QUVIVIQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for QUVIVIQ (QUVIVIQ).
Dual orexin receptor antagonist (DORA) that inhibits orexin-mediated wakefulness by blocking orexin receptors OX1R and OX2R in the hypothalamus.
| Metabolism | Primarily metabolized by CYP3A4; also involves CYP2C19 to a minor extent. |
| Excretion | Renal: ~29% as unchanged drug; fecal: ~50% (parent and metabolites); biliary: minor. Total recovery ~90% in urine and feces |
| Half-life | Terminal half-life ~50 hours (range 40-60 h) for 50 mg dose; supports once-daily dosing. Steady state reached in ~2 weeks |
| Protein binding | ~94% bound, primarily to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | ~5 L/kg (range 4-6 L/kg); indicates extensive extravascular distribution into tissues, including brain |
| Bioavailability | Oral: absolute bioavailability ~32% (range 25-40%) due to first-pass metabolism; food increases Cmax by 47% and AUC by 30% |
| Onset of Action | Oral: median time to sleep onset ~30 minutes (range 20-60 min) based on polysomnography; clinical onset within first night |
| Duration of Action | Sustained sleep maintenance; drug concentrations remain above therapeutic threshold for ~8-10 hours; clinical effect lasts through the night. No residual morning impairment in most patients |
25 mg orally once daily, immediately before bedtime, with at least 7 hours remaining before planned awakening.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). For severe renal impairment (eGFR 15-29 mL/min), dosage recommendation is 17.5 mg orally once daily. Not recommended in end-stage renal disease (eGFR <15 mL/min). |
| Liver impairment | No dosage adjustment required for mild hepatic impairment (Child-Pugh A). For moderate hepatic impairment (Child-Pugh B), maximum dose is 17.5 mg orally once daily. Not recommended in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy have not been established in pediatric patients (age <18 years). No recommended dose. |
| Geriatric use | Maximum dose of 17.5 mg orally once daily for patients aged 65 years and older. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for QUVIVIQ (QUVIVIQ).
| Breastfeeding | It is unknown if daridorexant is excreted in human milk. The M/P ratio has not been determined. Due to the potential for somnolence and respiratory depression in breastfed infants, breastfeeding is not recommended during treatment. |
| Teratogenic Risk | QUVIVIQ (daridorexant) has no adequate and well-controlled studies in pregnant women. In animal reproduction studies, no teratogenic effects were observed at exposures up to 28 times the maximum recommended human dose. However, potential fetal risks include somnolence and respiratory depression in neonates if exposed in the third trimester. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to daridorexant or any excipients","Concomitant use with strong CYP3A4 inhibitors","Narcolepsy"]
| Precautions | ["CNS depressant effects: may impair daytime wakefulness","Risk of next-day impairment, including driving impairment","Worsening of depression or suicidal ideation","Sleep paralysis, hypnagogic/hypnopompic hallucinations, and complex sleep behaviors","Use with caution in patients with compromised respiratory function","Not recommended in patients with severe hepatic impairment"] |
Loading safety data…
| Fetal Monitoring | Monitor pregnant women for excessive sedation and respiratory depression. If used near term, monitor neonates for signs of somnolence, respiratory depression, and withdrawal. |
| Fertility Effects | In animal studies, daridorexant did not impair fertility in males or females at exposures up to 28 times the MRHD. No human data on fertility effects are available. |