Teratogenicity

Retinoids are known to be teratogenic and can lead to fetal abnormalities. The birth defects characteristically induced by retinoids, so-called retinoic acid embryopathy, include central nervous system abnormalities (hydrocephalus and microcephaly), external ear abnormalities (anotia and small or absent external auditory canals), cardiovascular abnormalities (septal wall and aortic defects), facial dysmorphia, eye abnormalities (microphthalmia), thymus gland and bone abnormalities. In addition, premature births, parathyroid hormone deficiency, and cases of low IQ in the absence of other central system abnormalities have been reported. Retinoid effects on neural crest cells during the fourth week after fertilization may be responsible for many of the observed malformations. Serum levels of the p subunit of human chorionic gonadotropin should be checked before therapy, and effective contraception is mandatory during and after treatment. Isotretinoin has a short half-life, and, therefore, contraceptive measures need to be taken for only 1 month after cessation of treatment. Etretinate and acitretin both have a long half-life. Although acitretin has a

much shorter half-life than etretinate, it is recommended that pregnancy should not occur for at least 3 years after the cessation of acitretin therapy, since some patients back-metabolize acitretin to etretinate (Fig. 27.5). Males can safely father children even when they are taking the drug (Brecher and Orlow 2003, Duna and Cash1995,Lo et al. 1989).

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