Abstracts

Rationale: Despite increasing use in pregnancy little is known concerning levetiracetam pharmacokinetics during pregnancy, particularly when used as single drug therapy. Understanding and predicting changes in serum blood levels would be important for maintaining seizure control during pregnancy. Methods: We reviewed sixteen pregnancies in thirteen women taking levetiracetam monotherapy for seizures. Serum levels were determined monthly and doses were adjusted to maintain individualized clinically therapeutic pre-pregnancy baselines. The timing of the blood draws relative to the last dose was standardized. Dose was adjusted regardless in any patient with breakthrough seizures. Levetiracetam serum levels, seizure rates, and pregnancy outcomes were reviewed. Results: Baseline levetiracetam doses ranged from 750 mg to 2,500 mg per day. All baseline levetiracetam levels were considered clinically therapeutic based on historical seizure control and anticonvulsant levels. Thirteen out of sixteen patients required dose escalation during pregnancy, with percent change ranging from 20-166.7% from baseline. No patient required dose reduction. The need for dose change was uniformly distributed across all trimesters. Doses increased further for all thirteen patients as the pregnancy progressed. Only three patients had no dose adjustment during pregnancy. For the three repeat pregnancies, levetiracetam dose changes for the first pregnancy were not predictive of changes in subsequent pregnancies. Seizure frequency rates ranged from 2 to 13 seizures for the four patients with seizures prior to conception over a 9 month pre-pregnancy baseline period. Fifteen patients remained seizure free during the entirety of the pregnancy. One patient only had a habitual seizure out of all sixteen pregnancies. Dose adjustment based on seizure frequency thus was needed for this patient, despite having maintained the target pre-pregnancy serum levels before this seizure. There were no major congenital fetal malformations or miscarriages. There was one maternal medical complication of pre-eclampsia. Conclusions: Levetiracetam levels can be expected to decline during pregnancy when used as single drug therapy. This can occur in any trimester and is seen in most if not every case. In addition, there is marked variance between repeat pregnancies in a given individual despite standardized serum blood testing and fixed formulation. Standardized monthly blood levels and timely dose adjustments appeared to be a successful management strategy. Funding: none