daridorexant

General

Pronunciation:
dar-i-doe-rex-ant

Trade Name(s)

  • Quviviq

Ther. Class.

sedative/hypnotics

Pharm. Class.

orexin receptor antagonists

Controlled Substance Schedule: IV

Indications

Insomnia associated with difficulty in sleep onset and/or maintenance.

Action

Antagonizes the effects of orexins A and B, naturally occurring neuropeptides that promote wakefulness, by binding to their receptors.

Therapeutic Effect(s):

Improved sleep.

Pharmacokinetics

Absorption: 62% absorbed following oral administration; a high-fat meal will delay absorption and sleep onset.

Distribution: Well distributed to tissues.

Protein Binding: 99.7%.

Metabolism and Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme. Primarily excreted as metabolites in the feces (57%), with some excretion in the urine (28%).

Half-life: 8 hr.

TIME/ACTION PROFILE (sleep)

ROUTEONSETPEAKDURATION
PO30 minunknown6 hr†
†Excess sedation may persist for several days after discontinuation.

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Narcolepsy;
  • Severe hepatic impairment.

Use Cautiously in:

  • History of substance abuse or drug dependence;
  • Depression;
  • Underlying pulmonary disease;
  • Moderate hepatic impairment (↓ dose);
  • OB:   Safety not established in pregnancy;
  • Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
  • Pedi:  Safety and effectiveness not established in children;
  • Geri:  ↑ risk of falls in older adults.

Adverse Reactions/Side Effects

GI: nausea, vomiting

Neuro: drowsiness, cataplexy, complex sleep behaviors (including sleep driving, sleep walking, or engaging in other activities while sleeping), dizziness, hallucinations (during sleep), headache, sleep paralysis, SUICIDAL IDEATION, worsening of depression

Misc: hypersensitivity reactions (including angioedema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  •  Strong CYP3A4 inhibitors, including  itraconazole, ↑ levels and risk of toxicity; concurrent use not recommended.
  •  Moderate CYP3A4 inhibitors, including  diltiazem, may ↑ levels and risk of toxicity; ↓ daridorexant dose.
  •  Strong CYP3A4 inducers, including  rifampin, and  moderate CYP3A4 inducers, including  efavirenz, ↓ levels and effectiveness; concurrent use not recommended.
  • Risk of CNS depression, next-day impairment, sleep-driving, and other complex behaviors while not fully awake ↑ with other  CNS depressants, including  alcohol, some  antihistamines,  opioids, other  sedative/hypnotics  (including  benzodiazepines ), and  tricyclic antidepressants ; concurrent alcohol use should be avoided; for patients receiving other CNS depressants, dose adjustments of daridexorant and/or CNS depressants may be necessary.

Route/Dosage

PO (Adults): 25–50 mg within 30 min of going to bed; dose may not be repeated on a single night and should be taken when ≥7 hr of sleep time is anticipated before planned awakening.  Concurrent use of moderate CYP3A4 inhibitors:  25 mg within 30 min of going to bed; dose may not be repeated on a single night and should be taken when ≥7 hr of sleep time is anticipated before planned awakening.

Hepatic Impairment 
PO (Adults): Moderate hepatic impairment:  25 mg within 30 min of going to bed; dose may not be repeated on a single night and should be taken when ≥7 hr of sleep time is anticipated before planned awakening.

Availability

Tablets: 25 mg, 50 mg

Assessment

  • Assess sleep patterns prior to and during administration. Continued insomnia after 7–10 days of therapy may indicate primary psychiatric or mental illness.
  • Assess mental status and potential for abuse prior to administration. Prolonged use of >7–10 days may lead to physical and psychological dependence. Limit amount of drug available to the patient.
  • Monitor for signs and symptoms of hypersensitivity reactions (angioedema, rash, urticaria) during therapy. If severe reaction occurs, treat symptomatically and discontinue daridorexant.

Implementation

  • PO Administer within 30 min of going to bed with ≥7 hr remaining prior to planned awakening. Time to sleep onset may be delayed if taken with or soon after a meal.

Patient/Family Teaching

  • Instruct patient to take daridorexant within 30 min of going to bed, as directed. Do not take daridorexant if alcohol was consumed that evening. Do not increase dose or discontinue without notifying health care professional. CNS-depressant effects may persist in some patients for up to several days after discontinuing. Advise patient to read  Medication Guide  before starting therapy and with each Rx refill in case of changes.
  • May cause daytime and next-day drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
  • Caution patient that daridorexant may cause complex sleep behaviors (sleep walking, sleep driving, making and eating food, talking on the phone, having sex) while unaware. Patient may not remember anything done during the night; increased risk with alcohol or other CNS depressants. Discontinue daridorexant immediately and notify health care professional if complex sleep behaviors occur.
  • Inform patients and their families that daridorexant may cause sleep paralysis, an inability to move or speak for several min during sleep-wake transitions and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions.
  • Advise patient that daridorexant is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
  • Caution patient to avoid concurrent use of alcohol or other CNS depressants, including opioids.
  • Advise patient to notify health care professional if signs and symptoms of allergic reaction (swelling of tongue or throat, trouble breathing, nausea and vomiting) occur.
  • Rep:  Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Infants exposed to daridorexant through breast milk should be monitored for excessive sedation. Inform females there is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to daridorexant during pregnancy. Pregnant women exposed to daridorexant and health care professionals are encouraged to call Idorsia Pharmaceuticals Ltd at 1-833-400-9611.

Evaluation/Desired Outcomes

Improved sleep.