Drugs in Pregnancy and Lactation: Tenth Edition

ADAPALENE

Dermatologic Agent

PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk

BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible

PREGNANCY SUMMARY

Adapalene is not teratogenic in two experimental animal species. After chronic use in humans, trace amounts of adapalene have been detected in the systemic circulation. The adverse pregnancy outcome described below is the only report of adapalene exposure in human pregnancy. The combination of animal data and very low systemic bioavailability suggests that any risk to a fetus from inadvertent exposure would be very low, but the nearly complete absence of human data prevents further assessment. Until more experience in pregnancy has been reported, the safest course is to avoid use of this agent in the 1st trimester.

FETAL RISK SUMMARY

Adapalene is used topically (cream, gel, or solution) for the treatment of acne vulgaris. The agent is a retinoid-like compound that is a modulator of cellular differentiation, keratinization, and inflammatory processes. It binds to specific retinoic acid nuclear receptors. Plasma concentrations are very low after chronic topical application (<0.25 ng/mL) (1).

No teratogenic effects were noted in pregnant rats given oral doses up to 120 times the maximum daily human dose (MDHD). Topical application of adapalene to pregnant rats and rabbits up to 150 times the MDHD demonstrated no fetotoxicity and only minimal increases in supernumerary ribs in rats (1).

It is not known if adapalene crosses the human placenta. The molecular weight (about 413) and low plasma concentrations suggest that minimal amounts of drug would be available to cross the placenta.

Only one report describing the use of adapalene during human pregnancy has been located (2). At 22 weeks’ gestation, a small-for-date fetus with anophthalmia was detected by ultrasound examination and the pregnancy was terminated. Anophthalmia and agenesis of the optic chiasma were observed in the aborted fetus. The mother had been treated with adapalene gel (0.3 mg/day) from 1 month before conception until 13 weeks’ gestation. The defects were not thought to be typical of retinoid-induced malformations (heart, central nervous system, thymus, limbs, and craniofacial) (2).

BREASTFEEDING SUMMARY

No reports describing the use of adapalene during lactation have been located. The systemic availability of this drug from topical administration is very low (<25 ng/mL) (1). The amount in breast milk, therefore, should also be very low. It is doubtful that this level, if it is excreted in milk, represents any risk to a nursing infant.

References

1.Product information. Differin. Galderma Laboratories, 2002.

2.Autret E, Berjot M, Jonville-Bera AP, Aubry MC, Moraine C. Anophthalmia and agenesis of optic chiasma associated with adapalene gel in early pregnancy. Lancet 1997;350:339.