Profile of suvorexant in the management of insomnia

Abstract

Suvorexant, approved in late 2014 in the United States and Japan for the treatment of insomnia characterized by difficulty achieving and/or maintaining sleep, is a dual orexin receptor antagonist and the first drug in its class to reach the market. Its development followed from the 1998 discovery of orexins (also called hypocretins), excitatory neuropeptides originating from neurons in the hypothalamus involved in regulation of sleep and wake, feeding behavior and energy regulation, motor activity, and reward-seeking behavior. Suvorexant objectively improves sleep, shortening the time to achieve persistent sleep and reducing wake after sleep onset, although at approved doses (≤20 mg) the benefit was subjectively assessed as modest. Its half-life of 12 hours is relatively long for a modern hypnotic; however, at approved doses (≤20 mg) next-day sedation and driving impairment were much less apparent than at higher doses. Suvorexant is metabolized by the hepatic CYP3A system and should be avoided in combination with strong CYP3A inhibitors. Drug levels are higher in women and obese people; hence, dosing should be conservative in obese women. Administration with food delays drug absorption and is not advised. No dose adjustment is needed for advanced age, renal impairment, or mild-to-moderate hepatic impairment. Suvorexant in contraindicated in narcolepsy and has not been studied in children. In alignment with the changes begun in 2013 in the labeling of other hypnotics, the United States Food and Drug Administration advises that the lowest dose effective to treat symptoms be used and that patients be advised of the possibility of next-day impairment in function, including driving. Infrequent but notable side effects included abnormal dreams, sleep paralysis, and suicidal ideation that were dose-related and reported to be mild. Given its mechanism of action, cataplexy and rapid eye movement (REM) sleep behavior disorder could potentially occur in some patients taking this medication.