Efficacy of Retigabine in Adjunctive Treatment of Partial Onset Seizures in Adults

Abstract

ObjectiveTo evaluate efficacy and tolerability of retigabine (ezogabine, US adopted name) in the adjunctive treatment of partial-onset seizures in adults. Retigabine is the first anticonvulsant in its class, decreasing neuronal excitability by opening voltage-gated potassium channels.MethodsMEDLINE and EMBASE were systematically searched using search terms retigabine and ezogabine for randomized controlled trials published from 1980 through August 17, 2013. Additionally, articles relating to pharmacology, pharmacokinetics, tolerability and interactions were examined for inclusion. Published abstracts and websites of the Food and Drug Administration and European Medication Agency were reviewed for additional relevant information.ResultsOne phase IIb and two phase III trials were identified. Retigabine has been reported to have dose dependent efficacy in adjunctive treatment of resistant partial-onset seizures in adults in doses of 600, 900 and 1200 mg/day. Similar to other anticonvulsants, the most common adverse events were central nervous system related. Retigabine has several unique adverse events compared to other anticonvulsants: urinary retention and, with extended use, pigment changes to the skin and retina. Retigabine is metabolized by glucuronidation and acetylation. There are few drug interactions with retigabine.ConclusionsRetigabine has been shown to have efficacy when used as adjunctive therapy in partial-onset seizures. It has a novel mechanism of action, activation of voltage-gated potassium channels. It has less drug interactions than many other anticonvulsants because it is not metabolized through the P-450 system. Its place in therapy has yet to be determined, especially with recent reports of pigment discoloration of skin and the retina with extended use.

Efficacy and safety of retigabine/ezogabine as adjunctive therapy in adult Asian patients with drug-resistant partial-onset seizures: A randomized, placebo-controlled Phase III study

“…Treatment-related retinal pigmentation was not reported in any patients who underwent an eye examination. This is likely to have been due to the brief exposure to treatment, as retinal pigmentation has been observed generally after an extended course of treatment [10]. No patients discontinued owing to abnormal retinal pigmentation.…”

Early and effective treatment of KCNQ2 encephalopathy

“…25 Unfortunately, it has recently been associated with the side effect of blue discoloration in the digits and retina, which will delay trials of it or await the development of an analog with a safer profile. 26 We suggest that CBZ and PHT are considered as first-line therapy for SE in neonates with KCNQ2 encephalopathy. With the ready availability of intravenous administration and blood level monitoring, the efficacy and substantial experience to date, PHT is ideal for SE in this disorder.…”

“…Retigabine acts as a neuronal KCNQ/kv7K channel opener and may provide a targeted treatment for KCNQ2 encephalopathy . Unfortunately, it has recently been associated with the side effect of blue discoloration in the digits and retina, which will delay trials of it or await the development of an analog with a safer profile …”

Kv7 channels in the nucleus accumbens are altered by chronic drinking and are targets for reducing alcohol consumption

“…Activation of Kv7 channels serves as a brake on neuronal excitability during sustained or repetitive firing. Positive modulation of Kv7 channels effectively reduces seizures in humans and in multiple animal models of epilepsy (Splinter, 2013). Although there are several Kv7 channel positive modulators, the best characterized is retigabine (ezogabine), an FDA-approved drug for the treatment of partial onset seizures.…”