b'QUVIVIQ (daridorexant) tablets, for oral use, CIVQUVIVIQ (daridorexant) tablets, for oral use, CIV Table 2Clinically Important Drug Interactions with QUVIVIQ Moderate hepatic impairment may increase daridorexant systemic exposure to a Alcohol and Other CNS Depressants clinically relevant extent [see Clinical Pharmacology in the full prescribing information], Prevention orAvoid alcohol consumption with QUVIVIQ [see Warnings andwhich may increase the frequency or severity of adverse reactions. Management: Precautions]. Patients with Compromised Respiratory FunctionUse with caution in patients receiving CNS depressants. ConsiderObstructive sleep apnea dose adjustment of QUVIVIQ and/or the CNS depressant(s) if usedThe respiratory depressant effect of QUVIVIQ was evaluated after one night and afterconcomitantly [see Warnings and Precautions]. five consecutive nights of treatment in a randomized, placebo-controlled, two-period crossover study in 25 patients with mild to moderate OSA (apnea-hypopnea index [AHI] USE IN SPECIFIC POPULATIONS5 to 30 events per hour) not requiring CPAP. Following once-daily dosing of 50 mg, the Pregnancymean treatment difference (daridorexantplacebo) on Day 5 for AHI was 0.74 (90% CI, Pregnancy Exposure Registry-1.43 to 2.92). There will be a pregnancy exposure registry that monitors pregnancy outcomes inDue to study limitations, including the short duration of the study, clinically meaningful women exposed to QUVIVIQ during pregnancy. Pregnant women exposed to QUVIVIQrespiratory effects of QUVIVIQ in OSA cannot be excluded, including for long-term and healthcare providers are encouraged to call Idorsia Pharmaceuticals Ltd at treatment. 1-833-400-9611.QUVIVIQ has not been studied in patients with severe OSA (AHI30) or those requiring Risk SummaryCPAP [see Warnings and Precautions]. There are no available data on QUVIVIQ use in pregnant women to evaluate for drug- Chronic obstructive pulmonary disease associated risks of major birth defects, miscarriage, or other adverse maternal or fetalThe respiratory depressant effect of QUVIVIQ was evaluated after one night and afteroutcomes. In animal reproduction studies, oral administration of daridorexant tofive consecutive nights of treatment in a randomized, placebo-controlled, two-period pregnant rats and rabbits during the period of organogenesis did not cause fetal toxicitycrossover study in 25 patients with moderate COPD (FEV 1 /FVC ratio70% and 40%or malformation at doses up to 8 and 10 times the maximum recommended human FEV 1 80% of predicted). Following once-daily dosing of 50 mg, the mean SpO 2dose (MRHD) of 50 mg, respectively, based on AUC. Oral administration of daridorexanttreatment difference (daridorexantplacebo) on Day 5 was 0.18% (90% CI, -0.21 to 0.57). to pregnant and lactating rats did not cause any maternal or developmental toxicity atQUVIVIQ has not been studied in patients with severe COPD (FEV 1 40% of predicted). doses up to 9 times the MRHD, based on AUC (see Data). The estimated background risk of major birth defects and miscarriage for the indicatedClinically meaningful respiratory effects of QUVIVIQ in patients with compromised population is unknown. All pregnancies have a background risk of birth defect, loss, orrespiratory function cannot be excluded [see Warnings and Precautions]. other adverse outcomes. In the U.S. general population, the estimated background riskDRUG ABUSE AND DEPENDENCE of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4%Controlled Substance and 15% to 20%, respectively.QUVIVIQ contains daridorexant, a Schedule IV controlled substance. DataAbuse Animal DataDrug abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. The abuse potential of daridorexant was evaluated Daridorexant was administered orally to pregnant rats during the period of organogenesisin preclinical models, recreational sedative drug users, and insomnia subjects. at doses of 30, 100, and 300 mg/kg/day, which are approximately 1, 3, and 8 times theIn a human abuse potential study conducted in 63 recreational sedative drug users,MRHD of 50 mg, respectively, based on AUC. Daridorexant did not cause any maternal orthe effect of single-dose administration of QUVIVIQ [50 mg, 100 mg (two times the embryofetal toxicities or fetal malformation at doses up to 300 mg/kg/day. The NOAELmaximum recommended dose), and 150 mg (three times the maximum recommended for maternal and fetal toxicity is 300 mg/kg/day, which is approximately 8 times the MRHDdose)], zolpidem (30 mg), suvorexant (150 mg), and placebo on subjective rating of of 50 mg, based on AUC.drug liking was evaluated. At the dose of 50 mg, QUVIVIQ showed significantly lower Daridorexant was administered orally to pregnant rabbits during the period of organogenesisdrug liking ratings than zolpidem (30 mg) and suvorexant (150 mg), but significantly at doses of 30, 60, and 120 mg/kg/day, which are approximately 3, 4, and 10 times thehigher than placebo. At doses of 100 mg (two times the maximum recommended dose) MRHD of 50 mg, respectively, based on AUC. Daridorexant did not cause any fetal toxicityand 150 mg (three times the maximum recommended dose), QUVIVIQ showed similar or malformation at doses up to 120 mg/kg/day. Daridorexant caused maternal toxicitiesdrug liking ratings to zolpidem (30 mg) and suvorexant (150 mg). of decreased weight gain and food consumption at the dose of 120 mg/kg/day. TheIn placebo-controlled Phase 3 clinical studies in which 1232 subjects with insomnia were NOAELs for maternal and fetal toxicity are 60 and 120 mg/kg/day, respectively, which treated with QUVIVIQ for up to 12 months, there were no reports indicative of abuse are approximately 4 and 10 times the MRHD of 50 mg, respectively, based on AUC.liability. Because individuals with a history of abuse of or addiction to alcohol or other Daridorexant was administered orally to pregnant rats during gestation and lactation atdrugs may be at increased risk for abuse of or addiction to QUVIVIQ, follow such patients doses of 50, 100, and 300 mg/kg/day, which are approximately 1, 3, and 9 times thecarefully. MRHD of 50 mg, respectively, based on AUC. Daridorexant did not cause any maternalDependence or developmental toxicities at doses up to 300 mg/kg/day. The NOAEL for maternal andPhysical dependence is a state that develops as a result of physiological adaptation in developmental toxicity is 300 mg/kg/day, which is approximately 9 times the MRHD ofresponse to repeated drug use, manifested by withdrawal signs and symptoms upon 50 mg, based on AUC.abrupt treatment discontinuation or a significant dose reduction of a drug. LactationIn animal studies and clinical trials evaluating physical dependence, chronic administration Risk Summaryof daridorexant did not produce withdrawal signs or symptoms upon drug discontinuation. There are no data on the presence of daridorexant in human milk, the effects on theThis suggests that daridorexant does not produce physical dependence. breastfed infant, or the effects on milk production. Daridorexant and its metabolites wereOVERDOSAGE present in the milk of lactating rats. When a drug is present in animal milk, it is likelyThere is limited clinical experience with QUVIVIQ overdose. In clinical pharmacology that the drug will be present in human milk.studies, healthy subjects were administered single doses of up to 200 mg (4 times the Infants exposed to QUVIVIQ through breastmilk should be monitored for excessivemaximum recommended dose) of QUVIVIQ. The following adverse reactions were sedation. The developmental and health benefits of breastfeeding should be consideredobserved: somnolence, muscle weakness, cataplexy-like symptoms, sleep paralysis, along with the mothers clinical need for QUVIVIQ and any potential adverse effects ondisturbance in attention, fatigue, headache, and constipation. the breastfed infant from QUVIVIQ or from the underlying maternal condition.There is no specific antidote to an overdosage of QUVIVIQ. In the event of an overdose, Pediatric Usegeneral symptomatic and supportive medical care, along with immediate gastric lavage The safety and effectiveness of QUVIVIQ have not been established in pediatric patients.where appropriate, should be provided and patients should be carefully monitored. Geriatric UseDialysis is unlikely to be effective as daridorexant is highly protein bound. Consult a No dose adjustment is required in patients over the age of 65 years.Certified Poison Control Center for the most up to date information on the management Of the total number of subjects in the clinical studies of QUVIVIQ with insomnia (N = 1854),of overdosage (1-800-222-1222 or www.poison.org). approximately 39% (N = 727) were65 years and 5.9% (N = 110) were75 years. The likelihood of somnolence and fatigue increased with patient age.Distributed by: Because QUVIVIQ can increase somnolence and drowsiness, patients, particularly theIdorsia Pharmaceuticals US Inc. elderly, are at higher risk of falls [see Warnings and Precautions].One Radnor Corporate Center, Suite 101Hepatic Impairment100 Matsonford Rd QUVIVIQ has not been studied in patients with severe hepatic impairment (Child-PughRadnor, PA 19087score10). Use in this population is not recommended [see Clinical Pharmacology inIDRS01192022 the full prescribing information].Patent: www.idorsia.com/patents Reduce the dose of QUVIVIQ in patients with moderate hepatic impairment (Child-PughUS-DA-00283score 79) [see Dosage and Administration in the full prescribing information].'