Dichlorphenamide: A Review in Primary Periodic Paralyses.

Oral dichlorphenamide (Keveyis™) is a carbonic anhydrase inhibitor that is approved in the USA for the treatment of primary hyperkalaemic and hypokalaemic periodic paralyses and related variants. The efficacy and safety of dichlorphenamide in patients with primary periodic paralyses have been evaluated in four 9-week, randomized, double-blind, placebo-controlled, phase III trials [two parallel-group trials (HOP and HYP) and two crossover trials]. In two trials in patients with hypokalaemic periodic paralysis, dichlorphenamide was associated with a significantly (eightfold) lower paralytic attack rate and fewer patients with acute intolerable worsening compared with placebo. In two trials in patients with hyperkalaemic periodic paralysis, the attack rate was lower with dichlorphenamide than placebo, with this comparison reaching statistical significance in one trial (crossover) but not the other (HYP), although the attack rate was approximately fivefold lower with dichlorphenamide than placebo in the HYP trial. In 52-week, open-label extensions of the HOP and HYP trials, dichlorphenamide provided sustained efficacy in patients with hypokalaemic or hyperkalaemic periodic paralysis. Dichlorphenamide was generally well tolerated in all four phase III trials and during the extension trials; the most common adverse events were paraesthesia, cognitive disorders and dysgeusia. As the first agent to be approved in the USA for this indication, dichlorphenamide is a valuable treatment option for patients with primary hyperkalaemic or hypokalaemic periodic paralysis.