Abstracts

Rationale: Pharmacologic management of epilepsy in women with epilepsy (WWE) presents unique challenges during pregnancy. Significant physiological changes during pregnancy may affect pharmacokinetics of AEDs given to pregnant patients, resulting in fluctuations in serum drug concentrations. There is a paucity of data on the pharmacokinetic changes and safety of zonisamide during pregnancy. We report our observations with zonisamide treatment in one singleton and one twin pregnancy.Methods: A retrospective review was done on patients who were referred to the Pregnancy/Contraception Counseling and Prenatal Epilepsy Clinic (PPEC) at the University of Colorado Hospital between July 2014 to June 2015. Patients who were on zonisamide throughout their pregnancy with at least one blood level for each trimester were identified. Serum blood levels were used to calculate apparent drug clearance at multiple points during pregnancy. Drug doses and changes in seizure activity were abstracted. Significant clinical events and the outcome of the pregnancy were also reviewed.Results: Two patients who were on monotherapy zonisamide throughout their pregnancies were identified. Both patients had Juvenile Myoclonic Epilepsy (JME). One of the patients had a singleton pregnancy and the other had dichorionic diamniotic twins. Significant changes in apparent drug clearance were observed in both patients. In the singleton pregnancy, peak clearance increased by 228% relative to the non-pregnant baseline in the third trimester. She remained seizure-free and there were no significant clinical events throughout her pregnancy. In the twin pregnancy, peak clearance increased by 223% from non-pregnant baseline in the second trimester and appeared to decrease in the third trimester. She had episodes of myoclonic seizures and severe nausea and vomiting in the first trimester. Both patients had uneventful deliveries with no fetal complications or malformations reportedConclusions: Zonisamide clearance increases significantly from the second trimester. Close monitoring of serum drug levels throughout the pregnancy and preemptive dose adjustments may be useful to reduce the risk of seizure recurrence during pregnancy. More data on the pharmacokinetic changes and safety of zonisamide in pregnancy is needed