b'QUVIVIQ (daridorexant) tablets, for oral use, CIV QUVIVIQ (daridorexant) tablets, for oral use, CIVInitial U.S. Approval: 2022 Complex Sleep Behaviors [see Warnings and Precautions] Brief Summary of prescribing information for QUVIVIQ (daridorexant) CIV. Patients with Compromised Respiratory Function [see Warnings andThese highlights do not include all the information needed to use QUVIVIQPrecautions]safely and effectively. See full prescribing information for QUVIVIQ. Clinical Trials ExperienceINDICATIONS AND USAGE Because clinical trials are conducted under widely varying conditions, adverse QUVIVIQ is indicated for the treatment of adult patients with insomnia, characterizedreaction rates observed in clinical trials of a drug cannot be directly compared to by difficulties with sleep onset and/or sleep maintenance. rates in clinical trials of another drug and may not reflect the rates observed in CONTRAINDICATIONS practice.QUVIVIQ is contraindicated: The safety of QUVIVIQ was evaluated in three placebo-controlled clinical studies in patients with narcolepsy. (two 3-month studies of identical design [Study 1 and Study 2], and a 9-monthn patients with a history of hypersensitivity to daridorexant or any components extension study [Study 3]). Study 1 evaluated 50 mg and 25 mg doses of QUVIVIQ, iof QUVIVIQ. Angioedema with pharyngeal involvement has been reportedwhile Study 2 evaluated a 25 mg dose and a 10 mg dose of QUVIVIQ. The 10 mg [see Adverse Reactions]. dose is not an approved dose. A total of 1232 patients (including approximately WARNINGS AND PRECAUTIONS 40% elderly patients [ 65 years old]), received QUVIVIQ 50 mg (N = 308); 25 mg CNS-Depressant Effects and Daytime Impairment (N = 618); or 10 mg (an unapproved dose) (N = 306). A total of 576 patients QUVIVIQ is a central nervous system (CNS) depressant that can impair daytimewere treated with QUVIVIQ for at least 6 months and 331 for at least 12 months.wakefulness even when used as prescribed. CNS-depressant effects may persistMost Common Adverse Reactionsin some patients for up to several days after discontinuing QUVIVIQ. PrescribersThe most common reported adverse reaction (in at least 5% of patients and should advise patients about the potential for next-day somnolence. greater than placebo) during double-blind treatment in Study 1 was headache.Driving ability was impaired in some subjects taking QUVIVIQ 50 mg. The risk ofTable 1 shows adverse reactions that occurred in at least 2% of patients treated daytime impairment is increased if QUVIVIQ is taken with less than a full nightwith QUVIVIQ and more frequently than in patients who received placebo in Study 1.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 activitiesTable 1Adverse Reactions Reported in2% of QUVIVIQ-treated Patientsrequiring complete mental alertness.and Greater than in Placebo-treated Patients in a 3-MonthCo-administration with other CNS depressants (e.g., benzodiazepines, opioids,Placebo-Controlled Study (Study 1)tricyclic antidepressants, alcohol) increases the risk of CNS depression, which can QUVIVIQQUVIVIQPlacebo cause daytime impairment. Dosage adjustments of QUVIVIQ and of concomitant25 mg50 mg CNS depressants may be necessary when administered together because of (N=310)(N=308)(N=309) potentially additive effects. The use of QUVIVIQ with other drugs to treat insomnia% % %is not recommended. Advise patients not to consume alcohol in combinationNervous System Disorderswith QUVIVIQ because co-administration of QUVIVIQ with alcohol resulted in additive effects on psychomotor performance [see Drug Interactions]. Headache* 6 7 5Because QUVIVIQ can cause drowsiness, patients, particularly the elderly, are atSomnolence or fatigue* 6 5 4a higher risk of falls. Dizziness* 2 3 2Worsening of Depression/Suicidal Ideation Gastro-intestinal disordersPatients with psychiatric disorders, including insomnia, are at increased risk of suicide. In primarily depressed patients treated with hypnotics, worsening ofNausea* 0 3 2depression and suicidal thoughts and actions (including completed suicides)*The following terms were combined:have been reported. As with other hypnotics, QUVIVIQ should be administeredHeadache includes: headache, tension headache, migraine, migraine with aura, with caution in patients exhibiting symptoms of depression. Monitoring of suicide head discomfortrisk and protective measures may be required. Somnolence or fatigue includes: somnolence, sedation, fatigue, hypersomnia, lethargy Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-likeDizziness includes: dizziness, vertigo, labyrinthitisSymptoms Nausea includes: nausea, vomiting, procedural nauseaSleep paralysis, an inability to move or speak for up to several minutes duringOther Adverse Reactions Observed During Clinical Trials (Study 1 and Study 2)sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions, can occur with the use of QUVIVIQ [see AdverseOther adverse reactions of 2% frequency but greater than placebo are shown Reactions]. Prescribers should explain the nature of these events to patientsbelow. The following do not include adverse reactions 1) for which a drug cause when prescribing QUVIVIQ. was remote, 2) that were so general as to be uninformative, or 3) that were not Symptoms similar to mild cataplexy have been reported with orexin receptorconsidered to have clinically significant implications. antagonists. Such symptoms can include periods of leg weakness lasting fromSleep paralysis was reported in 0.5% and 0.3% of patients receiving QUVIVIQseconds to a few minutes, can occur either at night or during the day, and may25 mg and 50 mg, respectively, compared to no reports for placebo. not be associated with an identified triggering event (e.g., laughter or surprise) Hypnagogic and hypnopompic hallucinations were reported in 0.6% ofComplex Sleep Behaviors patients receiving QUVIVIQ 25 mg compared to no cases with QUVIVIQ 50 mg Complex sleep behaviors, including sleepwalking, sleep driving, and engagingor placebo.in other activities while not fully awake (e.g., preparing and eating food, makingThe following adverse reactions have been identified during post-approval use phone calls, having sex), have been reported to occur with the use of hypnotics,of QUVIVIQ. Because these reactions are reported voluntarily from a population including orexin receptor antagonists such as QUVIVIQ. These events can occurof uncertain size, it is not always possible to reliably estimate their frequency or in hypnotic-nave as well as in hypnotic-experienced persons. Patients usually doestablish a causal relationship to drug exposure.not remember these events. Complex sleep behaviors may occur following thePsychiatric disorders: Nightmares or abnormal dreamsfirst or any subsequent use of hypnotics, such as QUVIVIQ, with or without theImmune system disorders: Hypersensitivity (including angioedema, rash, urticaria)concomitant use of alcohol and other CNS depressants [see Drug Interactions]. Discontinue QUVIVIQ immediately if a patient experiences a complex sleep behavior. DRUG INTERACTIONSPatients with Compromised Respiratory Function Effects of Other Drugs on QUVIVIQThe effects of QUVIVIQ on respiratory function should be considered if prescribedTable 2 describes clinically significant drug interactions where the concomitant to patients with compromised respiratory function. QUVIVIQ has not been studieduse of other drugs affects QUVIVIQ.in patients with moderate OSA requiring CPAP or severe OSA. QUVIVIQ has notTable 2Effects of Other Drugs on QUVIVIQ been studied in patients with severe COPD [see Use in Specific Populations]. Strong or Moderate CYP3A4 InhibitorsNeed to Evaluate for Co-morbid Diagnoses Because sleep disturbances may be the presenting manifestation of a medicalClinicalConcomitant use with a strong or moderate CYP3A4 inhibitor and/or psychiatric disorder, treatment of insomnia should be initiated only afterImplications: increases exposure to daridorexant, which may increase the careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 daysrisk of QUVIVIQ adverse reactions.of treatment may indicate the presence of a primary psychiatric and/or medicalPrevention orThe recommended dose of QUVIVIQ is 25 mg when used with illness that should be evaluated. Worsening of insomnia or the emergence ofManagement: a moderate CYP3A4 inhibitor.new cognitive or behavioral abnormalities may be the result of an unrecognizedConcomitant use of QUVIVIQ with a strong inhibitor of CYP3A4 underlying psychiatric or medical disorder and can emerge during the course ofis not recommended.treatment with sleep-promoting drugs such as QUVIVIQ.ADVERSE REACTIONS Strong and Moderate CYP3A4 InducersThe following are discussed in detail in other sections of the labeling: ClinicalConcomitant use with a strong or moderate CYP3A4 inducerCNS-Depressant Effects and Daytime Impairment [see Warnings andImplications: decreases exposure to daridorexant, which may reduce the efficacy of QUVIVIQ.Precautions]Worsening of Depression/Suicidal Ideation [see Warnings and Precautions] Prevention orConcomitant use of QUVIVIQ with a strong or moderate inducerSleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy- Management: of CYP3A4 is not recommended. like Symptoms [see Warnings and Precautions] (continued)'