b'QUVIVIQ (daridorexant) tablets, for oral use, CIV QUVIVIQ (daridorexant) tablets, for oral use, CIVTable 2Effects of Other Drugs on QUVIVIQPatients with Compromised Respiratory FunctionAlcohol and Other CNS Depressants Obstructive sleep apneaClinicalConcomitant use of alcohol or other CNS depressants withThe respiratory depressant effect of QUVIVIQ was evaluated after one night and Implications: QUVIVIQ may lead to additive impairment of psychomotorafter five consecutive nights of treatment in a randomized, placebo-controlled, performance and risk of CNS depression. two-period crossover study in 25 patients with mild to moderate OSA (apnea-hypopnea index [AHI] 5 to 30 events per hour) not requiring CPAP. Following Prevention orAvoid alcohol consumption with QUVIVIQ [see Warnings andonce-daily dosing of 50 mg, the mean treatment difference (daridorexantManagement: Precautions]. placebo) on Day 5 for AHI was 0.74 (90% CI, -1.43 to 2.92).Use with caution in patients receiving CNS depressants. ConsiderDue to study limitations, including the short duration of the study, clinically dose adjustment of QUVIVIQ and/or the CNS depressant(s) ifmeaningful respiratory effects of QUVIVIQ in OSA cannot be excluded, including used concomitantly [see Warnings and Precautions]. for long-term treatment.Effects of QUVIVIQ on Other Drugs QUVIVIQ has not been studied in patients with severe OSA (AHI30) or those Table 3 describes clinically significant drug interactions where the concomitantrequiring CPAP [see Warnings and Precautions].use of QUVIVIQ affects other drugs. Chronic obstructive pulmonary diseaseTable 3Effects of QUVIVIQ on Other Drugs The respiratory depressant effect of QUVIVIQ was evaluated after one night and after five consecutive nights of treatment in a randomized, placebo-controlled, CYP3A4 Substrates two-period crossover study in 25 patients with moderate COPD (FEV 1 /FVC ratio ClinicalConcomitant use of QUVIVIQ with CYP3A4 substrates increases 70% and 40%FEV 1 80% of predicted). Following once-daily dosing of 50 mg, Implications: the exposure to CYP3A4 substrate. the mean SpO 2treatment difference (daridorexantplacebo) on Day 5 was 0.18%(90% CI, -0.21 to 0.57).Prevention orUse with caution in patients receiving CYP3A4 substrates withQUVIVIQ has not been studied in patients with severe COPD (FEV 1 40% of Management: narrow therapeutic index. predicted).P-gp Substrates Clinically meaningful respiratory effects of QUVIVIQ in patients with compromised ClinicalConcomitant use of QUVIVIQ with P-gp substrates increasesrespiratory function cannot be excluded [see Warnings and Precautions].Implications: the exposure to P-gp substrate. DRUG ABUSE AND DEPENDENCEPrevention orUse with caution in patients receiving P-gp substrates with aControlled SubstanceManagement: narrow therapeutic index. QUVIVIQ contains daridorexant, a Schedule IV controlled substance.USE IN SPECIFIC POPULATIONS AbusePregnancy Drug abuse is the intentional, non-therapeutic use of a drug, even once, for Pregnancy Exposure Registry its desirable psychological or physiological effects. The abuse potential of There will be a pregnancy exposure registry that monitors pregnancy outcomes daridorexant was evaluated in preclinical models, recreational sedative drug in women exposed to QUVIVIQ during pregnancy. Pregnant women exposed to users, and insomnia subjects. QUVIVIQ and healthcare providers are encouraged to call Idorsia Pharmaceuticals LtdIn a human abuse potential study conducted in 63 recreational sedative drug at 1-833-400-9611. users, the effect of single-dose administration of QUVIVIQ [50 mg, 100 mg Risk Summary (two times the maximum recommended dose), and 150 mg (three times the maximum recommended dose)], zolpidem (30 mg), suvorexant (150 mg), and There are no available data on QUVIVIQ use in pregnant women to evaluateplacebo on subjective rating of drug liking was evaluated. At the dose of 50 mg, for drug-associated risks of major birth defects, miscarriage, or other adverseQUVIVIQ showed significantly lower drug liking ratings than zolpidem (30 mg) maternal or fetal outcomes. In animal reproduction studies, oral administrationand suvorexant (150 mg), but significantly higher than placebo. At doses ofof daridorexant to pregnant rats and rabbits during the period of organogenesis100 mg (two times the maximum recommended dose) and 150 mg (three times did not cause fetal toxicity or malformation at doses up to 8 and 10 times thethe maximum recommended dose), QUVIVIQ showed similar drug liking maximum recommended human dose (MRHD) of 50 mg, respectively, based onratings to zolpidem (30 mg) and suvorexant (150 mg).AUC. Oral administration of daridorexant to pregnant and lactating rats did notIn placebo-controlled Phase 3 clinical studies in which 1232 subjects with cause any maternal or developmental toxicity at doses up to 9 times the MRHD,insomnia were treated with QUVIVIQ for up to 12 months, there were no reports based on AUC. indicative of abuse liability. Because individuals with a history of abuse of or The estimated background risk of major birth defects and miscarriage for theaddiction to alcohol or other drugs may be at increased risk for abuse of or indicated population is unknown. All pregnancies have a background risk ofaddiction to QUVIVIQ, follow such patients carefully.birth defect, loss, or other adverse outcomes. In the U.S. general population, theDependenceestimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.Physical dependence is a state that develops as a result of physiological adaptation Lactationin response to repeated drug use, manifested by withdrawal signs and symptomsRisk Summary upon abrupt treatment discontinuation or a significant dose reduction of a drug. There are no data on the presence of daridorexant in human milk, the effectsIn animal studies and clinical trials evaluating physical dependence, chronic on the breastfed infant, or the effects on milk production. Daridorexant and itsadministration of daridorexant did not produce withdrawal signs or symptoms metabolites were present in the milk of lactating rats. When a drug is present inupon drug discontinuation. This suggests that daridorexant does not produce animal milk, it is likely that the drug will be present in human milk.physical dependence.Infants exposed to QUVIVIQ through breastmilk should be monitored for excessiveOVERDOSAGEsedation. The developmental and health benefits of breastfeeding should beThere is limited clinical experience with QUVIVIQ overdose. In clinical pharmacology considered along with the mothers clinical need for QUVIVIQ and any potentialstudies, healthy subjects were administered single doses of up to 200 mg (4 timesadverse effects on the breastfed infant from QUVIVIQ or from the underlyingthe maximum recommended dose) of QUVIVIQ. The following adverse reactions maternal condition. were observed: somnolence, muscle weakness, cataplexy-like symptoms, sleep paralysis, disturbance in attention, fatigue, headache, and constipation. Pediatric Use There is no specific antidote to an overdosage of QUVIVIQ. In the event of anThe safety and effectiveness of QUVIVIQ have not been established in pediatricoverdose, general symptomatic and supportive medical care, along with immediate patients. gastric lavage where appropriate, should be provided and patients should be Geriatric Use carefully monitored. Dialysis is unlikely to be effective as daridorexant is highly No dose adjustment is required in patients over the age of 65 years. protein bound. Consult a Certified Poison Control Center for the most up to date Of the total number of subjects in the clinical studies of QUVIVIQ with insomniainformation on the management of overdosage (1-800-222-1222 or(N = 1854), approximately 39% (N = 727) were65 years and 5.9% (N = 110)www.poison.org). were75 years. The likelihood of somnolence and fatigue increased with patient age.Distributed by:Because QUVIVIQ can increase somnolence and drowsiness, patients, particularlyIdorsia Pharmaceuticals US Inc.the elderly, are at higher risk of falls [see Warnings and Precautions].One Radnor Corporate Center, Suite 101100 Matsonford RdHepatic Impairment Radnor, PA 19087QUVIVIQ has not been studied in patients with severe hepatic impairment (Child- IDRS10162023Pugh score10). Use in this population is not recommended. Patent: www.idorsia.com/patentsReduce the dose of QUVIVIQ in patients with moderate hepatic impairment (Child-Pugh score 79). Moderate hepatic impairment may increase daridorexantUS-DA-0028310/2023systemic exposure to a clinically relevant extent, which may increase the frequency or severity of adverse reactions.'