Retigabine: fewer drug interactions

There are already about a dozen antiepileptic drugs with acceptable harm-benefit balances that can be used in combination therapy for adult patients whose partial epilepsy is not adequately controlled by successive single-agent regimens. Retigabine (Trobalt, GlaxoSmithKline) has now been authorised in the European Union in this indication. Clinical evaluation is based on 3 double-blind randomised controlled trials in which either retigabine or placebo was added to an ineffective ongoing treatment. An additional 30% of patients treated with retigabine (in absolute numbers) had at least a 50% reduction in the monthly frequency of seizures. This translates to approximately 50% of patients with a reduced seizure rate as compared with about 20% of patients on placebo. Based on indirect comparisons, which must be interpreted with care, this efficacy seems similar to that of other antiepileptic drugs. Retigabine shares several adverse effects with other antiepileptic drugs, especially neuropsychiatric disorders. Retigabine can also cause urinary disorders (5%), psychotic disorders (about 6%) and urolithiasis. It also appears to prolong the QT interval. Retigabine does not interfere with major cytochrome P450 isoenzymes or with P-glycoprotein-mediated drug transport. About 30% of the ingested dose is excreted unchanged in urine. The risk of pharmacokinetic interactions is low in patients with normal renal function. In practice, retigabine is another option for second-line combination therapy in patients at high risk of drug interactions.