Clobex Information
Clobex (Clobetasol)
Clobex (Clobetasol) Description
Clobex (Clobetasol) (clobetasol propionate) Lotion, 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.
Clobetasol propionate is 21-chloro-9-fluoro-11β,17-dihydroxy-16β-methylpregna-1,4-diene-3, 20-dione17-propionate, with the empirical formula CHCIFO, a molecular weight of 466.98 (CAS Registry Number 25122-46-7).
The following is the chemical structure:
Clobetasol propionate is a white to practically-white crystalline powder insoluble in water.
Each gram of Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% contains 0.5 mg of clobetasol propionate, in a vehicle base composed of hypromellose, propylene glycol, mineral oil, polyoxyethylene glycol 300 isostearate, carbomer 1342, sodium hydroxide and purified water.
Clobex (Clobetasol) Clinical Pharmacology
Like other topical corticosteroids, Clobex (Clobetasol) (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 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.
Clobex (Clobetasol) Clinical Studies
The efficacy of Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% in psoriasis and atopic dermatitis has been demonstrated in two adequate and well-controlled clinical trials. The first study was conducted in patients with moderate to severe plaque psoriasis. Patients were treated twice daily for 4 weeks with either Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% or vehicle lotion. Study results demonstrated that the efficacy of Clobex (Clobetasol) Lotion, 0.05% in treating moderate to severe plaque psoriasis was superior to that of vehicle.
At the end of treatment (4 weeks), 30 of 82 patients (36.6%) treated with Clobex (Clobetasol) Lotion, 0.05% compared with 0 of 29 (0%) treated with vehicle achieved success. Success was defined as a score of none or very mild (no or very slight clinical signs or symptoms of erythema, plaque elevation, or scaling) on the Global Severity scale of psoriasis.
The second study was conducted in patients with moderate to severe atopic dermatitis. Patients were treated twice daily for 2 weeks with either Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% or vehicle lotion. Study results demonstrated that the efficacy of Clobex (Clobetasol) Lotion, 0.05% in treating moderate to severe atopic dermatitis was superior to that of vehicle.
At the end of treatment (2 weeks), 41 of 96 patients (42.7%) treated with Clobex (Clobetasol) Lotion, 0.05% compared with 4 of 33 (12.1%) treated with vehicle achieved success. Success was defined as a score of none or very mild (no or very slight clinical signs or symptoms of erythema, induration/papulation, oozing/crusting, or pruritus) on the Global Severity scale of atopic dermatitis.
Clobex (Clobetasol) Indications And Usage
Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% is a super-high potent 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 (see ). Treatment should be limited to 2 consecutive weeks. The total dosage should not exceed 50 g (50 mL or 1.75 fl.oz.) per week.
For the treatment of moderate to severe plaque psoriasis, localized lesions (less than 10% body surface area) that have not sufficiently improved after the initial 2-week treatment with Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% may be treated for up to 2 additional weeks. Any additional benefits of extending treatment should be weighed against the risk of HPA axis suppression before prescribing for more than 2 weeks.
Patients should be instructed to use Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% for the minimum amount of time necessary to achieve the desired results (see ).
Use in patients younger than 18 years of age is not recommended due to numerically high rates of HPA axis suppression (see ).
Clobex (Clobetasol) Contraindications
Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.
Clobex (Clobetasol) Precautions
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 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 steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients applying a topical steroid to a large surface area or to areas under occlusion should be evaluated periodically for evidence of adrenal suppression (see below). If adrenal 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 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) Lotion, 0.05% on HPA axis function was compared to clobetasol propionate cream 0.05% (Temovate E® Emollient, 0.05%) in adults in two studies, one for psoriasis and one for atopic dermatitis. In total, 8 of 10 evaluable patients with moderate to severe plaque psoriasis experienced adrenal suppression following 4 weeks of Clobex (Clobetasol) 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 patients remained suppressed after 8 days. In this comparative study, for clobetasol propionate cream, 0.05% there were 3 of 10 evaluable patients with HPA axis suppression. Furthermore, 5 of 9 evaluable patients with moderate to severe atopic dermatitis experienced adrenal suppression following 2 weeks of Clobex (Clobetasol) Lotion, 0.05% therapy (treatment beyond 2 consecutive weeks is not recommended in moderate to severe atopic dermatitis). Of the 3 patients that had follow-up testing, one patient failed to recover adrenal function 7 days post-treatment. For patients treated with clobetasol propionate cream, 0.05%, 4 of 9 evaluable patients experienced adrenal suppression following 2 weeks of treatment. Of the 2 patients 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 studies.
The potential increase in systemic exposure does not correlate with any proven benefit, but may lead to an increased potential for hypothalamic-pituitary-adrenal (HPA) axis suppression. Patients with acute illness or injury may have increased morbidity and mortality with intermittent HPA axis suppression. Patients should be instructed to use Clobex (Clobetasol) Lotion, 0.05% for the minimum amount of time necessary to achieve the desired results (See ).
If irritation develops, Clobex (Clobetasol) Lotion, 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, as with most topical products not containing corticosteroids.
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 (Clobetasol) Lotion, 0.05% should be discontinued until the infection has been adequately controlled.
Clobex (Clobetasol) Lotion, 0.05% should not be used in the treatment of rosacea or perioral dermatitis, and should not be used on the face, groin, or axillae.
Clobex (Clobetasol) Laboratory Tests
The following tests may be helpful in evaluating patients for HPA axis suppression:
Long-term animal studies have not been performed to evaluate the carcinogenic potential of clobetasol propionate.
Clobetasol propionate was non-mutagenic in three different test systems: the Ames test, the gene conversion assay, and the B WP2 fluctuation test.
Studies in the rat following subcutaneous administration at dosage levels up to 50 μg/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.
Use of Clobex (Clobetasol) Lotion, 0.05% in pediatric patients is not recommended due to the potential for HPA axis suppression (see ).
The HPA axis suppression potential of Clobex (Clobetasol) 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 patients were evaluated for HPA axis function. Patients were treated twice daily for 2 weeks with Clobex (Clobetasol) Lotion, 0.05%. After 2 weeks of treatment, 9 out of 14 of the patients experienced adrenal suppression. One out of 4 patients treated with Clobex (Clobetasol) Lotion, 0.05% who were retested remained suppressed two weeks post-treatment. In comparison, 2 of 10 of the patients treated with clobetasol propionate cream, 0.05% demonstrated HPA axis suppression. One patient who was retested recovered.
None of the patients 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 Clobex (Clobetasol) Lotion, 0.05%. However patients with acute illness or injury may have increased morbidity and mortality with intermittent HPA axis suppression.
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 glucocorticosteroid 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.
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 absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.
In controlled clinical trials with Clobex (Clobetasol) (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 Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% at 1.0% or greater was:
Other local adverse events occurred at rates less than 1.0%. Similar rates of local adverse reactions were reported in the comparator (clobetasol propionate cream, 0.05%). Most local adverse events were rated as mild to moderate and they are not affected by age, race or gender.
The following additional local adverse reactions have been reported with topical corticosteroids. They 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: irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, striae and miliaria.
Clobex (Clobetasol) Overdosage
Topically applied Clobex (Clobetasol) (clobetasol propionate) Lotion, 0.05% can be absorbed in sufficient amount to produce systemic effects. (See ).
Clobex (Clobetasol) Dosage And Administration
Clobex (Clobetasol) Lotion, 0.05% should be applied to the affected skin areas twice daily and rubbed in gently and completely. (See .)
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.
Therapy should be discontinued when control has been achieved. If no improvement is seen within 2 weeks, reassessment of diagnosis may be necessary.
Use in pediatric patients younger than 18 years is not recommended because of numerically high rates of HPA axis suppression (See ).
Unless directed by physician, Clobex (Clobetasol) Lotion, 0.05% should not be used with occlusive dressings.
Clobex (Clobetasol) How Supplied
Clobex (Clobetasol) Lotion, 0.05% is supplied in the following sizes:
2 fl. oz./59 mL NDC 0299-3848-02 high density polyethylene bottles.
4 fl. oz./118 mL NDC 0299-3848-04 high density polyethylene bottles.
Store at controlled room temperature 68˚ to 77˚F (20˚-25˚C). Protect from freezing.
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.
Temovate E is a registered trademark of Glaxo SmithKline.
325067-1004
Revised: October 2004
Clobex (Clobetasol)
Clobex (Clobetasol) Package Label
Clobex (Clobetasol) (clobetasol propionate)
GALDERMA
For external use only. Not for eye use.
Store at controlled room temperature 68° to 77°F (20° - 25°C). Protect from freezing. See lot no. and expiration date on bottom of bottle.
US Patent No. 6,106,848
Marketed by:GALDERMA LABORTORIES, L.P.Fort Worth, Texax 76177 USA
Manufactured by:DPT Laboratories, Ltd.San Antonio, Texas 78215 USA
GALDERMA is a registered trademark.
326197-0406
