Daridorexant (Quviviq) Dosing and Treatment Approach
The recommended starting dose of daridorexant is 50 mg taken orally once nightly within 30 minutes of bedtime, with at least 7 hours remaining before planned awakening, as this dose provides maximal efficacy for both sleep onset and maintenance without increased adverse events compared to lower doses. 1, 2
Standard Dosing Regimen
50 mg is the preferred dose for most patients with insomnia disorder, providing the greatest opportunity for efficacy across all sleep parameters (wake after sleep onset, latency to persistent sleep, and total sleep time) 1, 2
25 mg is an alternative lower dose that can be used, though it demonstrates less robust efficacy, particularly for daytime functioning improvements 1, 2
The medication should be taken within 30 minutes of going to bed with at least 7 hours remaining before the planned wake time 1
Avoid taking with or soon after meals, as food delays time to sleep onset 1
Dose Modifications for Drug Interactions
Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) entirely 1
Reduce to 25 mg maximum when using moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, erythromycin) 1
Avoid concomitant use with strong or moderate CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin), as they significantly reduce daridorexant efficacy 1
Dose Modifications for Hepatic Impairment
Maximum 25 mg dose for patients with moderate hepatic impairment (Child-Pugh score 7-9) 1
Not recommended in patients with severe hepatic impairment (Child-Pugh score ≥10) 1
No dose adjustment needed for renal impairment 1
Efficacy Profile
The 50 mg dose demonstrates superior efficacy compared to placebo and lower doses:
- Wake after sleep onset: Reduced by approximately 13-20 minutes compared to placebo 3, 4
- Latency to persistent sleep: Reduced by approximately 7-15 minutes compared to placebo 3, 4
- Subjective total sleep time: Increased by approximately 15-60 minutes compared to placebo 3, 4
- Daytime functioning: Progressively improved from week 1 onwards, measured by IDSIQ scores 4
Importantly, dose-response analyses demonstrate linear efficacy relationships across the dose range without reaching a plateau, supporting 50 mg as the optimal dose 2
Special Populations
Older Adults (≥65 years)
Use the full 50 mg dose in older adults without dose reduction, as efficacy is comparable to younger adults and older patients particularly require this dose to improve daytime functioning 4
Older adults show no increased risk of adverse events, falls, or next-morning residual effects at the 50 mg dose compared to younger adults 4
Baseline wake after sleep onset is typically higher in older adults (110 vs 92 minutes), making the full dose especially important 4
Patients with Comorbid Mild Obstructive Sleep Apnea
Daridorexant 50 mg is safe and effective in patients with untreated mild OSA (apnea-hypopnea index 5-<15 events/hour) and comorbid insomnia 5
The 25 mg dose was not consistently superior to placebo in this population, further supporting 50 mg as the preferred dose 5
Safety Profile
No dose-dependent increase in adverse events across the dose range, including somnolence and fatigue 2, 6
The most common adverse events are somnolence and fatigue, occurring at slightly higher rates than placebo but remaining low overall 6
No cases of complex sleep behaviors, cataplexy, or narcolepsy reported in clinical trials 4
Morning sleepiness actually improved (not worsened) with daridorexant treatment in both age groups 4
Contraindications
Absolute contraindication in patients with narcolepsy 1
Contraindicated in patients with hypersensitivity to daridorexant or any components, including those with prior angioedema 1
Important Warnings
CNS depressant effects can impair daytime wakefulness and driving ability, particularly with the 50 mg dose 1
Patients should be counseled to avoid driving or operating machinery if they experience daytime somnolence 1
Avoid alcohol and other CNS depressants during treatment, as additive effects may occur 1
Risk of impairment increases if taken with less than 7 hours of sleep time remaining or at higher than recommended doses 1
Common Pitfalls to Avoid
Do not start with 25 mg routinely in an attempt to "start low and go slow"—the 50 mg dose provides maximal efficacy without increased adverse events and should be the default starting dose for most patients 2
Do not reduce the dose in older adults based solely on age, as they tolerate and benefit from the full 50 mg dose 4
Do not continue 25 mg if inadequate response—uptitrate to 50 mg rather than switching to a different medication 2
Do not overlook drug interactions with CYP3A4 inhibitors/inducers, which significantly affect daridorexant levels 1