Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures

Biton, V., Gil-Nagel, A., Brodie, M.J., DeRossett, S.E. and Nohria, V. (2013) Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures. Epilepsy Research, 107(1-2), pp. 138-145. (doi: 10.1016/j.eplepsyres.2013.08.021)

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Abstract

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated potassium-channel KCNQ2–5 (Kv 7.2–7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N = 73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300 mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150 mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200 mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p = 0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p = 0.010) but not in the medium-titration group (p = 0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brodie, Professor Martin
Authors: Biton, V., Gil-Nagel, A., Brodie, M.J., DeRossett, S.E., and Nohria, V.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Epilepsy Research
ISSN:0920-1211
ISSN (Online):1872-6844

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