Comparative Pharmacology of the 3 Marketed Dual Orexin Antagonists—Daridorexant, Lemborexant, and Suvorexant—Part 2. Principal Drug Metabolizing Enzyme, Drug-Drug Interactions, and Effects of Liver and Renal Impairment on Metabolism

Abstract

This column is the second in a 2-part series presenting the comparative pharmacology of the 3 Food and Drug Administration–approved dual orexin receptor antagonists, daridorexant, lemborexant, and suvorexant. Both of the columns in this series emphasize the pharmacokinetics of these drugs as they are relevant to their use as sleep medications. Although other classes of sleep medications are not discussed, the same pharmacokinetic principles also apply to them in terms of endeavoring to match the pharmacokinetics of an agent to the individual’s usual sleep cycle. This second column in the series focuses on the metabolism of each of the 3 drugs by the cytochrome P450 enzyme CYP3A, guidance for using these agents in combination with drugs that are CYP3A inhibitors or inducers, and how to adjust dosing in patients with comorbid conditions such as hepatic or renal impairment.