Daivonex Mechanism of Action

Pharmacology: Daivonex ointment is a topical formulation of the vitamin D derivative, calcipotriol, which induces differentiation and suppresses proliferation of skin cells (keratinocytes). Daivonex ointment thus normalises abnormal cell proliferation and differentiation in psoriatic skin.
Toxicology: Preclinical safety data: The effect on the calcium metabolism is approximately 100 times less than that of the hormonally active form of vitamin D₃. A dermal carcinogenicity study in mice showed no indications of increased carcinogenic risks.
Calcipotriol solution was applied topically for up to 24 months at doses of 3, 10 and 30 μg/kg/day (corresponding to 9, 30 and 90 μg/m²/day). The high-dose was considered to be the Maximum Tolerated Dose for dermal treatment of mice with calcipotriol. Survival was decreased at 10 and 30 μg/kg/day, particularly in the males. The reduced survival was associated with an increased incidence of obstructive uropathy, most probably caused by treatment-related changes in the urinary composition. This is an expected effect of treatment with high doses of calcipotriol or other vitamin D analogues. There were no dermal effects and no dermal or systemic carcinogenicity.
Calcipotriol has shown maternal and fetal toxicity in rats and rabbits when given by the oral route at doses of 54 μg/kg/day and 12 μg/kg/day, respectively. The fetal abnormalities observed with concomitant maternal toxicity included signs indicative of skeletal immaturity (incomplete ossification of the pubic bones and forelimb phalanges and enlarged fontanelles) and an increased incidence of supernumerary ribs.
In a study where albino hairless mice were repeatedly exposed to both ultraviolet (UV) radiation and topically applied calcipotriol for 40 weeks at the same dose levels as in the dermal carcinogenicity study, a reduction in the time required for UV radiation to induce the formation of skin tumours was observed (statistically significant in males only), suggesting that calcipotriol may enhance the effect of UV radiation to induce skin tumours. The clinical relevance of this finding is unknown.