5.1 Effects on Calcium Metabolism

Hypercalcemia and hypercalciuria have been reported with use of Calcipotriene 0.005% and Betamethasone Dipropionate 0.064%. If hypercalcemia or hypercalciuria develop, treatment should be discontinued until parameters of calcium metabolism have normalized. In the trials that included assessment of the effects of Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Ointment on calcium metabolism, such testing was done after 4 weeks of treatment. The effects of Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Ointment on calcium metabolism following treatment durations of longer than 4 weeks have not been eva luated.

5.2 Effects on Endocrine System

Systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for clinical glucocorticosteroid insufficiency. This may occur during treatment or upon withdrawal of the topical corticosteroid.

HPA axis suppression has been observed with Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Ointment [see Clinical Pharmacology (12.2)]. The effects of Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Ointment on the HPA axis following treatment durations of longer than 4 weeks have not been adequately studied.

In a study of 32 subjects concomitantly treated with Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Scalp Topical Suspension on the scalp and Calcipotriene 0.005% and Betamethasone Dipropionate 0.064% Ointment on the body, adrenal suppression was identified in 5 of 32 subjects (15.6%) after 4 weeks of treatment [see CLINICAL PHARMACOLOGY Pharmacodynamics (12.2)].

Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically eva luated for HPA axis suppression. Factors that predispose a patient using a topical corticosteroid to HPA axis suppression include the use of more potent steroids, use over large surface areas, use over prolonged periods, use under occlusion, use on an altered skin barrier, and use in patients with liver failure.

An ACTH stimulation test may be helpful in eva luating patients for HPA axis suppression. If HPA axis suppression is documented, an attempt should be made to gradually withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid. Manifestations of adrenal insufficiency may require supplemental systemic corticosteroids. Recovery of HPA axis function is generally prompt and complete upon discontinuation of topical corticosteroids.

Cushing's syndrome, hyperglycemia, and unmasking of latent diabetes mellitus can also result from systemic absorption of topical corticosteroids.

Use of more than one corticosteroid-containing product at the same time may increase the total systemic corticosteroid exposure.

Pediatric patients may be more susceptible to systemic toxicity from use of topical corticosteroids [see Use in Specific Populations (8.4)].

5.3 Local Adverse Reactions with Topical Corticosteroids

Local adverse reactions may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria. Some local adverse reactions may be irreversible.