Safety of dual orexin receptor antagonists: a real-world pharmacovigilance study

BACKGROUND: Dual orexin receptor antagonists (DORAs) are widely used for treating insomnia. However, real-world data on the adverse events (AEs) induced by DORAs are lacking. METHODS: Data related to daridorexant, suvorexant, and lemborexant were collected from the US Food and Drug Administration Adverse Event Reporting System between the first quarter of 2022 and the third quarter of 2024. Two established signal quantification methods, the reporting odds ratios and proportional reporting ratios, were applied. RESULTS: A total of 2665 reports on daridorexant (1738, 65.22%), suvorexant (667, 25.03%), and lemborexant (260, 9.75%) were obtained. 24 targeted systems for daridorexant, 24 for suvorexant, and 25 for lemborexant were involved. We analyzed the top 30 preferred terms (PTs) that met both algorithm criteria and identified 69 PTs. The highest signal of strength of PT was sleep paralysis for daridorexant and lemborexant, and abnormal sleep-related event for suvorexant. The most frequent PT was somnolence for lemborexant (30, 11.54%) and insomnia for daridorexant (252, 14.50%) and suvorexant (62, 9.30%) within the top 30 PTs. CONCLUSION: The analysis of disproportionality signals may prompt increased awareness of toxicities for DORAs. The results of serious reports and dosage of drugs provided supporting evidence for clinicians to manage AEs.