Daridorexant
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Insomnia characterized by difficulties with sleep onset and/or sleep maintenance | Adults | Monotherapy | FDA Approved |
Daridorexant is the third dual orexin receptor antagonist (DORA) approved by the FDA, following suvorexant (2014) and lemborexant (2019). It was approved on January 7, 2022, and became commercially available in the US in May 2022 after DEA Schedule IV scheduling. Among the DORAs, daridorexant has the shortest effective half-life (~8 hours), a property selected during development to minimize next-day residual effects. The pivotal Phase 3 program (Studies 1 and 2, published as Mignot et al. Lancet Neurology 2022) was the first insomnia trial program to formally demonstrate that an insomnia drug improves patient-reported daytime functioning using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), in addition to objective polysomnographic improvements in latency to persistent sleep and wake after sleep onset.
Cognitive behavioral therapy for insomnia (CBT-I) remains first-line in both AASM and ACP guidance, with pharmacotherapy reserved for patients in whom CBT-I is unavailable, has failed, or is needed as a temporary adjunct. The 2017 AASM clinical practice guideline pre-dates daridorexant approval and therefore does not contain a specific recommendation for it.
Insomnia in dementia populations — Unlike suvorexant (whose label was updated in 2020 to include findings from a phase 3 Alzheimer disease trial) and lemborexant (which has phase 2 data in irregular sleep–wake rhythm disorder with AD), daridorexant has not been studied in dedicated dementia-population trials. Use in mild cognitive impairment or early dementia is therefore extrapolation from the general insomnia population. Evidence quality: very low (extrapolation only).
Delirium prevention in hospitalized patients — Limited case series and small observational studies; the published evidence base is far less mature than for suvorexant or ramelteon. Evidence quality: very low.
Shift-work-related sleep disturbance and circadian rhythm disorders — Mechanistically plausible but not formally studied in registered trials. Evidence quality: very low.
Dosing
The recommended dosage range is 25 mg to 50 mg taken orally once per night within 30 minutes of going to bed, with at least 7 hours remaining before planned awakening. Unlike suvorexant and lemborexant, the FDA label provides a flexible dose range rather than a strict starting-dose-then-titrate algorithm; many prescribers begin at 25 mg in older or sensitive patients and 50 mg when substantial sleep maintenance impairment is the dominant complaint. Concomitant CYP3A4 inhibitors and hepatic impairment dictate specific dose ceilings, and concomitant strong or moderate CYP3A4 inducers must be avoided altogether.
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Adult insomnia (sleep onset and/or maintenance) — primary indication | 25–50 mg PO | 25–50 mg nightly | 50 mg/day | Take within 30 min of bed; ≥7 h before planned awakening Choose dose based on relative weight of sleep onset vs maintenance complaint and patient sensitivity |
| Older adults (≥65 years) | 25 mg PO | 25–50 mg nightly | 50 mg/day | No formal dose adjustment per label Likelihood of somnolence and fatigue increases with age; falls risk should be considered before escalation to 50 mg |
| Mild hepatic impairment (Child-Pugh A) | 25–50 mg PO | 25–50 mg nightly | 50 mg/day | No dose adjustment required |
| Moderate hepatic impairment (Child-Pugh B, score 7–9) | 25 mg PO | 25 mg nightly | 25 mg/day | Maximum 25 mg AUC and Cmax increased to a clinically relevant extent |
| Severe hepatic impairment (Child-Pugh C, score ≥10) | Not recommended | — | — | Not studied; avoid use |
| Renal impairment (mild, moderate, severe; not on dialysis) | 25–50 mg PO | 25–50 mg nightly | 50 mg/day | No dose adjustment required (CrCl <30 mL/min not on dialysis was studied without clinically significant PK change) |
| Concomitant moderate CYP3A4 inhibitor (e.g., diltiazem, verapamil, fluconazole, erythromycin, ciprofloxacin) | 25 mg PO | 25 mg nightly | 25 mg/day | Maximum 25 mg Diltiazem 240 mg increases daridorexant AUC ~2.4-fold |
| Concomitant strong CYP3A4 inhibitor (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir, posaconazole, nefazodone) | Avoid | Use alternative hypnotic Itraconazole predicted to increase daridorexant AUC by >400% (PBPK modeling) | ||
| Concomitant strong or moderate CYP3A4 inducer (e.g., rifampin, carbamazepine, phenytoin, St. John’s wort, efavirenz, modafinil) | Avoid | Choose a non-CYP3A-dependent hypnotic Efavirenz reduces daridorexant AUC to ~0.4× (60% reduction); rifampin predicted >50% reduction | ||
| Pediatric (<18 years) | Not established | — | — | Safety and effectiveness not established |
Daridorexant’s effective half-life of approximately 8 hours and absence of accumulation with chronic dosing distinguish it from the other DORAs (suvorexant ~12 h; lemborexant 17–19 h). The 7-hour rule still applies — the FDA label is explicit that daridorexant should not be administered unless ≥7 hours remain before required awakening — but the shorter half-life is the design rationale behind its labeled improvement in daytime functioning, the first such demonstration for any insomnia drug. CNS depressant effects can still persist for several days after discontinuation in some patients, particularly older adults.
If insomnia fails to remit after 7–10 days of treatment, the FDA label advises re-evaluation for an underlying psychiatric or medical disorder rather than continued empiric treatment.
Pharmacology of Daridorexant
Mechanism of Action
Daridorexant is a competitive antagonist at the orexin OX1R and OX2R receptors with high in vitro potency (Ki = 0.47 nM and 0.93 nM, respectively). The orexin (hypocretin) signaling system, originating in the lateral hypothalamus, drives wakefulness through projections to monoaminergic and cholinergic arousal nuclei; orexin A and orexin B are the principal endogenous neuropeptides. By blocking their binding at OX1R and OX2R, daridorexant suppresses wake drive rather than augmenting sleep drive — a mechanism that does not reproduce the GABAergic enhancement of benzodiazepine receptor agonists. The drug was selected from a pool of candidates specifically for an expected duration of effect of approximately 8 hours at therapeutic doses, with the aim of providing a full night of sleep coverage while minimising next-day residual sedation. As with the other DORAs, narcolepsy is the only labeled contraindication on mechanistic grounds, since the underlying pathology of human narcolepsy with cataplexy is loss of orexin signaling.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Tmax 1–2 h; absolute oral bioavailability ~62%; dose-proportional from 25 to 50 mg; high-fat meal delays Tmax by ~1.3 h and decreases Cmax by ~16% but does not affect AUC | Take on a relatively empty stomach for fastest sleep-onset effect; the AUC-preserving food effect means total exposure is unchanged |
| Distribution | Vd ~31 L; plasma protein binding 99.7%; blood-to-plasma ratio 0.64 | Compact distribution volume; high protein binding means hemodialysis is not effective in overdose |
| Metabolism | Hepatic; CYP3A4 accounts for ~89% of metabolic clearance; other CYPs each contribute <3% individually | CYP3A4 dominates the interaction profile — strong inhibitors must be avoided, moderate inhibitors require dose reduction to 25 mg, and strong or moderate inducers must be avoided |
| Elimination | Terminal t½ ~8 h; ~57% feces, ~28% urine (both primarily as metabolites); trace parent drug in feces and urine; no accumulation with multiple-dose administration | Shortest half-life among the marketed DORAs; absence of accumulation simplifies long-term use; clinically meaningful next-day exposure is lower than with suvorexant or lemborexant |
Side Effects
The pivotal program enrolled 1,854 adults with DSM-5 insomnia disorder across two 3-month placebo-controlled trials (Study 1, NCT03545191; Study 2, NCT03575104) and a 9-month extension (Study 3). A total of 1,232 patients received daridorexant in the safety population, with 576 treated for at least 6 months and 331 for at least 12 months. Approximately 40% of subjects were ≥65 years. The most common adverse reactions in the FDA Table 1 (≥2% on daridorexant and greater than placebo, Study 1) were headache and somnolence/fatigue, both at single-digit incidence rates and only modestly above placebo. Driving impairment was statistically significant compared to placebo after the first dose at 50 mg in healthy volunteers but was not statistically significant after 4 consecutive nights, although individual sensitivity was variable. The narcolepsy-spectrum events characteristic of the DORA class (sleep paralysis, hypnagogic/hypnopompic hallucinations, cataplexy-like leg weakness) are uncommon at recommended doses.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| None reported at this frequency in pivotal trials | — | No adverse event reached ≥10% incidence on daridorexant 25 mg or 50 mg in pivotal placebo-controlled trials |
| Adverse Effect | Incidence (25 mg / 50 mg) | Clinical Note |
|---|---|---|
| Headache (incl. tension headache, migraine, head discomfort) | 6% / 7% | Placebo 5%; usually mild and self-limiting |
| Somnolence or fatigue (incl. sedation, hypersomnia, lethargy) | 6% / 5% | Placebo 4%; rate of somnolence/fatigue increases with patient age |
| Dizziness (incl. vertigo, labyrinthitis) | 2% / 3% | Placebo 2%; counsel older adults about overnight ambulation |
| Nausea (incl. vomiting, procedural nausea) | 0% / 3% | Placebo 2%; only at the 50 mg dose |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Daytime impairment / impaired driving | Statistically significant after first dose at 50 mg in driving-simulator study; not statistically significant after 4 nights | Morning after dose; may persist for several days after discontinuation in some patients | Counsel against next-day driving; reduce to 25 mg or discontinue if daytime somnolence develops |
| Complex sleep behaviors (sleep-walking, sleep-driving, preparing/eating food, phone calls, sex with amnesia) | Reported with hypnotics including DORAs | Any time during therapy, including first dose | Discontinue immediately if any episode occurs; risk increased by alcohol and other CNS depressants |
| Worsening depression and emergence of suicidal ideation | Reported with hypnotics, particularly in primarily depressed patients | Variable | Use with caution in patients with depression; prescribe smallest feasible quantity to limit overdose risk; immediately evaluate any new behavioral signs or suicidal ideation |
| Sleep paralysis | 0.5% (25 mg) and 0.3% (50 mg); placebo 0% | Sleep–wake transitions | Reassure if isolated and brief; consider dose reduction or discontinuation if recurrent or distressing |
| Hypnagogic / hypnopompic hallucinations | 0.6% (25 mg); not reported at 50 mg or with placebo | Falling asleep or waking | Counsel proactively about the nature of these events; consider dose reduction or discontinuation if recurrent |
| Cataplexy-like symptoms (transient leg weakness, day or night) | Reported with orexin receptor antagonists; not necessarily emotion-triggered | Variable | Consider dose reduction or discontinuation; assess fall risk in older adults |
| Hypersensitivity reactions (post-marketing) — angioedema, rash, urticaria; angioedema with pharyngeal involvement reported | Frequency not established (post-marketing) | Any time | Permanently discontinue; treat as standard angioedema/anaphylaxis. Hypersensitivity to daridorexant is now a labeled contraindication (added October 2023) |
| Respiratory depression in compromised patients | Studied in mild–severe OSA and moderate COPD; clinically meaningful effects cannot be excluded | Variable | Consider risks before prescribing in OSA, COPD, or with concomitant opioids. Not studied in mild or severe COPD |
| Abuse and dependence (Schedule IV) | At 50 mg, “drug liking” significantly lower than zolpidem 30 mg or suvorexant 150 mg in recreational users; at supratherapeutic 100–150 mg doses, similar to comparators | Variable | Screen substance-use history; monitor for misuse. No physical dependence in clinical trials |
The pivotal Phase 3 program was the first insomnia drug program to demonstrate a statistically significant improvement in patient-reported daytime functioning (Insomnia Daytime Symptoms and Impacts Questionnaire — IDSIQ — sleepiness domain) at the 50 mg dose, alongside the conventional sleep onset and maintenance endpoints. This is the principal clinical positioning argument for choosing daridorexant within the DORA class — the trade-off is brand-only pricing and the absence of a US generic.
Drug Interactions
Daridorexant is a CYP3A4 substrate, with ~89% of metabolic clearance attributable to that enzyme; CYP3A4 inhibitors and inducers therefore dominate the pharmacokinetic interaction profile. Daridorexant itself causes mild-to-moderate increases in exposure of CYP3A4 substrates and P-gp substrates with narrow therapeutic indices. Pharmacodynamic additivity with alcohol and other CNS depressants is the dominant non-PK concern. No clinically significant interaction has been observed with citalopram (an SSRI commonly co-prescribed with hypnotics).
Per the FDA label, dedicated PK/PD studies showed no clinically meaningful interactions when daridorexant 50 mg was co-administered with citalopram 20 mg, warfarin (CYP2C9 substrate), rosuvastatin (BCRP/OATP substrate), or famotidine (gastric pH modifier). Daridorexant does not appear to affect alcohol concentrations.
Monitoring
The FDA label does not specify routine laboratory monitoring for daridorexant. Clinical follow-up should focus on therapeutic response, daytime function (the principal clinical positioning advantage), dose-related neuropsychiatric and narcolepsy-spectrum events, falls in older adults, and — because daridorexant is a controlled substance — appropriate use and abuse-screening. The October 2023 contraindication for hypersensitivity adds a specific requirement to assess and document any prior reaction.
-
Sleep response
Reassess at 7–10 days, then periodically
Routine Track sleep latency, wake after sleep onset, total sleep time, and especially daytime function. Per the FDA label, failure of insomnia to remit after 7–10 days should prompt re-evaluation for an underlying psychiatric or medical disorder. -
Daytime function (IDSIQ-style review)
Each follow-up visit
Routine Specifically inquire about sleepiness, alertness, mood, and cognition during the day — daridorexant is the only insomnia drug with a labeled daytime functioning improvement, so the absence of expected benefit should prompt reconsideration of dose, diagnosis, or therapy. -
Daytime somnolence and driving
Each follow-up visit
Routine Inquire about morning grogginess and near-misses while driving. Driving impairment was statistically significant after the first 50 mg dose in healthy volunteers; counsel new starters specifically about the first few mornings. -
Falls and balance (older adults)
Each follow-up visit
Routine The likelihood of somnolence increases with age; assess gait stability and consider home safety review before increasing to 50 mg in patients ≥65. -
Mood and suicidal ideation
Each follow-up visit
Routine Worsening of depression and suicidal thoughts have been reported with hypnotics. PHQ-9 with item 9 review or C-SSRS is appropriate, particularly in patients with prior depression. Prescribe the smallest feasible quantity in at-risk patients. -
Complex sleep behaviors
Each follow-up visit
Routine Ask directly about sleep-walking, sleep-eating, sleep-driving, and unrecalled night-time activity. The label directs immediate discontinuation after any reported episode. -
Narcolepsy-spectrum events
Each follow-up visit
Routine Inquire about sleep paralysis, vivid hallucinations on falling asleep or waking, and transient leg weakness. Dose reduction or discontinuation if recurrent or distressing. -
Substance-use risk
Baseline; ongoing as indicated
Routine Schedule IV controlled substance. Screen for prior alcohol or sedative misuse before initiation; monitor for early refill requests or self-escalation. Daridorexant 50 mg had lower “drug liking” than zolpidem or supratherapeutic suvorexant in the abuse-liability study, but supratherapeutic doses (100–150 mg) had similar profiles. -
Hypersensitivity history
Baseline; with any new reaction
Trigger-based Hypersensitivity to daridorexant, including angioedema with pharyngeal involvement, has been reported post-marketing and is now a labeled contraindication (added October 2023). Document any prior reaction; permanently discontinue after any episode. -
Respiratory status
Baseline if compromised
Trigger-based Daridorexant has been studied in mild–severe OSA (without CPAP) and moderate COPD, but not in mild or severe COPD. Clinically meaningful respiratory effects cannot be excluded. -
Narrow-TI substrate effects
When co-administered
Trigger-based For patients on midazolam, dabigatran, or other narrow-TI CYP3A4 / P-gp substrates, monitor for substrate-specific toxicity (e.g., bleeding, oversedation).
Contraindications & Cautions
Absolute Contraindications (per FDA Label)
- Narcolepsy — orexin antagonism could exacerbate the underlying loss of orexin signaling that produces the disorder.
- Hypersensitivity to daridorexant or any component of QUVIVIQ — added in October 2023 following post-marketing reports of angioedema with pharyngeal involvement. Patients with any prior reaction should not receive daridorexant.
Not Recommended / Specialist Input Suggested
- Concomitant strong CYP3A4 inhibitors — the FDA label directs avoidance of co-administration.
- Concomitant strong or moderate CYP3A4 inducers — the FDA label directs avoidance; efficacy is substantially reduced.
- Severe hepatic impairment (Child-Pugh score ≥10) — not studied; the FDA label states daridorexant is not recommended.
- Active major depression with suicidal ideation — worsening of depression and suicidal thoughts have been reported with hypnotics. Prescribe the smallest feasible quantity per label.
- Pediatric patients — safety and effectiveness have not been established.
- Combination with other hypnotics — the FDA label specifically states use of daridorexant with other drugs to treat insomnia is not recommended.
Use with Caution
- Older adults — likelihood of somnolence and fatigue increases with age; falls risk should be considered before escalation to 50 mg.
- Moderate hepatic impairment (Child-Pugh B, score 7–9) — maximum dose 25 mg.
- Concomitant moderate CYP3A4 inhibitor — maximum 25 mg.
- Compromised respiratory disease (OSA, COPD) — studied in mild–severe OSA (without CPAP) and moderate COPD; not studied in mild or severe COPD. Respiratory effects cannot be excluded.
- History of substance use disorder — Schedule IV; abuse liability at supratherapeutic doses comparable to zolpidem and high-dose suvorexant.
- Patients who cannot guarantee 7 hours of sleep opportunity — risk of next-day impairment is materially increased.
- Pregnancy and lactation — no human data are available. Animal reproduction studies showed no fetal toxicity at up to 8–10× MRHD. Daridorexant and metabolites are present in rat milk; monitor breastfed infants for excessive sedation. A pregnancy exposure registry is available (1-833-400-9611).
In April 2019, the FDA required a Boxed Warning on eszopiclone, zaleplon, and zolpidem for rare but serious complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating, and others) that have resulted in injuries and deaths. Daridorexant was approved in January 2022 — after the 2019 Boxed Warning — and is not included in it, but its FDA label states that complex sleep behaviors have been reported with hypnotics including DORAs and directs immediate discontinuation if any patient experiences such an episode. The risk is increased by alcohol and other CNS depressants. Counsel every patient on this risk before the first dose.
Patient Counselling
Purpose of Therapy
Daridorexant is approved for adults with insomnia involving difficulty falling asleep, staying asleep, or both. It works differently from older sleeping pills: rather than enhancing the brain’s sleep-promoting signals, it blocks the brain’s own wake-promoting signals (orexin). Compared with the other drugs in the same class, daridorexant has a relatively short duration of action and was specifically designed to reduce next-day grogginess. It is a federally controlled substance because it can be misused; keep it in a secure place and do not share it. Cognitive behavioural therapy for insomnia (CBT-I) remains the recommended first-line treatment for chronic insomnia and should ideally be offered or continued alongside any drug therapy.
How to Take It
Take one tablet in the evening within 30 minutes of going to bed, and only when you can stay in bed for at least 7 hours before being active again. The recommended dose is either 25 mg or 50 mg, chosen by your prescriber. Avoid taking it with or shortly after a heavy or fatty meal — food, especially a high-fat dinner, slows how quickly the medication starts working by about 1–2 hours, although the total amount of medication absorbed is unchanged. Do not drink alcohol on evenings you take daridorexant.
Sources
- U.S. Food and Drug Administration. Quviviq (daridorexant) prescribing information — current label revised September 2024 (Reference ID 5454933; supplement s011); initial approval January 2022 (Reference ID 4901828). accessdata.fda.gov Authoritative US label — primary source for indications, dosing, contraindications, drug interactions, and incidence figures cited throughout this monograph. Includes hypersensitivity contraindication added October 2023 and updated respiratory function section September 2024.
- DailyMed (NIH). QUVIVIQ (daridorexant) tablet, film coated — current label. dailymed.nlm.nih.gov Searchable, regularly updated mirror of the FDA-approved labeling, including current PLLR-format Pregnancy and Lactation sections.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA adds Boxed Warning for risk of serious injuries caused by sleepwalking with certain prescription insomnia medicines. April 30, 2019. fda.gov FDA communication clarifying that the 2019 Boxed Warning applies to eszopiclone, zaleplon, and zolpidem; daridorexant — approved in 2022 — is not included.
- Mignot E, Mayleben D, Fietze I, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022;21(2):125–139. doi: 10.1016/S1474-4422(21)00436-1 Pivotal Phase 3 program (Studies 1 and 2; 1,854 adults across 156 sites in 17 countries) demonstrating efficacy on objective polysomnographic LPS and WASO and — uniquely among insomnia drugs — patient-reported daytime functioning at the 50 mg dose using the IDSIQ.
- Zammit G, Dauvilliers Y, Pain S, et al. Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia disorder. Neurology. 2020;94(21):e2222–e2232. doi: 10.1212/WNL.0000000000009475 Phase 2 dose-finding study in elderly patients with insomnia, supporting the 25 mg and 50 mg doses chosen for the Phase 3 program.
- Kunz D, Dauvilliers Y, Benes H, et al. Long-term safety and tolerability of daridorexant in patients with insomnia disorder. CNS Drugs. 2023;37(1):93–106. doi: 10.1007/s40263-022-00980-8 Long-term (9-month) extension trial (Study 3) following Studies 1 and 2; supports 12-month tolerability with no evidence of physical dependence or rebound insomnia.
- Fietze I, Bassetti CLA, Mayleben DW, et al. Efficacy and safety of daridorexant in older and younger adults with insomnia disorder: a secondary analysis of a randomised placebo-controlled trial. Drugs Aging. 2022;39(10):795–810. doi: 10.1007/s40266-022-00977-4 Pre-specified subgroup analysis of the pivotal trials in patients ≥65 years; supports preserved efficacy and tolerability in older adults at recommended doses.
- Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307–349. doi: 10.5664/jcsm.6470 AASM 2017 guideline; pre-dates daridorexant approval (January 2022) and therefore does not include a specific recommendation for it.
- Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125–133. doi: 10.7326/M15-2175 ACP guideline emphasising CBT-I as first-line treatment for chronic insomnia, with pharmacotherapy reserved for patients in whom CBT-I is inadequate or unavailable.
- Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675–700. doi: 10.1111/jsr.12594 European Sleep Research Society guideline; concordant with US recommendations on CBT-I as first-line therapy.
- Treiber A, de Kanter R, Roch C, et al. The use of physiology-based pharmacokinetic and pharmacodynamic modeling in the discovery of the dual orexin receptor antagonist ACT-541468. J Pharmacol Exp Ther. 2017;362(3):489–503. doi: 10.1124/jpet.117.241596 Discovery and PK/PD modelling paper for daridorexant (originally ACT-541468) — explains the rational selection of an ~8-hour half-life to minimise next-day residual effects.
- Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007;8(3):171–181. doi: 10.1038/nrn2092 Foundational review of orexin signalling and its role in arousal — the conceptual basis for orexin antagonism as a hypnotic strategy.
- Markham A. Daridorexant: first approval. Drugs. 2022;82(5):601–607. doi: 10.1007/s40265-022-01699-y Adis review summarising the regulatory development, pharmacology, and key clinical data supporting the 2022 FDA approval.
- Muehlan C, Boehler M, Brooks S, Zuiker R, van Gerven J, Dingemanse J. Clinical pharmacology of the dual orexin receptor antagonist ACT-541468 in elderly subjects: exploration of pharmacokinetics, pharmacodynamics and tolerability following single-dose morning and repeated-dose evening administration. J Psychopharmacol. 2020;34(3):326–335. doi: 10.1177/0269881119882854 Phase 1 study characterising daridorexant pharmacokinetics, pharmacodynamics, and tolerability in healthy elderly subjects — informs the lack of formal dose adjustment for older adults in the current label.