Efficacy, tolerability and pharmacokinetic variability of brivaracetam in adults with difficult-to-treat epilepsy

Abstract

Purpose: Brivaracetam (BRV) is one of our latest antiseizure medications (ASMs). It is an analogue of levetiracetam with limited real-life experience. The purpose of this study was to evaluate clinical experience with BRV with focus on efficacy, tolerability and pharmacokinetic variability among adult patients with difficult-to-treat epilepsy. Methods: We retrospectively collected clinical and laboratory data from patients aged > 18 years who initiated treatment with BRV during 2016-2019 and were followed for > one year or cessation of BRV. Results: The study cohort consisted of 120 adults with drug-resistant epilepsy. Serum concentrations of BRV were available in 72 patients. After one-year follow-up, the retention rate of BRV was 52%. Fifty-seven patients (48%) were responders (>50 reduction of seizure frequency), of whom six became seizure free. Adverse effects were reported in 78 patients (65%); 37 (31%) experienced psychiatric problems like increased irritability, anxiety and depressive symptoms. The mean daily BRV dose was 159 mg (SD 80 mg) and the mean serum concentration 5.4 μmol/L (SD 4.1 μmol/L). In 24 patients, BRV replaced levetiracetam. Pharmacokinetic variability between patients was considerable; 14-fold variation in concentration/dose (C/D)-ratios. Concomitant use of enzyme-inducing ASMs decreased the C/D-ratio by 48%. There were no significant differences in serum concentrations between responders vs. non-responders, or those who experienced adverse effects or not. Conclusion: After > 1 year of treatment with BRV, we found a responder rate of 48% in adult patients with difficult-to-treat epilepsy. The drug was largely well tolerated, but one third experienced psychiatric adverse effects. The combination of clinical and pharmacokinetic data provides insight into factors contributing to efficacy and tolerability of new ASMs. Keywords: Antiseizure medications; Efficacy; Epilepsy; Therapeutic drug monitoring; Tolerability. Copyright © 2022 Elsevier B.V. All rights reserved.