Pharmacokinetics

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle and the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids can be absorbed through 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.

Once absorbed through the skin, topical corticosteroids enter pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees, are metabolized primarily in the liver and excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

Pharmacokinetic studies in men with Desoximetasone Cream USP, 0.25% with tagged desoximetasone showed a total of 5.2% ± 2.9% excretion in urine (4.1% ± 2.3%) and feces (1.1% ± 0.6%) and no detectable level (limit of sensitivity: 0.005 µg/mL) in the blood when it was applied topically on the back followed by occlusion for 24 hours. Seven days after application, no further radioactivity was detected in urine or feces. The half-life of the material was 15 ± 2 hours (for urine) and 17 ± 2 hours (for feces) between the third and fifth trial day. Studies with other similarly structured steroids have shown that predominant metabolite reaction occurs through conjugation to form the glucuronide and sulfate ester. Studies performed with Desoximetasone Cream USP, 0.05%; Desoximetasone Cream USP, 0.25% and Desoximetasone Gel USP, 0.05% indicate that they are in the high range of potency as compared with other topical corticosteroids.

General

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. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure. (See DOSAGE AND ADMINISTRATION section.)

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 ACTH stimulation and urinary free cortisol 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 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 PRECAUTIONS – Pediatric Use.)

If irritation develops, Desoximetasone Cream USP, 0.05%; Desoximetasone Cream USP, 0.25% or Desoximetasone Gel USP, 0.05% 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 Desoximetasone Cream USP, 0.05%; Desoximetasone Cream USP, 0.25% or Desoximetasone Gel USP, 0.05% should be discontinued until the infection has been adequately controlled.

This medication should not be used on the face, underarm or groin area.

As with other corticosteroids, therapy should be discontinued when control is achieved. If no improvement is seen within two weeks, the diagnosis and therapy should be re-evaluated.

Information for the Patient

Patients using topical corticosteroids should receive the following information and instructions. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or unintended effects:

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 to their physician any signs of local adverse reactions.
5. Other topical corticosteroid-containing products should not be used with Desoximetasone Cream USP, 0.05% or Desoximetasone Cream USP, 0.25% or Desoximetasone Gel USP, 0.05% without first talking to your physician.
6. If no improvement is seen in 2 weeks, contact your physician.

Laboratory Tests

The following tests may be helpful in evaluating patients for HPA axis suppression:

 

ACTH stimulation test

 

Urinary free cortisol test

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of desoximetasone.

Desoximetasone was nonmutagenic in the Ames test.

Pregnancy

Nursing Mothers

It is not known whether topical administration of corticosteroids can 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, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than adult patients because of a larger skin surface area to body weight ratio.

Hypothalamic-pituitary-adrenal (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. Chronic corticosteroid therapy may interfere with linear bone growth in pediatric patients.

Geriatric Use

Clinical studies of Desoximetasone Cream USP, 0.05%; Desoximetasone Cream USP, 0.25% and Desoximetasone Gel USP, 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 generally, dose selection for an elderly patient should be cautious.

Store at 20° - 25°C (68° - 77°F) [see USP Controlled Room Temperature].