Abstracts

Rationale: Epilepsy treatment during pregnancy is necessary for uncontrolled seizures but must be balanced with the known risk of fetal exposure to anti-epileptic drugs (AEDs). Since a significant number of prenatal exposures is required to draw meaningful conclusions on potential AED-related pre-and post-natal adverse effects, pregnancy registries have been established, including the UCB AED Pregnancy Registry, which monitors pregnancy exposures and outcomes in pregnant women and their offspring exposed to any UCB AEDs. Lacosamide (LCM, Vimpat®) is a new AED marketed by UCB that was recently approved as an adjunctive treatment in partial-onset seizures in patients with epilepsy aged 17 years and older. LCM did not appear to provide a higher than expected risk of teratogenicity in animal models. Given its recent approval and corresponding lack of pregnancy exposure data, initial observations of exposure to LCM during pregnancy in the LCM clinical development program are summarized here. Methods: Subjects with confirmed pregnancies in all LCM clinical trials investigating the effects of oral and iv LCM (100-600mg/d) were monitored, and pregnancy outcome was recorded. Per protocol, subjects becoming pregnant during the trials had to be withdrawn. Results: A total of 10 pregnancies were confirmed in 10 subjects during the clinical development program for LCM (dose range 200 to 800 mg/day), with 2 pregnancies in healthy subjects (Phase I trials), 7 in subjects with partial-onset seizures and 1 in a subject with diabetic neuropathic pain. Two of the pregnancies were electively terminated, 2 resulted in a spontaneous abortion, and one was classified as a missed abortion resulting from a misplaced IUD. Five pregnancies were completed and resulted in delivery of healthy offspring with no evidence of congenital abnormalities. Women with confirmed pregnancy tests were withdrawn from the trials, and, therefore the overall exposure to LCM during pregnancy was limited to the first trimester. Conclusions: There is only limited experience with outcome of prenatal exposure to LCM. The five children born after completed pregnancy with first trimester exposure to LCM were born without major congenital malformations. However, the overall risk of prenatal exposure to LCM for the unborn child remains unknown. As indicated in the US Product Insert, LCM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Doctors are encouraged to register pregnant patients through the UCB AED Pregnancy Registry (toll free number 1-888-537-7734). Reports will continue to be collected formally to provide a more comprehensive evaluation of pregnancy outcome and long-term follow-up of live-born infants.