Prescription Drugs

CLINICAL PHARMACOLOGY The corticosteroids are a class of compounds comprising steroid hormones secreted by the adrenal cortex and their synthetic analogs. In pharmacologic doses, corticosteroids are used primarily for their anti-inflammatory and/or immunosuppressive effects. Topical corticosteroids such as clobetasol propionate are effective in the treatment of corticosteroid-responsive dermatoses primarily because of their anti-inflammatory, antipruritic, and vasoconstrictive actions. However, while the physiologic, pharmacologic, and clinical effects of the corticosteroids are well known, the exact mechanisms of their actions in each disease are uncertain. Clobetasol propionate, a corticosteroid, has been shown to have topical (dermatologic) and systemic pharmacologic and metabolic effects characteristic of this class of drugs. Pharmacokinetics The extent of percutaneous absorption of topical corticosteroids, including clobetasol propionate, is determined by many factors, including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings (see DOSAGE AND ADMINISTRATION). As with all topical corticosteroids, clobetasol propionate can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin may increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids (see DOSAGE AND ADMINISTRATION). Once absorbed through the skin, topical corticosteroids enter pharmacokinetic pathways similarly to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids, including clobetasol propionate and its metabolites, are also excreted into the bile. Clobetasol propionate ointment has been shown to depress the plasma levels of adrenal cortical hormones following repeated nonocclusive application to diseased skin in patients with psoriasis and eczematous dermatitis. These effects have been shown to be transient and reversible upon completion of a two-week course of treatment.

Cormax® Ointment 0.05% (clobetasol propionate) Ointment, USP DESCRIPTION Cormax Ointment contains the active compound clobetasol propionate, 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. Chemically, clobetasol propionate is 21-chloro-9-fluoro-11ß,17-dihydroxy- 16ß-methylpregna-1,4-diene-3,20-dione,17-propionate, and it has the following structural formula: Clobetasol propionate has the molecular formula C25H32CIFO5 and a molecular weight of 467. It is a white to cream-colored crystalline powder insoluble in water. Each gram of Cormax Ointment contains 0.5 mg clobetasol propionate in a base composed of propylene glycol, sorbitan sesquioleate, and white petrolatum.

INDICATIONS Cormax Ointment is indicated for short-term treatment of inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses. Treatment beyond two consecutive weeks is not recommended, and the total dosage should not exceed 50 g per week because of the potential for the drug to suppress the hypothalamicpituitary-adrenal (HPA) axis. This product is not recommended for use in pediatric patients under 12 years of age. DOSAGE AND ADMINISTRATION A thin layer of Cormax Ointment should be applied with gentle rubbing to the affected skin area twice daily, once in the morning and once at night. Cormax Ointment is potent; therefore, treatment must be limited to two consecutive weeks, and amounts greater than 50 g per week should not be used. Cormax Ointment is not to be used with occlusive dressings. HOW SUPPLIED Cormax Ointment, 0.05% is supplied in 15 g (NDC 52544-048-86), and 45 g (NDC 52544-048-89) tubes. Store at controlled room temperature 20-25°C (68-77°F). Do not refrigerate. Keep out of reach of children. Manufactured for: Watson Pharmaceuticals, Inc. Corona, CA 92880 USA. Manufactured by: DPT Laboratories, Ltd. San Antonio, TX 78215 USA. Revised: June 2008

OVERDOSE Topically applied Cormax Ointment can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS). CONTRAINDICATIONS Cormax Ointment is contraindicated in patients who are hypersensitive to clobetasol propionate, to other corticosteroids, or to any ingredient in this preparation.

SIDE EFFECTS Cormax Ointment is generally well tolerated when used for two-week treatment periods. The most frequent adverse reactions reported for clobetasol propionate ointment have been local and have included burning sensation, irritation, and itching. These occured in approximately 0.5% of the patients. Less frequent adverse reactions were stinging, cracking, erythema, folliculitis, numbness of fingers, skin atrophy, and telangiectasia, which occurred in approximately 0.3% of the patients. The following local adverse reactions are reported infrequently when topical corticosteroids are used as recommended. These reactions are listed in an approximately decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, 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. In rare instances, treatment (or withdrawal of treatment) of psoriasis with corticosteroids is thought to have exacerbated the disease or provoked the pustular form of the disease, so careful patient supervision is recommended. DRUG INTERACTIONS No information provided.

WARNINGS No information provided. 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 has resulted in reversible HPA axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions that augment systemic absorption include the application of more potent corticosteroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. 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 the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids. Pediatric patients may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity (See PRECAUTIONS: Pediatric Use). If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted. 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, the corticosteroid should be discontinued until the infection has been adequately controlled. 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. Frequent observation of the patient is important if these areas are to be treated. As with other potent topical corticosteroids, Cormax Ointment should not be used in the treatment of rosacea and perioral dermatitis. Topical corticosteroids in general should not be used in the treatment of acne or as sole therapy in widespread plaque psoriasis. Laboratory Tests The following tests may be helpful in evaluating HPA axis suppression: Urinary free cortisol test ACTH stimulation test Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. Studies to determine mutagenicity with prednisolone have revealed negative results. Pregnancy Teratogenic Effects: Pregnancy Category C: The more potent corticosteroids have been shown to be teratogenic in animals after dermal application. Clobetasol propionate has not been tested for teratogenicity by this route; however, it 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. There are no adequate and well-controlled studies of the teratogenic effects of topically applied corticosteroids, including clobetasol, in pregnant women. Therefore, clobetasol and other topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and they should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time. Nursing Mothers It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are prescribed for a nursing woman. Pediatric Use Use of Cormax Ointment in pediatric patients under 12 years of age is not recommended. Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio. HPA axis suppression, Cushing's syndrome, and intracranial hypertension have been reported in pediatric patients receiving topical corticosteroids. Manifestations of adrenal suppression in pediatric patients include linear growth retardation, delayed weight gain, 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 clobetasol propionate scalp application, 0.05% 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.