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 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 laboratory tests 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™ 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™ 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™ 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™ Lotion, 0.05% for the minimum amount of time necessary to achieve the desired results (See INDICATIONS AND USAGE).
If irritation develops, CLOBEX™ 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™ Lotion, 0.05% should be discontinued until the infection has been adequately controlled. CLOBEX™ 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. Information for Patients: Patients using topical corticosteroids should receive the following information and instructions:
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This medication is to be used as directed by the physician and should not be used longer than the prescribed time period.
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This medication should not be used for any disorder other than that for which it was prescribed.
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The treated skin area should not be bandaged, otherwise covered, or wrapped so as to be occlusive unless directed by the physician.
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Patients should wash their hands after applying the medication.
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Patients should report any signs of local or systemic adverse reactions to the physician.
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Patients should inform their physicians that they are using CLOBEX™ (clobetasol propionate) Lotion, 0.05% if surgery is contemplated.
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This medication is for external use only. It should not be used on the face, underarms, or groin area, and avoid contact with the eyes and lips.
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As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within 2 weeks, contact the physician.
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Patients should be informed to not use more than 50 g (50 mL or 1.75 fl.oz.) per week of CLOBEX™ Lotion, 0.05%.
Laboratory Tests: The following tests may be helpful in evaluating patients for HPA axis suppression:
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Cosyntropin stimulation test
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AM 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.
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.
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.
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 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.
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 CLOBEX™ (clobetasol propionate) Lotion, 0.05%. Abnormalities seen included cleft palate and skeletal abnormalities.
In rabbits, clobetasol propionate was teratogenic at doses of 3 and 10 µg/kg. These doses are approximately 0.02 and 0.05 times, respectively, the human topical dose of CLOBEX™ (clobetasol propionate) Lotion, 0.05%. Abnormalities seen included cleft palate, cranioschisis, and other skeletal abnormalities.
A teratogenicity study in rats using the dermal route resulted in dose related maternal toxicity and fetal effects from 0.05 to 0.5 mg/kg/day of clobetasol propionate. These doses are approximately 0.14 to 1.4 times, respectively, the human topical dose of CLOBEX™ (clobetasol propionate) Lotion, 0.05%. Abnormalities seen included low fetal weights, umbilical herniation, cleft palate, reduced skeletal ossification, and other skeletal abnormalities.
There are no adequate and well-controlled studies of the teratogenic potential of clobetasol propionate in pregnant women. CLOBEX™ (clobetasol propionate) Lotion, 0.05% 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 breast milk. Because many drugs are excreted in human milk, caution should be exercised when CLOBEX™ Lotion, 0.05% is administered to a nursing woman. Pediatric Use: Use of CLOBEX™ Lotion, 0.05% in pediatric patients is not recommended due to the potential for HPA axis suppression (see PRECAUTIONS: General).
The HPA axis suppression potential of CLOBEX™ 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™ 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™ 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™ 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.
Geriatric Use: Clinical studies of CLOBEX™ (clobetasol propionate) Lotion, 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.
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