b'QUVIVIQ (daridorexant) tablets, for oral use, CIVQUVIVIQ (daridorexant) tablets, for oral use, CIV Initial U.S. Approval: 2022Clinical Trials Experience 10 Summary of prescribing Information for QUVIVIQ (daridorexant) CIV.Because clinical trials are conducted under widely varying conditions, adverse Brief INDICATIONS AND USAGEreaction rates observed in clinical trials of a drug cannot be directly compared QUVIVIQ is indicated for the treatment of adult patients with insomnia, characterizedto rates in clinical trials of another drug and may not reflect the rates observed by difficulties with sleep onset and/or sleep maintenance [see Clinical Studies inin practice. the full prescribing information].The safety of QUVIVIQ was evaluated in three placebo-controlled clinical studiesCONTRAINDICATIONS(two 3-month studies of identical design [Study 1 and Study 2], and a 9-month QUVIVIQ is contraindicated in patients with narcolepsy.extension study [Study 3]). Study 1 evaluated 50 mg and 25 mg doses of WARNINGS AND PRECAUTIONSQUVIVIQ, while Study 2 evaluated a 25 mg dose and a 10 mg dose of QUVIVIQ. CNS-Depressant Effects and Daytime ImpairmentThe 10 mg dose is not an approved dose. A total of 1232 patients (including QUVIVIQ is a central nervous system (CNS) depressant that can impair daytimeapproximately 40% elderly patients [ 65 years old]), received QUVIVIQ 50 mg wakefulness even when used as prescribed. CNS-depressant effects may persist(N = 308); 25 mg (N = 618); or 10 mg (an unapproved dose) (N = 306). A total in some patients for up to several days after discontinuing QUVIVIQ. Prescribersof 576 patients were treated with QUVIVIQ for at least 6 months and 331 for at should advise patients about the potential for next-day somnolence.least 12 months. Driving ability was impaired in some subjects taking QUVIVIQ 50 mg [seeMost Common Adverse Reactions Clinical Studies in the full prescribing information]. The risk of daytimeThe most common reported adverse reaction (in at least 5% of patients and impairment is increased if QUVIVIQ is taken with less than a full night of sleepgreater than placebo) during double-blind treatment in Study 1 was headache. remaining or if a higher than recommended dose is taken [see Dosage andTable 1 shows adverse reactions that occurred in at least 2% of patients treated with Administration in the full prescribing information]. If QUVIVIQ is taken in theseQUVIVIQ and more frequently than in patients who received placebo in Study 1. circumstances, caution patients against driving and other activities requiringTable 1Adverse Reactions Reported in2% of QUVIVIQ-treated Patients complete mental alertness.and Greater than in Placebo-treated Patients in a 3-Month Placebo-Co-administration with other CNS depressants (e.g., benzodiazepines, opioids,Controlled Study (Study 1) tricyclic antidepressants, alcohol) increases the risk of CNS depression, whichQUVIVIQQUVIVIQPlacebo can cause daytime impairment. Dosage adjustments of QUVIVIQ and of25 mg50 mgconcomitant CNS depressants may be necessary when administered together(N=310)(N=308)(N=309) 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 alcoholNervous System Disordersresulted 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 IdeationGastro-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 ofhead discomfortsuicide risk and protective measures may be required.Somnolence or fatigue includes: somnolence, sedation, fatigue, hypersomnia, Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-likelethargy SymptomsDizziness includes: dizziness, vertigo, labyrinthitisSleep paralysis, an inability to move or speak for up to several minutes duringNausea includes: nausea, vomiting, procedural nauseasleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including Other Adverse Reactions Observed During Clinical Trials (Study 1 and Study 2) 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 from Sleep paralysis was reported in 0.5% and 0.3% of patients receiving QUVIVIQ seconds 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% of patients Complex Sleep Behaviorsreceiving QUVIVIQ 25 mg compared to no cases with QUVIVIQ 50 mg or placebo. Complex sleep behaviors, including sleepwalking, sleep driving, and engaging inPost-Marketing Experience 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 usuallyestablish a causal relationship to drug exposure. do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of hypnotics, such as QUVIVIQ, with or withoutPsychiatric disorders: Abnormal dreams or nightmares the concomitant use of alcohol and other CNS depressants [see Drug Interactions].Immune system disorders: Hypersensitivity (such as rash, urticaria) Discontinue QUVIVIQ immediately if a patient experiences a complex sleep behavior.DRUG INTERACTIONS Patients with Compromised Respiratory FunctionDrugs Having Clinically Important Interactions with QUVIVIQThe effects of QUVIVIQ on respiratory function should be considered if prescribedTable 2Clinically Important Drug Interactions with QUVIVIQ to patients with compromised respiratory function. QUVIVIQ has not been studied in patients with moderate OSA requiring CPAP or severe OSA. QUVIVIQStrong or Moderate CYP3A4 Inhibitorshas not been studied in patients with severe COPD [see Use in Specific Populations].ClinicalConcomitant use with a strong or moderate CYP3A4 inhibitor Need to Evaluate for Co-morbid DiagnosesImplications: increases exposure to daridorexant [see Clinical Pharmacology Because sleep disturbances may be the presenting manifestation of a medicalin the full prescribing information], which may increase the risk and/or psychiatric disorder, treatment of insomnia should be initiated only afterof QUVIVIQ adverse reactions.careful evaluation of the patient. The failure of insomnia to remit after 7 to Prevention orThe recommended dose of QUVIVIQ is 25 mg when used with a 10 days of treatment may indicate the presence of a primary psychiatric and/orManagement: moderate CYP3A4 inhibitor [see Dosage and Administration in medical illness that should be evaluated. Worsening of insomnia or thethe full prescribing information].emergence of new cognitive or behavioral abnormalities may be the result of anConcomitant use of QUVIVIQ with a strong inhibitor of CYP3A4 unrecognized underlying psychiatric or medical disorder and can emerge duringis not recommended [see Dosage and Administration in the full the course of treatment with sleep-promoting drugs such as QUVIVIQ.prescribing information].ADVERSE REACTIONSStrong and Moderate CYP3A4 InducersThe following are discussed in detail in other sections of the labeling:CNS-Depressant Effects and Daytime Impairment [see Warnings andClinicalConcomitant use with a strong or moderate CYP3A4 inducer Precautions]Implications: decreases exposure to daridorexant [see Clinical PharmacologyWorsening of Depression/Suicidal Ideation [see Warnings and Precautions]in the full prescribing information], which may reduce theSleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-likeefficacy of QUVIVIQ.Symptoms [see Warnings and Precautions]Prevention orConcomitant use of QUVIVIQ with a strong or moderate inducerComplex Sleep Behaviors [see Warnings and Precautions]Management: of CYP3A4 is not recommended [see Dosage and AdministrationPatients with Compromised Respiratory Function [see Warnings andin the full prescribing information].Precautions](continued)'