Daridorexant: Drug information

For additional information see "Daridorexant: Patient drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Quviviq

Brand Names: Canada

Quviviq

Pharmacologic Category

Hypnotic, Miscellaneous;
Orexin Receptor Antagonist

Dosing: Adult

Note: In general, limit long-term use (>4 weeks) of insomnia medications to cases for which nonpharmacologic treatments are unavailable or ineffective and benefits are felt to outweigh risks (Ref). In one study, daridorexant was well tolerated and provided sustained efficacy over the course of 1 year (Ref).

Insomnia, sleep onset or sleep maintenance

Insomnia, sleep onset or sleep maintenance: Oral: 25 to 50 mg once daily within 30 minutes of bedtime and at least 7 hours before planned time of awakening. Maximum: 50 mg/day (Ref).

Canadian labeling: 50 mg once daily within 30 minutes of bedtime and at least 7 hours before planned time of awakening. Some patients may require 25 mg once daily within 30 minutes of bedtime (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

No dosage adjustment necessary.

Dosing: Liver Impairment: Adult

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate impairment (Child-Pugh class B): Maximum 25 mg/day.

Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations

CNS depression

Daridorexant is frequently associated with CNS depression, including daytime sedation, drowsiness, and fatigue, which may impair driving.

Mechanism: Dose-related; related to the pharmacologic action via orexin receptor antagonism which is believed to suppress wake drive (Ref).

Onset: Rapid; sleep onset occurs within 30 to 40 minutes (Ref). CNS-depressant effects may persist for up to several days after discontinuing use.

Risk factors:

• Daytime impairment is increased with less than a full night of sleep (ie, <7 hours)

• Higher than recommended doses

• Concomitant administration with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol)

• Older adults (risk of falling)

Complex sleep behaviors

Events associated with complex sleep disorders, including hazardous sleep-related activities such as sleepwalking, sleep-driving, cooking and eating food, making phone calls, or having sex while asleep have been reported with other orexin receptor antagonists at therapeutic doses, with or without concomitant use of alcohol or other CNS depressants. Patients do not usually remember these events.

Onset: Varied; can occur at any time (following the first dose or any subsequent doses).

Sleep-related effects

Daridorexant may infrequently cause hallucinations (hypogenic hallucinations and hypnopompic hallucinations), abnormal dreams, and nightmares. In addition, sleep paralysis (inability to move or speak for several minutes during sleep-wake transitions) may occur. Mild cataplexy occurring during the night or day has been reported with other orexin receptor antagonists, and is not always associated with a triggering event (eg, laughter, surprise).

Mechanism: Unknown whether these events are specifically related to antagonism of orexin receptors; however, orexin neuron loss is associated with the symptoms of narcolepsy which suggests orexin receptor antagonists can theoretically produce narcolepsy symptoms, particularly cataplexy (Ref).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.

1% to 10%:

Gastrointestinal: Nausea (3%)

Nervous system: Dizziness (3%), drowsiness (≤6%) (table 1)Drowsiness, fatigue (≤6%) (table 2)Fatigue, headache (6% to 7%)

**Daridorexant: Adverse Reaction: Drowsiness**
Drug (Daridorexant)	Placebo	Dose	Number of Patients (Daridorexant)	Number of Patients (Placebo)	Comments
6%	4%	25 mg once daily	310	309	Described as "somnolence or fatigue"
5%	4%	50 mg once daily	308	309	Described as "somnolence or fatigue"

**Daridorexant: Adverse Reaction: Fatigue**
Drug (Daridorexant)	Placebo	Dose	Number of Patients (Daridorexant)	Number of Patients (Placebo)	Comments
6%	4%	25 mg once daily	310	309	Described as "somnolence or fatigue"
5%	4%	50 mg once daily	308	309	Described as "somnolence or fatigue"

<1%: Nervous system: Hallucination (hypnogenic hallucinations and hypnopompic hallucinations) (table 3)Hallucination, sleep paralysis (table 4)Sleep Paralysis

**Daridorexant: Adverse Reaction: Hallucination**
Drug (Daridorexant)	Placebo	Dose	Number of Patients (Daridorexant)	Number of Patients (Placebo)	Comments
0.6%	0%	25 mg once daily	310	309	Hypnagogic and hypnopompic hallucinations

**Daridorexant: Adverse Reaction: Sleep Paralysis**
Drug (Daridorexant)	Placebo	Dose	Number of Patients (Daridorexant)	Number of Patients (Placebo)
0.5%	0%	25 mg once daily	310	309
0.3%	0%	50 mg once daily	308	309

Frequency not defined: Nervous system: Daytime sedation (including driving impairment)

Postmarketing:

Hypersensitivity: Hypersensitivity reaction (including angioedema)

Nervous system: Abnormal dreams (including nightmares)

Contraindications

History of hypersensitivity (eg, angioedema with pharyngeal involvement) to daridorexant or any component of the formulation; narcolepsy.

Warnings/Precautions

Disease-related concerns:

• Depression: Use with caution in patients with depression; worsening of depression, including suicide or suicidal ideation, has been reported with the use of hypnotics.

• Hepatic impairment: Use with caution in patients with moderate hepatic impairment (Child-Pugh class B); frequency and severity of adverse reactions may be increased. Use is not recommended in patients with severe hepatic impairment (Child-Pugh class C).

• Respiratory disease: Consider the effects of daridorexant on respiratory function in patients with respiratory compromise; has not been studied in patients with mild or severe chronic obstructive pulmonary disease.

Special populations:

• Older adults: Use with caution due to increased risk of somnolence, fatigue, drowsiness, and falls.

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric and/or medical illness.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Quviviq: 25 mg, 50 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Quviviq Oral)

25 mg (per each): $20.36

50 mg (per each): $20.36

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Quviviq: 50 mg

Controlled Substance

C-IV (United States); noncontrolled (Canada)

Administration: Adult

Oral: Administer within 30 minutes of bedtime with ≥7 hours remaining before planned time of awakening. Onset may be delayed if taken with or immediately after food.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/214985s010s012lbl.pdf#page=24, must be dispensed with this medication.

Use: Labeled Indications

Insomnia, sleep onset or sleep maintenance: Treatment of insomnia, characterized by difficulties with sleep onset and/or sleep maintenance, in adults.

Metabolism/Transport Effects

Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Weak), P-glycoprotein;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider Therapy Modification

Alcohol (Ethyl): May increase CNS depressant effects of Daridorexant. Risk X: Avoid

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

CNS Depressants: Daridorexant may increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification

CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor

CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor

CYP3A4 Inducers (Moderate): May decrease serum concentration of Daridorexant. Risk X: Avoid

CYP3A4 Inducers (Strong): May decrease serum concentration of Daridorexant. Risk X: Avoid

CYP3A4 Inhibitors (Moderate): May increase serum concentration of Daridorexant. Management: Limit the daridorexant dose to 25 mg, no more than once per night, when combined with moderate CYP3A4 inhibitors. Risk D: Consider Therapy Modification

CYP3A4 Inhibitors (Strong): May increase serum concentration of Daridorexant. Risk X: Avoid

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider Therapy Modification

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid

DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor

Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor

Grapefruit Juice: May increase serum concentration of Daridorexant. Management: Advise patients taking daridorexant to avoid consumption of grapefruit juice. In patients who continue to consume grapefruit juice, limit the daridorexant dose to 25 mg, no more than once per night. Risk D: Consider Therapy Modification

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider Therapy Modification

Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification

Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor

Melatonin: May increase sedative effects of Hypnotics (Nonbenzodiazepine). Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor

NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may increase CNS depressant effects of Oxybate Salt Products. Risk X: Avoid

OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor

Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification

Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification

Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor

Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor

Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Risk D: Consider Therapy Modification

Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid

Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor

Tacrolimus (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor

Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification

Ubrogepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a P-gp inhibitor. Risk D: Consider Therapy Modification

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider Therapy Modification

VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid

Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification

Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies when daridorexant was administered during the period of organogenesis to rats and rabbits in doses equivalent to 8 and 10 times the maximum recommended human dose, respectively.

Data collection to monitor pregnancy and infant outcomes following exposure to daridorexant is ongoing. Health care providers are encouraged to enroll patients exposed to daridorexant during pregnancy in the pregnancy registry (1-833-400-9611). Patients may also enroll themselves.

Breastfeeding Considerations

Daridorexant is present in breast milk.

Data related to the presence of daridorexant in breast milk are available from a study of 10 lactating patients who were exclusively breastfeeding their infants prior to the study. Following a single dose of daridorexant 50 mg, breast milk and maternal plasma were sampled at specified intervals over 72 hours. The mean age of the infants was ~86 days. The mean maximum concentration of daridorexant was 35.3 ng/mL (breast milk, range 29.9 to 41.6 ng/mL) and 1772 ng/mL (maternal plasma; range 1480 to 2121 ng/mL). Daridorexant metabolites were present in all breast milk samples for up to 24 hours after the maternal dose. Maximum daridorexant breast milk concentrations occurred ~2 hours after the dose. Using the mean maternal BMI and infant weight of the subjects, authors of the study calculated the estimated infant dose of daridorexant via breast milk to be 0.009 mg/day, providing a relative infant dose (RID) of 0.22% over the first 24 hours. Infants were not breastfed during the study. In general, breastfeeding is considered acceptable when the RID of a medication is <10% (<5% for psychotropic agents) (Kaufmann 2024).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Infants exposed via breast milk should be monitored for excessive sedation.

Monitoring Parameters

LFTs (baseline and as clinically indicated); respiratory rate (as clinically indicated).

Mechanism of Action

Daridorexant blocks the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R, which is thought to suppress wake drive (Roch 2021; manufacturer's labeling).

Pharmacokinetics (Adult Data Unless Noted)

Onset: ~35 to 40 minutes (25 mg); ~30 minutes (50 mg) (Mignot 2022).

Distribution: V_d: 31 L.

Protein binding: Plasma: 99.7%.

Metabolism: Primarily hepatic via CYP3A4 (89%).

Bioavailability: 62%.

Half-life elimination: ~8 hours.

Time to peak: 1 to 2 hours; administration with a high-fat, high-calorie meal may delay by an additional 1.3 hours.

Excretion: Feces: ~57%; urine: ~28%.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic impairment: AUC may be increased in patients with moderate hepatic impairment (has not been studied in severe hepatic impairment).

Dauvilliers Y, Zammit G, Fietze I, et al. Daridorexant, a new dual orexin receptor antagonist to treat insomnia disorder. Ann Neurol. 2020;87(3):347-356. doi:10.1002/ana.25680 [PubMed 31953863]
Herring WJ, Roth T, Krystal AD, Michelson D. Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications. J Sleep Res. 2019;28(2):e12782. doi:10.1111/jsr.12782 [PubMed 30338596]
Kaufmann P, Muehlan C, Anliker-Ort M, Sabattini G, Siebers N, Dingemanse J. Transfer of the dual orexin receptor antagonist daridorexant into breast milk of healthy lactating women. J Clin Pharmacol. 2024;64(10):1278-1287. doi:10.1002/jcph.2455 [PubMed 38736033]
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 [PubMed 36484969]
Mignot E, Mayleben D, Fietze I, et al; investigators. 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 [PubMed 35065036]
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 [PubMed 27136449]
Quviviq (daridorexant) [prescribing information]. Radnor, PA: Idorsia Pharmaceuticals US Inc; September 2024.
Quviviq (daridorexant) [product monograph]. Oakville, ON, Canada: Idorsia Pharmaceuticals Ltd; January 2024.
Refer to manufacturer's labeling.
Roch C, Bergamini G, Steiner MA, Clozel M. Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology (Berl). 2021;238(10):2693-2708. doi:10.1007/s00213-021-05954-0 [PubMed 34415378]

Topic 134764 Version 92.0

خرید پکیج

Daridorexant: Drug information