of psychomotor performance and cause daytime impairment. triazolamMonitor Closely (1)triazolam and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. trifluoperazineMonitor Closely (1)trifluoperazine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. trimethobenzamideMonitor Closely (1)trimethobenzamide and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. trimipramineMonitor Closely (1)trimipramine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. triprolidineMonitor Closely (1)triprolidine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. valerianMonitor Closely (1)valerian and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. valproic acidMonitor Closely (1)valproic acid and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. verapamilMonitor Closely (1)verapamil will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.vigabatrinMonitor Closely (1)vigabatrin and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. vilazodoneMonitor Closely (1)vilazodone and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. voriconazoleSerious - Use Alternative (1)voriconazole will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.vortioxetineMonitor Closely (1)vortioxetine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. voxelotorMonitor Closely (1)voxelotor will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.zaleplonMonitor Closely (1)zaleplon and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. ziconotideMonitor Closely (1)ziconotide and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. ziprasidoneMonitor Closely (1)ziprasidone and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. zolpidemMonitor Closely (1)zolpidem and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. zonisamideMonitor Closely (1)zonisamide and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. 1-10% Headache (6-7%) Somnolence or fatigue (5-6%) Dizziness (2-3%) Nausea (3%) <1% Hypnagogic and hypnopompic hallucinations (0.6%) Sleep paralysis (0.3-0.5%) Contraindications Narcolepsy Cautions Worsening depression or suicidal ideation may occur; caution in patients exhibiting symptoms of depression; monitor signs and symptoms of suicide, and provide protective measures Sleep paralysis (an inability to move or speak for up to several minutes during sleep-wake transitions) and hypnagogic/hypnopompic hallucinations (including vivid and disturbing perceptions) can occur; explain the nature of these events when prescribing Cognitive and behavioral changes (eg, amnesia, anxiety, hallucinations, other neuropsychiatric symptoms) reported with hypnotics; “sleep driving” and other complex behaviors (eg, preparing and eating food, making phone calls, having sex), with amnesia for the event, have been reported; discontinue therapy immediately if complex sleep behavior experienced Consider effects on respiratory function if prescribed to patients with compromised respiratory function; not studied in patients with moderate obstructive sleep apnea (OSA) requiring continuous positive airway pressure, severe OSA, or severe chronic obstructive pulmonary disease Reevaluate patients for comorbid conditions if insomnia persists after 7-10 days of treatment CNS depressant effects May impair daytime wakefulness, even when used as prescribed CNS-depressant effects may persist up to several days after discontinuing Advise patients of potential for next-day somnolence Increased risk of daytime impairment may occur if dose taken with less than a full night of sleep or with higher than recommended dose Coadministration with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases risk of CNS depression, which can cause daytime impairment Dosage adjustments of daridorexant and concomitant CNS depressants may be necessary when administered together because of potentially additive effects Not recommended for concomitant use with other drugs for insomnia Alcohol consumption during therapy not recommended Patients, especially elderly individuals, may be at higher risk of falls owing to potential for drowsiness Symptoms similar to mild cataplexy reported with orexin receptor antagonists; suchsymptoms can include periods of leg weakness lasting from seconds to few minutes, can occureither at night or during day, and may not be associated with an identified triggering event (eg, laughter or surprise) Drug interaction overview Substrate of CYP3A4 Strong or moderate CYP3A4 inhibitors Strong CYP3A4 inhibitors: Avoid coadministration Moderate CYP3A4 inhibitors: Not to exceed 25 mg/night Strong or moderate CYP3A4 inhibitors may increase exposure and risk of daridorexant adverse reactions Strong or moderate CYP3A4 inducers Not recommended Strong or moderate CYP3A4 inducers may decrease exposure and efficacy of daridorexant Alcohol and other CNS depressants Avoid alcohol consumption Use with caution; consider dosage adjustment of both daridorexant and/or CNS depressants Alcohol and other CNS depressants may lead to additive impairment of psychomotor skills and risk of CNS depression Pregnancy No data are available on use in pregnant females to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes Pregnancy exposure registry Monitors pregnancy outcomes in females exposed to drug during pregnancy Encourage patients to call Idorsia Pharmaceutical Ltd. at 1-833-400-9611 Animal data In pregnant rats, orally administered doses up to 300 mg/kg/day during organogenesis did not cause maternal or embryofetal toxicities or fetal malformations In pregnant rabbits, orally administered doses up to 120 mg/kg/day during organogenesis did not cause fetal toxicities or malformations; maternal toxicities (eg, decreased weight gain, decreased food consumption) reported Lactation There are no data on presence of drug in human milk, effects on breastfed infants, or effects on milk production Drug and metabolite are present in rat milk; when drug is present in animal milk, it is likely that the drug will be present in human milk Pregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Dual orexin antagonist (DORA) Orexins are neuropeptides that regulate the sleep-wake cycle; orexins promote wakefulness by binding G-protein-coupled receptors, OX1R and OX2R Blocking neuropeptides from binding to OX1R and OX2R is believed to suppress wake drive Absorption Peak plasma time: 1-2 hr Bioavailability: 62% Effects of food Healthy adults: High-fat and high-calorie meal delay peak plasma time by 1.3 hr and decreased peak plasma concentration by 16%; no effect on AUC Distribution Vd: 31 L Protein bound: 99.7% Metabolism Extensively metabolized by CYP3A4 (89%) Other CYP enzymes contribute to <3% of daridorexant metabolic clearance Elimination Half-life: 8 hr Excretion (primarily as metabolites, traces of parent drug): 57% (feces); 28% (urine) Oral Administration Take orally within 30 min before going to bed, with at least 7 hr remaining before planned awakening Time to sleep onset may be delayed if taken with or soon after a meal Avoid alcohol consumption during therapy Storage Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription. QL Quantity Limits Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered. ST Step Therapy Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription. OR Other Restrictions Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription. 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