Retrospective assessment of toxicity following exposure to Orexin pathway modulators modafinil and suvorexant

Abstract Orexin A and B and their receptors OX1R and OX2R modulate human sleep/wakefulness cycles, energy homeostasis, and behavior. Modafinil and suvorexant either directly or indirectly manipulate the orexin neuro-excitatory system. As such they are prototypes for modulation of this pathway and can be used to anticipate the clinical effects of exposure to the emerging drug class. We queried the National Poison Data System for exposures to both between 2005 and 2017. Single-substance exposures followed to a known outcome were included. Severity of outcome, clinical effects, healthcare facility utilization, and reason for exposure were assessed. 1616 modafinil and 83 suvorexant exposures were included. No deaths occurred. No major effects were noted in suvorexant exposures while 0.9% of exposures to modafinil resulted in major effects. Exposure to modafinil commonly resulted in stimulant-type effects: agitation (2.8%), tachycardia (1%), and hypertension (1%). Suvorexant resulted in sedation in 26.1% of exposures. Vomiting (15.9%) was also noted in suvorexant exposures. Both modafinil and suvorexant appear well-tolerated following exposure