Safety of Dual Orexin Receptor Antagonist Daridorexant: A Disproportionality Analysis of Publicly Available FAERS Data.

ABSTRACT

Daridorexant (dari), as the first dual orexin receptor antagonist (DORA) marketed in Europe, offers a novel therapeutic approach to insomnia. However, data regarding its real-world safety are scarce. Thus, this study was aimed at assessing its safety profile using a large-scale pharmacovigilance database. Dari-related adverse drug reaction (ADR) reports from the Food and Drug Administration Adverse Event Reporting System were scrutinized, and ADRs were selected using reporting odds ratio (ROR) as a measure of disproportionality. Frequencies of events related to dari were compared to all other drugs (reference group, RG1) and only to other DORAs (RG2). Only significant disproportionalities to both RGs were evaluated in-depth. A total of 845 dari-related reports were selected; nightmares (n = 146; dari vs. RG1 ROR = 113.74; 95%CI [95.13, 136]; dari vs. RG2 ROR = 2.35; 95 CI% [1.93, 2.85]), depression (n = 22; dari vs. RG1 2.13; [1.39, 3.25]; dari vs. RG2 ROR = 2.31; 95 CI% [1.45, 3.67]), and hangover (n = 20; dari vs. RG1 ROR = 127.92; 95 CI% [81.98, 199.62]; and dari vs. RG2 3.38; [2.04, 5.61]) were considered as safety signals. These data provide valuable insights into the real-world safety profile of daridorexant, supporting the existence of safety signals related to nightmares, depression, and hangovers.