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Mechanism of Action

Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension combines the pharmacological effects of calcipotriene hydrate as a synthetic vitamin D3 analogue and betamethasone dipropionate as a synthetic corticosteroid. However, while their pharmacologic and clinical effects are known, the exact mechanisms of their actions in psoriasis vulgaris are unknown.

Pharmacodynamics

Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression:

HPA axis suppression was evaluated in adult subjects (N=32) with extensive 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 Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension on the scalp in combination with Taclonex® Ointment on the body for 4 to 8 weeks. Adrenal suppression as indicated by a 30-minute post-stimulation cortisol level ≤ 18 mcg/dL was observed in 5 of 32 subjects (15.6%) after 4 weeks of treatment and in 2 of 11 subjects (18.2%) who continued treatment for 8 weeks.

Effects on Calcium Metabolism:

In the study described above, the effects of once daily application of Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension on the scalp in combination with Taclonex® Ointment on the body for 4 to 8 weeks on calcium metabolism were also examined. Following once daily application of Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension on the scalp in combination with Taclonex® Ointment on the body, elevated urinary calcium levels outside the normal range were observed in two subjects (one at 4 weeks and one at 8 weeks).

Pharmacokinetics

Absorption

Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension:

The systemic effect of Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension in extensive psoriasis was investigated in the study described above. In this study, the serum levels of calcipotriene and betamethasone dipropionate and their major metabolites were measured after 4 and 8 weeks of once daily application of Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension on the scalp in combination with Taclonex® Ointment on the body. Calcipotriene and betamethasone dipropionate were below the lower limit of quantification in all serum samples of the 34 subjects evaluated.

However, one major metabolite of calcipotriene (MC1080) was quantifiable in 10 of 34 (29.4%) subjects at week 4 and in five of 12 (41.7%) subjects at week 8. The major metabolite of betamethasone dipropionate, betamethasone 17-propionate (B17P) was also quantifiable in 19 of 34 (55.9%) subjects at week 4 and seven of 12 (58.3%) subjects at week 8. The serum concentrations for MC1080 ranged from 20-75 pg/mL. The clinical significance of this finding is unknown.

Metabolism

Calcipotriene:

Calcipotriene metabolism following systemic uptake is rapid and occurs in the liver. The primary metabolites of calcipotriene are less potent than the parent compound.

Calcipotriene is metabolized to MC1046 (the α,ß-unsaturated ketone analog of calcipotriene), which is metabolized further to MC1080 (a saturated ketone analog). MC1080 is the major metabolite in plasma. MC1080 is slowly metabolized to calcitroic acid.

Betamethasone dipropionate:

Betamethasone dipropionate is metabolized to betamethasone 17-propionate and betamethasone, including the 6ß-hydroxy derivatives of those compounds by hydrolysis. Betamethasone 17-propionate (B17P) is the primary metabolite.

Clinical Studies

Controlled Clinical Studies

Two multicenter, randomized, double-blind studies were conducted. In Study One, 1,407 subjects were randomized to one of four treatment groups: Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension, betamethasone dipropionate in the same vehicle, calcipotriene hydrate in the same vehicle, or the vehicle alone. Study Two did not include a vehicle arm; 1,280 subjects were randomized to one of three treatment groups: Taclonex Scalp® (calcipotriene and betamethasone dipropionate topical suspension) Topical Suspension, betamethasone dipropionate in the same vehicle, or calcipotriene hydrate in the same vehicle. Both studies enrolled subjects with moderate to very severe scalp psoriasis. The majority of subjects had disease of moderate severity at baseline. Subjects were treated once daily for 8 weeks.

Efficacy was assessed as the proportion of patients at Week 8 with absent or very mild disease according to an Investigator's Global Assessment of Disease Severity. "Clear" was defined as no evidence of redness, thickness or scaling. "Almost clear" was defined as an overall clinical picture of lesions with the presence of minimal erythema. Table 2 contains the response rates in each of these two trials.

Table 2

Last reviewed on RxList: 6/18/2008
This monograph has been modified to include the generic and brand name in many instances.