Isotretinoin exposure during pregnancy: assessment of spontaneous reports in France.

ABSTRACT

BACKGROUND: In three previous studies, we have shown that pregnant women were still being exposed to isotretinoin and that compliance with recommendations was incomplete. The relaxation of these recommendations (summary of product characteristics 2004), combined with the release of generic brands, encouraged us to carry out a fourth study. OBJECTIVE: To assess isotretinoin exposure during pregnancy following the application of less stringent recommendations and the marketing of generic isotretinoin brands. METHODS: All cases of isotretinoin exposure during pregnancy, between 1 January 2003 and 31 December 2006, spontaneously reported to pharmacovigilance centres, the Teratogenic Agent Information Centre, and pharmaceutical companies in France were assessed. Cases were classified for analysis into the following groups 'conception <1 month after isotretinoin discontinuation', 'conception during isotretinoin treatment' and 'patient already pregnant when isotretinoin was started'. The rate of spontaneously reported isotretinoin exposure during pregnancy was estimated by dividing the number of isotretinoin-exposed pregnancies by the number of women of childbearing age treated with isotretinoin. RESULTS: Over 4 years, 147 cases of isotretinoin exposure during the teratogenic risk period were spontaneously reported, i.e. 'conception <1 month after isotretinoin discontinuation' (23%), 'conception during isotretinoin treatment' (61%), and 'patient already pregnant when isotretinoin was started' (16%). Nineteen percent of the patients did not use any form of contraception. In 23% of the patients, the method of contraception used did not comply with recommendations, while in 86% of the cases, isotretinoin was prescribed by a dermatologist. Among the 44 pregnancies with available data on fetuses or neonates, there were two (4.5%) malformations compatible with the time of exposure and with isotretinoin embryopathy. The rate of spontaneously reported isotretinoin exposure during pregnancy has increased by approximately 30%, from 0.32 (95% CI 0.26, 0.38) to 0.41 (95% CI 0.34, 0.49) per 1000 women of childbearing age treated since 1999-2002. CONCLUSIONS: We suggest that recommendations be tightened, with specific information regarding the most effective contraceptive method combined with compulsory monthly pregnancy testing during treatment. The French Drug Agency has informed the European Medicines Agency of the need for measures aimed at improving compliance.