Antifungal (Topical)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of butenafine in human pregnancy have been located. The animal data suggest low risk, as does the very low systemic concentrations. Although a more complete assessment of the embryo–fetal risk cannot be made, the topical use of this agent appears to low risk in human pregnancy.
FETAL RISK SUMMARY
Butenafine, a synthetic antifungal, is a benzylamine derivative with a mechanism of action similar to the allylamine class of antifungal agents. The agent is available as a cream to be applied to the skin. Butenafine is indicated for the topical treatment of the dermatologic infection, tinea (pityriasis) versicolor due to Malassezia furfur (formerly Pityrosporum orbiculare). Small amounts of butenafine are absorbed into the systemic circulation. After the application 6 and 20 g/day for 14 days, the mean peak plasma concentrations were 1.4 and 5.0 ng/mL, respectively. The biphasic plasma elimination half-lives were estimated to be 35 and >150 hours, respectively. The antifungal agent is metabolized (1).
Reproduction studies have been conducted in rats and rabbits. In rats during organogenesis, daily SC doses up to 0.5 times the maximum recommended human dose for tinea versicolor based on BSA (MRHD) were not teratogenic. In a peri- and postnatal study with rats, daily oral doses up to 2.5 times the MRHD caused no treatment-related effects on postnatal survival, development of the F1 generation, or their subsequent maturation and fertility. In rabbits during organogenesis, daily oral doses up to 16 times the MRHD revealed no evidence of treatment-related fetal harm (1).
Studies for carcinogenic effects have not been conducted with butenafine, but assays for mutagenic and clastogenic effects were negative. No adverse effects on male and female rat fertility were observed with daily SC doses up to 0.5 times the MRHD (1).
It is not known if butenafine crosses the placenta. The molecular weight (about 318 for the free base) and long plasma elimination half-life suggest that the drug will cross to the embryo and fetus, but the very small amounts in the systemic circulation suggest that the exposure will be clinically insignificant.
BREASTFEEDING SUMMARY
No reports describing the use of butenafine during human lactation have been located. The molecular weight (about 318 for the free base) and long plasma elimination half-life suggest that the drug will be excreted into breast milk, but the very small amounts in the systemic circulation suggest that the effects on a nursing infant from this exposure will be clinically insignificant.
Reference
1.Product information. Mentax. Mylan Pharmaceuticals, 2007.