• L Bensouda-Grimaldi, A-P Jonville-Béra, E Mouret, E Elefant, H Dhellot, C Delmas, T Gouin, P Coste, E Autret-Leca, and les Centres Régionaux de Pharmacovigilance.
• Service de Pharmacologie, Centre Régional de Pharmacovigilance et d'Information sur le médicament, Université François Rabelais, Hôpital Bretonneau, Tours.
• Ann Dermatol Vener. 2005 May 1;132(5):415-23.

IntroductionThe aim of this survey is to ascertain if the incidence of isotretinoin exposed pregnancies was reduced by the late recommendations of prescription and issue (AMM modification on 06/08/2001 and 25/09/2001).MethodsAll isotretinoin exposed pregnancies registered by the French Regional Drug Monitoring Centres, the Information Centre for Teratogenic Agents and Roche (Roaccutane), Pierre Fabre (Curacné Gé) and Expanscience (Procuta Gé) laboratories, from January 1st, 1999 to December 31st, 2002, were analysed. Enforcement of the strengthening of isotretinoin prescription recommendations was analysed on a sample of 68 prescriptions from 45 pharmacies throughout France.ResultsIn 4 years, 103 isotretinoin exposed pregnancies (Roaccutane 97 p. 100, Curacné(R) Gé 3 p. 100) during teratogenic risk period, were registered. Pregnancy started less than one month after isotretinoin stopping (37 p. 100), during the treatment (43 p. 100), or was in progress when the treatment was initiated (20 p. 100). The reason of the 22 lacking contraception was known 12 times, i.e. an absence of prescription (6 times), a refusal to take a prescribed contraception (3 times) and a self-medication (3 times). Among the 71 pregnancies whose contraceptive status is known, 48 p. 100 could had been avoided if recommendations had been followed (pregnancies due to a premature stopping or an absence of contraception). The issue of pregnancies is a voluntary termination in 60 cases (87 p. 100). Malformations frequency is 25 p. 100. Incidence of isotretinoin exposed pregnancies remained stable, 0.26/1000 treated women (vs 0.34 after 2001's AMM modifications). Of 68 prescriptions studied, 23 (24 p. 100) carried all the legal warnings, which is close to the previous survey's results. Contraception was in accordance with the recommendations in 78 p. 100 of cases and women learned and applied information given in 38 p. 100 of cases. At last, only 6 patients (9 p. 100) have both a correctly written prescription, a contraception and a time between the pregnancy test date and prescription and issue dates, in accordance with the licence and have had a correct information and understood it. Regarding the previous survey, pregnancy test before treatment was more often prescribed (96 p. 100 vs 88 p. 100). On the other hand, less women knew the necessity to keep on taking contraception one month after isotretinoin stopping (82 p. 100 vs 93 p. 100).ConclusionDespite 3 successive isotretinoin prescription and issue recommendations strengthening in childbearing women, pregnancies can't be totally avoided. Bad compliance concerns the prescription and/or an incomplete or not understood information by the patient who does not scrupulously apply the care and contraception agreement. However, this study does not allow to assess the proportion of issued prescriptions despite their non-accordance with the licence criteria. The National Commission of Pharmacovigilance did not like to limit isotretinoin prescription to dermatologists only. It estimates that the administrative authority must intensify information by dermatologists, general practitioners and pharmacists, about measures to take to avoid an exposure to isotretinoin during pregnancy.

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