Contraindications
Calcipotriol/betamethasone dipropionate is contraindicated in patients with hypersensitivity to either glucocorticoids or vitamin D or disorders in calcium metabolism. This drug is also contraindicated for patients with erythrodermic, exfoliative, or pustular psoriasis. Adverse effects
A number of clinical studies have been conducted to investigate possible adverse events of this fixed combination corticosteroid and vitamin D analog. Safety and tolerability of calcipotriol/betamethasone dipropionate (Cal/BD) ointment has been assessed in a combined total of 2448 patients, exposed to treatment for 4 or 8 weeks (median weekly dose of 24.5 g). The most common adverse events for patients receiving Cal/BD were pruritus (3.1%), headache (2.8%), and nasopharyngitis (2.3%). Lesional/perilesional adverse events, defined as an adverse event located ≤2 cm from the lesional border, were reported by 8.7% of patients treated with Cal/BD ointment. Median time to onset of lesional/perilesional adverse events was 7 days.Adverse events during treatment with the foam formulation have been evaluated in three 4-week randomized, multicenter, prospective vehicle- and/or active-controlled clinical trials of subjects with plaque psoriasis. The median weekly dose was 24.8 g. Application site irritation, application site pruritus (itching), folliculitis (inflammation of hair follicles), skin hypopigmentation (loss of skin color), hypercalcemia (increased blood calcium levels), urticaria, and exacerbation of psoriasis were reported in <1% of subjects. Local long-term adverse effects of continuous steroid exposure may include skin atrophy, stretch marks, telangiectasia (spider veins), dryness, local infections, and miliaria ("prickly heat").
Effects on calcium metabolism
In patients treated with both calcipotriol/betamethasone dipropionate (Cal/BD) ointment on the body and Cal/BD topical suspension on the scalp (n=35), 1 patient (2.9%) had elevated urinary calcium levels after 4 weeks of treatment.Three studies of Cal/BD topical suspension have evaluated treatment effects on calcium metabolism. In 2 of the 3 trials (n=32 and n=43), elevated urinary calcium levels outside the normal range were observed in 2 patients each. In the third trial (n=109), no clinically relevant changes in urinary calcium were reported.Potential effects on calcium metabolism have been evaluated in three randomized, multicenter, prospective, vehicle- and/or active-controlled trials of the foam formulation enrolling 564 adults with plaque psoriasis. The foam was applied once daily for four weeks. In these trials, three subjects had serum calcium levels elevated above the upper limit of normal. Urinary calcium elevations above normal were reported in 17 subjects.In a published multicenter, open-label, single-arm trial of the foam formulation, 35 adults with plaque psoriasis applied the foam once daily to all lesions on the trunk, limbs, and scalp for four weeks. No elevations of serum calcium, urinary calcium, or the ratio of urinary calcium to creatinine above the upper limit of normal were observed. History
The combination was developed by LEO Pharma. To combine them, new non-aqueous non-alcohol formulations had to be found to avoid mutual degradation of the two active substances while also achieving the desired skin absorption.