Gabapentin Enacarbil: A Review in Restless Legs Syndrome

Gabapentin enacarbil is an extended-release prodrug of gabapentin that is approved in the USA (Horizant®) and Japan (Regnite®) for the treatment of moderate to severe primary restless legs syndrome (RLS) in adults [featured indication]. This article summarizes pharmacological, efficacy and tolerability data relevant to the use of oral gabapentin enacarbil in this indication. In double-blind, multicentre trials, treatment with gabapentin enacarbil 600 mg/day for 12 weeks significantly improved the symptoms of moderate to severe primary RLS in adults. Gabapentin enacarbil also significantly improved RLS pain scores and generally improved sleep and mood outcomes. These data are supported by retrospective pooled analyses of three of these trials (XP081, PIVOT RLS I and PIVOT RLS II), with gabapentin enacarbil generally improving symptoms irrespective of disease severity, associated sleep disturbance or prior dopamine agonist use. Responses to gabapentin enacarbil were sustained in longer-term trials, with lower relapse rates in gabapentin enacarbil than placebo recipients in a longer-term maintenance study. Overall, in short and longer-term trials, relatively few patients discontinued treatment, adverse events were mostly mild to moderate in severity, and somnolence/sedation and dizziness were the most commonly reported adverse events. Notably, there were no reports of augmentation or QT-interval prolongation. Gabapentin enacarbil is an important agent for the treatment of adults with moderate to severe primary RLS.