Abstracts

Rationale: Congenital effect of antiepileptic drugs (AEDs) on the unborn fetus remains a topic of vital importance. A better understanding of this topic may result by evaluating multiple sources of information from a variety of global sources: medical literature, spontaneously reported postmarketing events, and events reported to the company by pregnancy registries. We report on the pregnancy and fetal/neonatal outcomes following maternal exposure to topiramate (TPM), based on postmarketing safety surveillance data from the Johnson & Johnson Pharmaceutical Research & Development (J&JPRD) worldwide database. Methods: A search of the J&JPRD Global Medical Safety worldwide pharmacovigilance database, using a selection of preferred terms from the Medical Dictionary of Regulatory Activities, was performed to identify all cases of pregnancy and fetal/neonatal outcomes reported in association with either TPM monotherapy or polytherapy from its first market launch (international birth date, 18 July 1995) to 31 March 2011. The main measures were the patterns and reporting rates of pregnancy (stillbirth and spontaneous and induced abortion) and fetal/neonatal outcomes (major congenital abnormalities) for women administered TPM monotherapy during pregnancy. The data were summarized using descriptive statistics.Results: Overall, 1,355 pregnancies were reported in women who were receiving TPM. The majority of the known adverse pregnancy and fetal/neonatal outcomes were reported from the US (41%). Maternal age was reported in 893 cases, the mean age was 28.6 years and the range was 16-48 years. The majority of TPM use was for the treatment of epilepsy (764 [56%]). Additionally, TPM was also used for migraine (202 [15%]), other conditions (148 [11%]), and unknown indications (241 [18%]). Data on use of either TPM mono- or polytherapy for any indication was available for 789 (58%) of the 1,355 patients; 412 (30%) were categorized as using TPM monotherapy, and 377 (28%) as using polytherapy. Information regarding outcome was available for 637 (47%) reported pregnancies: 490 (77%) were live-born infants, 87 (14%) were spontaneous abortions, 43 (7%) were elective abortions, and 17 (3%) were fetal deaths. Of these 637 known pregnancy outcomes, 210 (33%) were TPM monotherapy and 248 (39%) were polytherapy. Treatment for the remaining 179 (28%) of these cases was not reported. In TPM monotherapy cases, there were 13 major malformations and 35 spontaneous abortions. The most frequently reported major malformations were cleft lip/palate (n=5) and hypospadias (n= 4). Conclusions: This comprehensive review of the J&JPRD Global Medical Safety database provides additional information on TPM exposure during pregnancy. Underreporting of the total pregnancy population exposed to drug, reporting bias of adverse outcomes, and retrospective analysis of data should be taken into consideration. The pattern of major malformations reported here is consistent with previous reports. TPM should be used in pregnancy only if the potential benefit outweighs the potential risk. Funding: J&JPRD