Retigabine (ezogabine) as add-on therapy for partial-onset seizures: an update for clinicians

Objective: The present study reviewed the pharmacology, pharmacokinetics, efficacy, and safety of retigabine (ezogabine), a potential agent for use as adjunctive treatment in refractory partial-onset seizures. Methods: A MEDLINE search (1966-May 2011) was conducted using the key words retigabine, ezogabine, D-23129, epilepsy, and anticonvulsant. Bibliographies of all articles retrieved were also reviewed. All studies including humans and published in English with data describing retigabine for the adjunctive treatment of partial-onset seizures were reviewed. Results: Retigabine has been shown to interact with the KCNQ2/KCNQ3 subunits of the potassium channels, GABAA receptors, and weakly block sodium and calcium channels. Retigabine is 50-60% bioavailable, metabolized by N-glucuronidation and N-acetylation, 80% protein bound, and has few drug-drug interactions. Recent data suggest that retigabine may have a role as adjunctive treatment for refractory partial-onset seizures. Placebo-controlled trials demonstrated a 23.4-44.3% reduction in seizure frequency with 50% responder rates ranging from 23.2% to 47.0% with varying doses of retigabine. The most common adverse effects, occurring in greater than 10% of subjects in the clinical trials, include abnormal gait, confusion, dizziness, fatigue, headache, nausea, somnolence, speech disorder, tremor, urinary tract infection, and blurred vision. Conclusions: Retigabine is a promising agent for adjunctive treatment of refractory partialonset seizures.