Effects of low-dose titration on the tolerability and safety of perampanel

• Published in: Epilepsy & behavior 2023-06, Vol.143, p.109213, Article 109213
• Main Authors: Yamamoto, Yoshiaki, Shiratani, Yuka, Nishida, Takuji, Usui, Naotaka, Imai, Katsumi, Kagawa, Yoshiyuki, Takahashi, Yukitoshi
• Format: Article
• Language: English
• Subjects: Adverse events; Anticonvulsants - adverse effects; Humans; Nitriles; Perampanel; Pyridones - adverse effects; Retrospective Studies; Therapeutic drug monitoring; Titration; Treatment Outcome
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2023.109213

•Relation between perampanel titration and safety and tolerability was investigated.•Early occurrence of adverse events led to increased risk of perampanel withdrawal.•Low-dose titration significantly decreased the incidence risk of adverse events.•Patients without inducers showed large variability in serum concentrations.•When a patient is not taking inducers, low-dose titration is recommended. To evaluate the effects of low-dose titration on the tolerability and safety of perampanel. We retrospectively reviewed the records of 1065 patients who started perampanel therapy and compared the incidence of adverse events after standard titration (Group A: starting dose, 2 mg/day; titration speed, 2 mg/2 weeks or longer) and low-dose titration (Group B: starting dose, < 1 mg/day; titration speed, < 1 mg/2 weeks or longer). Adverse events were reported in 158 patients (14.8%) within the initial first 90 days of starting perampanel (mean concentration, 331 ng/mL). At 90 days, the cumulative incidence of adverse events was significantly higher in Group A than in Group B (24.5% vs. 16.3%, respectively; log-rank test p