Abstracts

Rationale: Brivaracetam (BRV) was approved for use in the United States and Europe in 2016 as a selective, high-affinity synaptic vesicle 2A (SV2A) ligand, with an elimination half-life of approximately 9h and significantly faster onset of action when compared with levetiracetam. This novel medication has potentially less adverse psychiatric side effects and improved tolerability when compared to levetiracetam. There are few reports of BRV use in pregnancy: one study of two pregnancies reported that BRV serum concentrations remained stable; another of three pregnancies reported no malformations and only one with breakthrough focal seizures. Additional data on pregnancy-related BRV pharmacokinetic changes are needed to inform strategies for therapeutic drug monitoring (TDM).

Methods: A prospective REDCap database of antiseizure medication doses, serum concentrations, and gestational/postpartum age is maintained in the Epilepsy-OB program at Brigham and Women’s Hospital. The database was searched for women on BRV, and additional information was obtained by medical record review for the patients of interest. Clearance was calculated as BRV serum Concentration (ng/mL) /daily Dose (mg/kg/day) (C/D) ratios.

Results: Two women met inclusion criteria. Patient A was a 39yo woman with a history of focal epilepsy since 30yo. She initially failed pregabalin and lamotrigine. Her most recent preconception regimen included levetiracetam and oxcarbazepine, with intolerability due to worsening mood and hyponatremia, respectively. On this regimen, her preconception seizure frequency was daily for focal and monthly for focal-to-bilateral tonic-clonic seizures. She was switched to BRV and eslicarbazepine just before an unplanned pregnancy. During pregnancy, she had 2-3 focal seizures with impaired awareness per week and a total of 3-4 FBTC seizures (one during the first trimester and 2-3 during the third). The BRV C/D ratio reached a nadir at 36 weeks, 32.7% below its peak. She delivered a healthy baby with APGAR scores >7 and no neonatal complications.

Patient B was a 32yo woman with a history of juvenile myoclonic epilepsy since 16yo. She had good seizure control with valproate monotherapy for years. She presented with an unplanned pregnancy at 5weeks GA and was transitioned from valproate to levetiracetam, but experienced severe mood adverse effects. She was then transitioned from levetiracetam to BRV at 12weeks GA. She remained seizure-free with good BRV tolerance until her 3^rd trimester, when she had breakthrough absence seizures and one GTC Seizure. Low-dose valproate was added at 30weeks GA. Notably, the ratio of BRV C/D ratio declined precipitously during the 3^rd trimester by 61.9% from values at 20 weeks GA. The patient delivered a healthy baby with no neonatal complications.

Conclusions: We present a case series of two pregnant women on BRV. Further investigation is necessary to assess BRV use in larger cohorts, with baseline measurements, formal pharmacokinetic modeling with hours post-dose, and assessment of seizure control relative to alterations in concentrations. Based on our observed clearance fluctuations, TDM is recommended for patients on BRV.

Funding: Please list any funding that was received in support of this abstract.: N/A.