Dermatologic Agent (Anti-Psoriatic)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of calcipotriene in human pregnancy have been located. The animal data suggest moderate risk, but there is no evidence that vitamin D derivatives cause human developmental toxicity. Only low amounts of the drug are absorbed into the systemic circulation and the embryo–fetal risk is probably similar to calcitriol, a vitamin considered compatible with pregnancy (see Calcitriol). Two reviews discussing the treatment of psoriasis, one in 2002 (1) and the other in 2005 (2), considered the topical use of calcipotriene to be safe in pregnancy. Mild hypercalcemia has been observed in a newborn exposed in utero to calcitriol and is a potential complication with calcipotriene.
FETAL RISK SUMMARY
Calcipotriene, a synthetic derivative of vitamin D3 (calcitriol), is available in cream, ointment, and solution preparations. It is indicated for the treatment of plaque psoriasis in adults. Clinical studies with the ointment found that about 6% and 5% of the applied dose is absorbed systemically when applied to psoriasis plaques and normal skin, respectively. Much of the absorbed drug is converted to inactive metabolites within 24 hours of application. Metabolism is thought to be similar to calcitriol (3,4). Systemic absorption of the cream or solution has not been studied (3).
Reproduction studies have been conducted in rats and rabbits with oral calcipotriene where the expected bioavailability of the dose was about 40%–60%. The maternal and fetal calculated no-effect exposures in the rat and rabbit studies were about equal to the expected human systemic exposure level from dermal application based on BSA (HSEL). In rats, oral doses about 7.4 times the HSEL resulted in a significantly higher incidence of skeletal abnormalities consisting primarily of enlarged fontanelles (thought to be due to the drug’s effect on calcium metabolism) and extra ribs. In rabbits, increased maternal and fetal toxicity was noted at about 7.5 times the HSEL. Doses that were about 17.5 times the HSEL resulted in fetuses with a significant increase in the incidences of pubic bones, forelimb phalanges, and incomplete bone ossification (3,4).
Long-term carcinogenesis studies in mice with topical calcipotriene, without exposure to ultraviolet radiation (UVR), caused no significant changes in tumor incidence. However, when mice also were exposed to UVR, the results suggested that the drug enhanced the effect of UVR to induce skin tumors. Calcipotriene was not mutagenic in multiple assays and, at oral doses up to about 7.5 times the HSEL, did not impair the fertility or reproductive performance in rats (3,4).
It is not known if calcipotriene crosses the human placenta. However, the systemic disposition of calcipotriene is expected to be similar to that of the naturally occurring calcitriol that does enter the fetal circulation (4).
BREASTFEEDING SUMMARY
No reports describing the use of calcipotriene during human lactation have been located. Only small amounts are absorbed into the systemic circulation and probably are excreted into breast milk. However, calcipotriene is a synthetic derivative of calcitriol, an active form of vitamin D. Vitamin D is compatible with breastfeeding (see Vitamin D), and the topical use of calcipotriene probably can be classified similarly.
References
1.Tauscher AE, Fleischer AB Jr, Phelps KC, Feldman SR. Psoriasis and pregnancy. J Cutan Med Surg 2002;6:561–70.
2.Lebwohl M. A clinician’s paradigm in the treatment of psoriasis. J Am Acad Dermatol 2005;53:S59–69.
3.Product information. Dovonex cream. LEO Pharma, 2010.
4.Product information. Dovonex ointment. Bristol-Myers Squibb, 2010.