QUVIVIQ contains daridorexant, an orexin receptor antagonist, present as daridorexant hydrochloride salt. The chemical name of daridorexant hydrochloride is (S)-(2-(5-chloro-4-methyl-1 H -benzo[ d ]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2 H -1,2,3-triazol-2-yl)phenyl)methanone hydrochloride. The molecular formula is C 23 H 23 N 6 O 2 Cl * HCl. The molecular weight is 487.38 g/mol. The structural formula is: Daridorexant hydrochloride is a white to light yellowish powder that is very slightly soluble in water. QUVIVIQ tablets are intended for oral administration. Each film-coated tablet contains daridorexant 25 mg or 50 mg, equivalent to 27 mg or 54 mg of daridorexant hydrochloride, respectively. The inactive ingredients are croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, povidone, and silicon dioxide. In addition, the film coating contains the following inactive ingredients: glycerin, hypromellose, iron oxide black, iron oxide red, microcrystalline cellulose, talc, titanium dioxide, and, in the 50 mg tablet only, iron oxide yellow. Chemical Structure

QUVIVIQ is indicated for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance . QUVIVIQ is an orexin receptor antagonist indicated for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance.

QUVIVIQ (daridorexant) tablets are available as: 25 mg: light purple, arc-triangle shaped, film-coated tablet debossed with "25" on one side and "i" (Idorsia logo) on the other side, containing 25 mg daridorexant. 50 mg: light orange, arc-triangle shaped, film-coated tablet debossed with "50" on one side and "i" (Idorsia logo) on the other side, containing 50 mg daridorexant. Tablets: 25 mg, 50 mg.

The recommended dosage is 25 mg to 50 mg once per night, taken orally within 30 minutes before going to bed, with at least 7 hours remaining prior to planned awakening. Time to sleep onset may be delayed if taken with or soon after a meal. Hepatic Impairment: Moderate hepatic impairment: Maximum recommended dosage is 25 mg no more than once per night. Severe hepatic impairment: Not recommended

Recommended Dosage The recommended dosage range is 25 mg to 50 mg of QUVIVIQ taken orally no more than once per night within 30 minutes of going to bed (with at least 7 hours remaining prior to planned awakening). Time to sleep onset may be delayed if taken with or soon after a meal

Dosage Recommendations for Concomitant Use with CYP3A4 Inhibitors or CYP3A4 Inducers Co-administration with Strong CYP3A4 Inhibitors Avoid concomitant use of QUVIVIQ with strong inhibitors of CYP3A4 . Co-administration with Moderate CYP3A4 Inhibitors The recommended dosage of QUVIVIQ is 25 mg no more than once per night when used with moderate inhibitors of CYP3A4 . Co-administration with Strong or Moderate CYP3A4 Inducers Avoid concomitant use of QUVIVIQ with strong or moderate CYP3A4 inducers

Dosage Recommendations for Patients with Hepatic Impairment The maximum recommended dosage in patients with moderate hepatic impairment (Child-Pugh score 7–9) is 25 mg of QUVIVIQ no more than once per night . QUVIVIQ is not recommended in patients with severe hepatic impairment (Child-Pugh score ≥ 10) .

CNS-Depressant Effects and Daytime Impairment: Impairs alertness and motor coordination including morning impairment. Risk increases when used with other central nervous system (CNS) depressants. For patients taking QUVIVIQ, caution against next-day driving and other activities requiring complete mental alertness. Worsening of Depression/Suicidal Ideation: Worsening of depression or suicidal thinking may occur. Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms: May occur with use of QUVIVIQ. Complex Sleep Behaviors: Behaviors including sleepwalking, sleep driving, and engaging in other activities while not fully awake may occur. Discontinue immediately if complex sleep behavior occurs. Compromised Respiratory Function: Effect on respiratory function should be considered. Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia persists after 7 to 10 days. 5.1 CNS-Depressant Effects and Daytime Impairment QUVIVIQ is a central nervous system (CNS) depressant that can impair daytime wakefulness even when used as prescribed. CNS-depressant effects may persist in some patients for up to several days after discontinuing QUVIVIQ. Prescribers should advise patients about the potential for next-day somnolence. Driving ability was impaired in some subjects taking QUVIVIQ 50 mg . The risk of daytime impairment is increased if QUVIVIQ is taken with less than a full night of sleep remaining or if a higher than recommended dose is taken . If QUVIVIQ is taken in these circumstances, caution patients against driving and other activities requiring complete mental alertness. Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime impairment. Dosage adjustments of QUVIVIQ and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of QUVIVIQ with other drugs to treat insomnia is not recommended . Advise patients not to consume alcohol in combination with QUVIVIQ because co-administration of QUVIVIQ with alcohol resulted in additive effects on psychomotor performance . Because QUVIVIQ can cause drowsiness, patients, particularly the elderly, are at a higher risk of falls

Worsening of Depression/Suicidal Ideation Patients with psychiatric disorders, including insomnia, are at increased risk of suicide. In primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions (including completed suicides) have been reported. As with other hypnotics, QUVIVIQ should be administered with caution in patients exhibiting symptoms of depression. Monitoring of suicide risk and protective measures may be required

Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-like Symptoms 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 with the use of QUVIVIQ . Prescribers should explain the nature of these events to patients when prescribing QUVIVIQ. Symptoms similar to mild cataplexy have been reported with orexin receptor antagonists. Such symptoms can include periods of leg weakness lasting from seconds to a few minutes, can occur either at night or during the day, and may not be associated with an identified triggering event (e.g., laughter or surprise)

Complex Sleep Behaviors Complex sleep behaviors, including sleepwalking, sleep driving, and engaging in other activities while not fully awake (e.g., preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics, including orexin receptor antagonists such as QUVIVIQ. These events can occur in hypnotic-naïve as well as in hypnotic-experienced persons. Patients usually do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of hypnotics, such as QUVIVIQ, with or without the concomitant use of alcohol and other CNS depressants . Discontinue QUVIVIQ immediately if a patient experiences a complex sleep behavior

Patients with Compromised Respiratory Function QUVIVIQ has been studied in mild to severe OSA not using CPAP, and in patients with moderate COPD. The effects of QUVIVIQ on respiratory function should be considered if prescribed to patients with compromised respiratory function. QUVIVIQ has not been studied in patients with mild or severe COPD

Need to Evaluate for Co-morbid Diagnoses Because sleep disturbances may be the presenting manifestation of a medical and/or psychiatric disorder, treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an unrecognized underlying psychiatric or medical disorder and can emerge during the course of treatment with sleep-promoting drugs such as QUVIVIQ.

Strong CYP3A4 inhibitors: Avoid concomitant use. Moderate CYP3A4 inhibitors: Maximum recommended dose is 25 mg. Moderate or Strong CYP3A4 inducers: Avoid concomitant use

Effects of Other Drugs on QUVIVIQ Table 2 describes clinically significant drug interactions where the concomitant use of other drugs affects QUVIVIQ. Table 2 Effects of Other Drugs on QUVIVIQ Strong or Moderate CYP3A4 Inhibitors Clinical Implications: Concomitant use with a strong or moderate CYP3A4 inhibitor increases exposure to daridorexant , which may increase the risk of QUVIVIQ adverse reactions. Prevention or Management: The recommended dose of QUVIVIQ is 25 mg when used with a moderate CYP3A4 inhibitor . Concomitant use of QUVIVIQ with a strong inhibitor of CYP3A4 is not recommended . Strong and Moderate CYP3A4 Inducers Clinical Implications: Concomitant use with a strong or moderate CYP3A4 inducer decreases exposure to daridorexant , which may reduce the efficacy of QUVIVIQ. Prevention or Management: Concomitant use of QUVIVIQ with a strong or moderate inducer of CYP3A4 is not recommended . Alcohol and Other CNS Depressants Clinical Implications: Concomitant use of alcohol or other CNS depressants with QUVIVIQ may lead to additive impairment of psychomotor performance and risk of CNS depression . Prevention or Management: Avoid alcohol consumption with QUVIVIQ . Use with caution in patients receiving CNS depressants. Consider dose adjustment of QUVIVIQ and/or the CNS depressant(s) if used concomitantly

Effects of QUVIVIQ on Other Drugs Table 3 describes clinically significant drug interactions where the concomitant use of QUVIVIQ affects other drugs. Table 3 Effects of QUVIVIQ on Other Drugs CYP3A4 Substrates Clinical Implications: Concomitant use of QUVIVIQ with CYP3A4 substrates increases the exposure to CYP3A4 substrate . Prevention or Management: Use with caution in patients receiving CYP3A4 substrates with narrow therapeutic index. P-gp Substrates Clinical Implications: Concomitant use of QUVIVIQ with P-gp substrates increases the exposure to P-gp substrate . Prevention or Management: Use with caution in patients receiving P-gp substrates with a narrow therapeutic index.