Vasoconstriction:

In a vasoconstrictor trial in healthy subjects, the skin blanching response of calcipotriene and betamethasone dipropionate ointment was consistent with that of a potent corticosteroid when compared with other topical corticosteroids. However, similar blanching scores do not necessarily imply therapeutic equivalence.

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression:

HPA axis suppression was evaluated in four trials (Trial A, B, C and D) following the application of calcipotriene and betamethasone dipropionate ointment.

In Trial A, calcipotriene and betamethasone dipropionate ointment was applied once daily for 4 weeks to adult subjects (N = 12) with plaque psoriasis to study its effects on the hypothalamic-pituitary-adrenal (HPA) axis. Of eleven subjects tested, none demonstrated adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤ 18 mcg/dL.

In Trial B, calcipotriene and betamethasone dipropionate ointment was evaluated in adult subjects with plaque psoriasis (N = 19). One subject demonstrated adrenal suppression.

In Trial C, HPA axis suppression was evaluated in adult subjects (N=32) with extensive plaque psoriasis involving at least 30% of the scalp and, in total, 15-30% of the body surface area. Treatment consisted of once daily application of calcipotriene and betamethasone dipropionate topical suspension on the scalp in combination with calcipotriene and betamethasone dipropionate ointment on the body. Adrenal suppression as indicated by a 30-minutes post-stimulation cortisol level < 18 mcg/dL was observed in 5 of 32 subjects (15.6%) after 4 weeks of treatment as per the recommended duration of use [see Dosage and Administration (2)].

In Trial D, HPA axis suppression was evaluated in subjects 12 to 17 years (N=32) with plaque psoriasis of the body involving 5-30% of the body surface area. Treatment consisted of once daily application of calcipotriene and betamethasone dipropionate ointment to the affected areas for up to 4 weeks. Mean weekly dose was 29.6 g with a range of 8.1-55.8 g/week. Adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤18 mcg/dL was observed in none of 32 evaluable subjects after 4 weeks of treatment [see Use in Specific Populations (8.4)].

Effects on Calcium Metabolism

In Trial C described above, the effects of once daily application of calcipotriene and betamethasone dipropionate ointment on the body in combination with calcipotriene and betamethasone dipropionate topical suspension on the scalp on calcium metabolism were also examined. Elevated urinary calcium levels outside the normal range were observed in 1 of 35 subjects (2.9%) after 4 weeks of treatment.

In Trial D described above, calcium metabolism was evaluated in a total of 33 subjects aged 12 to 17 years with plaque psoriasis involving 5-30% of the body surface area who underwent once daily application of calcipotriene and betamethasone dipropionate ointment for up to 4 weeks. No cases of hypercalcemia and no clinically relevant changes in urinary calcium were reported. However, one subject had a normal urinary calcium: creatinine ratio at baseline (3.75 mmol/g), which increased above the normal range at week 4 (16 mmol/g). There were no relevant changes in albumin-corrected serum calcium or other markers of calcium metabolism for this subject. The clinical significance of this finding is unknown.