one study in adolescents 12 to 17 years of age. In this study, 5 of 12 evaluable subjects developed suppression of their HPA axis following 4 weeks of treatment with CLOBEX® (clobetasol propionate) Shampoo, 0.05%, applied once daily for 15 minutes to a dry scalp before lathering and rinsing. Only one of the five 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.

Therefore, use is not recommended in patients under the age of 18.

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 Shampoo, 0.05%, did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. In general, dose selection for an elderly patient should be made with caution, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

In clinical trials with CLOBEX® Shampoo, the following adverse reactions have been reported: burning/stinging, pruritus, edema, folliculitis, acne, dry skin, irritant dermatitis, alopecia, urticaria, skin atrophy and telangiectasia.

The table below summarizes selected adverse events that occurred in at least 1% of subjects in the Phase 2 and 3 studies for scalp psoriasis.

The following additional local adverse reactions have been reported infrequently with other topical corticosteroids, and they may occur more frequently with the use of occlusive dressings, especially with higher potency corticosteroids. These reactions are listed in an approximately decreasing order of occurrence: hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria.

Systemic absorption of topical corticosteroids has produced reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients.

OVERDOSAGE

Topically applied, CLOBEX® Shampoo can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS ).

DOSAGE AND ADMINISTRATION

CLOBEX® Shampoo 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.

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 CLOBEX® Shampoo. 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 four weeks of treatment with CLOBEX® 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.

CLOBEX® Shampoo should not be used with occlusive dressings unless directed by a physician.

HOW SUPPLIED

CLOBEX® Shampoo is supplied in 4 fl.oz. (118 mL) bottles. NDC 0299-3847-04

Storage:    Keep tightly closed. Store at controlled room temperature 68°F to 77°F (20°C-25°C).

Marketed by:

Galderma Laboratories, L.P.

Fort Worth, Texas 76177 USA

Manufactured by:

DPT Laboratories, Ltd.

San Antonio, Texas 78215 USA

GALDERMA is a registered trademark.

www.clobex.com

325060-0104

Revised: January, 2004

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