b'QUVIVIQ (daridorexant) tablets, for oral use, CIVQUVIVIQ (daridorexant) tablets, for oral use, CIV Initial U.S. Approval: 2022Clinical Trials Experience Brief Summary of prescribing Information for QUVIVIQ (daridorexant) CIV.Because clinical trials are conducted under widely varying conditions, adverse reaction INDICATIONS AND USAGErates observed in clinical trials of a drug cannot be directly compared to rates in clinical QUVIVIQ is indicated for the treatment of adult patients with insomnia, characterized bytrials of another drug and may not reflect the rates observed in practice. difficulties with sleep onset and/or sleep maintenance [see Clinical Studies in the fullThe safety of QUVIVIQ was evaluated in three placebo-controlled clinical studiesprescribing information].(two 3-month studies of identical design [Study 1 and Study 2], and a 9-month extension CONTRAINDICATIONSstudy [Study 3]). Study 1 evaluated 50 mg and 25 mg doses of QUVIVIQ, while Study 2 QUVIVIQ is contraindicated in patients with narcolepsy.evaluated a 25 mg dose and a 10 mg dose of QUVIVIQ. The 10 mg dose is not an WARNINGS AND PRECAUTIONSapproved dose. A total of 1232 patients (including approximately 40% elderly patientsCNS-Depressant Effects and Daytime Impairment[ 65 years old]), received QUVIVIQ 50 mg (N = 308); 25 mg (N = 618); or 10 mg (an QUVIVIQ is a central nervous system (CNS) depressant that can impair daytimeunapproved dose) (N = 306). A total of 576 patients were treated with QUVIVIQ for at wakefulness even when used as prescribed. CNS-depressant effects may persist in someleast 6 months and 331 for at least 12 months. patients for up to several days after discontinuing QUVIVIQ. Prescribers should adviseMost Common Adverse Reactions patients about the potential for next-day somnolence.The most common reported adverse reaction (in at least 5% of patients and greater than Driving ability was impaired in some subjects taking QUVIVIQ 50 mg [see Clinical Studiesplacebo) during double-blind treatment in Study 1 was headache. in the full prescribing information]. The risk of daytime impairment is increased if QUVIVIQTable 1 shows adverse reactions that occurred in at least 2% of patients treated with is taken with less than a full night of sleep remaining or if a higher than recommendedQUVIVIQ and more frequently than in patients who received placebo in Study 1. dose is taken [see Dosage and Administration in the full prescribing information]. IfTable 1Adverse Reactions Reported in2% of QUVIVIQ-treated Patients andQUVIVIQ is taken in these circumstances, caution patients against driving and otherGreater than in Placebo-treated Patients in a 3-Month Placebo-Controlled activities requiring complete mental alertness.Study (Study 1) Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclicQUVIVIQQUVIVIQPlacebo antidepressants, alcohol) increases the risk of CNS depression, which can cause daytime25 mg50 mgimpairment. Dosage adjustments of QUVIVIQ and of concomitant CNS depressants may(N=310)(N=308)(N=309) 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 QUVIVIQNervous System Disorderswith alcohol resulted in additive effects on psychomotor performance [see DrugHeadache* 6 7 5Interactions].Somnolence or fatigue* 6 5 4Because QUVIVIQ can cause drowsiness, patients, particularly the elderly, are at a higherDizziness* 2 3 2risk of falls.Gastro-intestinal disordersWorsening of Depression/Suicidal IdeationNausea* 0 3 2Patients with psychiatric disorders, including insomnia, are at increased risk of suicide. In primarily depressed patients treated with hypnotics, worsening of depression and suicidal*The following terms were combined: thoughts and actions (including completed suicides) have been reported. As with otherHeadache includes: headache, tension headache, migraine, migraine with aura, head hypnotics, QUVIVIQ should be administered with caution in patients exhibiting symptomsdiscomfortof depression. Monitoring of suicide risk 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, labyrinthitisSymptomsNausea includes: nausea, vomiting, procedural nauseaSleep paralysis, an inability to move or speak for up to several minutes during sleep- Other Adverse Reactions Observed During Clinical Trials (Study 1 and Study 2) wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid andOther adverse reactions of 2% frequency but greater than placebo are shown below. disturbing perceptions, can occur with the use of QUVIVIQ [see Adverse Reactions].The following do not include adverse reactions 1) for which a drug cause was remote,Prescribers should explain the nature of these events to patients when prescribing2) that were so general as to be uninformative, or 3) that were not considered to have QUVIVIQ.clinically significant implications. Symptoms similar to mild cataplexy have been reported with orexin receptor antagonists. Sleep paralysis was reported in 0.5% and 0.3% of patients receiving QUVIVIQ 25 mg Such symptoms can include periods of leg weakness lasting from seconds to a fewand 50 mg, respectively, compared to no reports for placebo. minutes, can occur either at night or during the day, and may not be associated with an Hypnagogic and hypnopompic hallucinations were reported in 0.6% of patients identified triggering event (e.g., laughter or surprise)receiving QUVIVIQ 25 mg compared to no cases with QUVIVIQ 50 mg or placebo. Complex Sleep BehaviorsDRUG INTERACTIONS Complex sleep behaviors, including sleepwalking, sleep-driving, and engaging in otherDrugs Having Clinically Important Interactions with QUVIVIQactivities while not fully awake (e.g., preparing and eating food, making phone calls,Table 2Clinically Important Drug Interactions with QUVIVIQ 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-nave as wellStrong or Moderate CYP3A4 Inhibitorsas in hypnotic-experienced persons. Patients usually do not remember these events.ClinicalConcomitant use with a strong or moderate CYP3A4 inhibitor Complex sleep behaviors may occur following the first or any subsequent use ofImplications: increases exposure to daridorexant [see Clinical Pharmacology in the hypnotics, such as QUVIVIQ, with or without the concomitant use of alcohol and otherfull prescribing information], which may increase the risk of QUVIVIQ CNS depressants [see Drug Interactions]. Discontinue QUVIVIQ immediately if a patientadverse reactions.experiences a complex sleep behavior.Prevention orThe recommended dose of QUVIVIQ is 25 mg when used with a Patients with Compromised Respiratory FunctionManagement: moderate CYP3A4 inhibitor [see Dosage and Administration in the full The effects of QUVIVIQ on respiratory function should be considered if prescribed toprescribing information].patients with compromised respiratory function. QUVIVIQ has not been studied in patientsConcomitant use of QUVIVIQ with a strong inhibitor of CYP3A4 is not with moderate OSA requiring CPAP or severe OSA. QUVIVIQ has not been studied inrecommended [see Dosage and Administration in the full prescribing patients with severe COPD [see Use in Specific Populations].information].Need to Evaluate for Co-morbid DiagnosesStrong and Moderate CYP3A4 InducersBecause sleep disturbances may be the presenting manifestation of a medical and/or psychiatric disorder, treatment of insomnia should be initiated only after careful evaluationClinicalConcomitant use with a strong or moderate CYP3A4 inducer of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicateImplications: decreases exposure to daridorexant [see Clinical Pharmacology in the the presence of a primary psychiatric and/or medical illness that should be evaluated.full prescribing information], which may reduce the efficacy of Worsening of insomnia or the emergence of new cognitive or behavioral abnormalitiesQUVIVIQ.may be the result of an unrecognized underlying psychiatric or medical disorder and canPrevention orConcomitant use of QUVIVIQ with a strong or moderate inducer of emerge during the course of treatment with sleep-promoting drugs such as QUVIVIQ.Management: CYP3A4 is not recommended [see Dosage and Administration in the ADVERSE REACTIONSfull prescribing information].The following are discussed in detail in other sections of the labeling:Alcohol and Other CNS Depressants CNS-Depressant Effects and Daytime Impairment [see Warnings and Precautions]ClinicalConcomitant use of alcohol or other CNS depressants with QUVIVIQWorsening of Depression/Suicidal Ideation [see Warnings and Precautions]Implications: may lead to additive impairment of psychomotor performance andSleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-likerisk of CNS depression [see Clinical Pharmacology in the full Symptoms [see Warnings and Precautions]prescribing information]. Complex Sleep Behaviors [see Warnings and Precautions](continued) Patients with Compromised Respiratory Function [see Warnings and Precautions]'