Effects of Perampanel Slow Dose Titration on Tolerability in Japanese Epilepsy Patients
Abstract number :
2.258
Submission category :
7. Anti-seizure Medications / 7D. Drug Side Effects
Year :
2022
Submission ID :
2204963
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:27 AM
Authors :
Yoshiaki Yamamoto, PhD – National Epilepsy Center, Shizuoka, Japan; Naotaka Usui, MD – National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders; Katsumi Imai, MD – National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders; Yoshiyuki Kagawa, PhD – University of Shizuoka; Yukitoshi Takahashi, MD – National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders
Rationale: Perampanel is a new antiseizure medication that acts as a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor antagonist. This drug has a long half-life (53-136 hours), a high oral bioavailability (approximately 100%), and it is mainly metabolized by cytochrome P450 3A4. The aim of this study was to compare the tolerability and safety of two different titrations of perampanel (slow and standard) in Japanese patients with epilepsy.
Methods: We retrospectively reviewed the clinical records of 895 patients aged from 1 to 86 years who commenced perampanel therapy at our hospital and assessed the time to treatment failure within 180 days after starting perampanel therapy. In slow titration group, perampanel was initiated at a daily dose of less than 1 mg/day for at least 2 weeks. The other patients received 2 mg of perampanel (standard titration group). In both groups, the maximum dose was 12 mg/day. The study protocol was approved by the ethics committee of the National Epilepsy Center (Shizuoka, Japan).
Results: The total withdrawal rate in the slow titration group and the standard titration group was 15.8 and 19.3%, respectively. However, there was no difference in the time to treatment failure between both groups (162.8 vs. 159.8 days, log rank test, p=0.19). During study period, adverse events were reported by 159 patients (17.8%), and all of them required discontinuation or dose reduction of perampanel. The incidence rate of adverse events was higher in patients receiving standard titration therapy than in patients receiving slow titration therapy (20.8% vs 14.4%). Multiple logistic regression analysis also showed that the perampanel slow dose titration decreased the incidence risk of adverse events (adjusted odds ratio, 0.67; 95% confidence interval, 0.47-0.95, p=0.026).
Conclusions: Our study suggested that it is important to carefully set the starting dose for treatment with perampanel. Perampanel slow dose titration can contribute to decreasing the risk of early adverse events.
Funding: Not applicable
Anti-seizure Medications