Daridorexant: dose, uses and side effects

Daridorexant (nemorexant) is a newer class of sedative-hypnotic drugs under non-benzodiazepine category. it is used to treat insomnia in adults. daridorexant blocks binding of wake promoting neuropeptides (orexin A and orexin B) to its receptors OX-1 and OX-2. It should be avoided in patients with depression.

Drug class

Orexin receptor antagonist, hypnotics

Available preparation

Daridorexant hydrochloride (also known as nemorexant hydrochloride)

Tablet: 25 mg, 50 mg

Dosage

  • Adult: 25 – 50 mg (30 min before bedtime)
  • Children: not recommended

Common use

Insomnia (sleep initiation and maintenance disorder)

Side effects

  • Worsening of depression, suicidal thoughts
  • Hypnogogic/hypnopompic hallucination
  • Daytime sleepiness, so avoided in pts requiring continuous attention like driving
  • Cataplexy like symptoms, so avoided with alcohol
  • Abuse potential/ physical dependence develops on long term use

Contraindicated in pts with narcolepsy (sleep paralysis) and compromised respiratory function.

Overdose causes muscle weakness, sleep paralysis, catalepsy, headache, constipation.

Pharmacological characteristics

  • Onset of action: 30 min with peak plasma concentration in 1-2 hours.
  • Half-life (t1/2): 8 hours
  • Duration of action: 7-10 hours
  • MOA: blocking the binding of wake promoting neuropeptides (orexin A and orexin B) to its receptors OX-1 and OX-2
  • Oral bioavailability: 62%
  • No QT-interval prolongation (at a dose of 4 times the max recommended dose)
  • Metabolized by CYP 3A4 enzyme, so avoided concomitant use of strong CYP enzyme inducers and inhibitors.
  • Inactive metabolites are excreted in feces (57%) and urine (28%)
  • Safety and effectiveness have not been established during pregnancy and lactation.
  • No fetal toxicity/malformation observed on animal study.

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