Betamethasone Dipropionate

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria in some patients.

Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings. Use of more than one corticosteroid-containing product at the same time may increase total systemic glucocorticoid exposure. (See DOSAGE AND ADMINISTRATION.)

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. In an open-label pediatric study of 53 evaluable patients, of the 15 patients who showed evidence of suppression, 2 patients were tested 2 weeks after discontinuation of Betamethasone Dipropionate Ointment, and both patients showed recovery of HPA axis function. 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 dermatological 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.

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 intended effects.

Patients using topical corticosteroids should receive the following information and instructions:

1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.

2. Patients should be advised not to use this medication for any disorder other than that for which it was prescribed.

3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive. (See DOSAGE AND ADMINISTRATION.)

4. Patients should report any signs of local adverse reactions.

5. Other corticosteroid-containing products should not be used with Betamethasone Dipropionate Ointment without first talking to your physician.

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

Urinary-free cortisol test

ACTH stimulation test

Long-term animal studies have not been performed to evaluate the carcinogenic potential of betamethasone dipropionate.

Betamethasone was negative in the bacterial mutagenicity assay (Salmonella typhimurium and Escherichia coli), and in the mammalian cell mutagenicity assay (CHO/HGPRT). It was positive in the in-vitro human lymphocyte chromosome aberration assay, and equivocal in the in-vivo mouse bone marrow micronucleus assay. This pattern of response is similar to that of dexamethasone and hydrocortisone.

Reproductive studies with betamethasone dipropionate carried out in rabbits at doses of 1.0 mg/kg by the intramuscular route and in mice up to 33 mg/kg by the intramuscular route indicated no impairment of fertility except for dose-related increases in fetal resorption rates in both species. These doses are approximately 0.5 and 4 fold the estimated maximum human dose based on a mg/m² comparison, respectively.

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.

Betamethasone Dipropionate Ointment is not recommended in pediatric patients 12 years of age and younger. (See CLINICAL PHARMACOLOGYand ADVERSE REACTIONSSections.)

In an open-label study, 15 of 53 (28%) evaluable pediatric patients (aged 6 months – 12 years old) using Betamethasone Dipropionate Ointment for treatment of atopic dermatitis demonstrated HPA axis suppression. The proportion of patients with adrenal suppression in this study was progressively greater, the younger the age group. (See CLINICAL PHARMACOLOGY – Pharmacokinetics.)

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. The study described above supports this premise as adrenal suppression in 9-12 year olds, 6-8 year olds, 2-5 year olds, and 3 months – 1 year old was 17%, 27%, 29%, and 36%, respectively.

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.

Administration of topical corticosteroids to pediatric patients should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of pediatric patients.