Daridorexant
Other hypnotics (melatonin agonists and orexin antagonists)
Other hypnotics (melatonin agonists and orexin antagonists)
An orexin receptor antagonist for insomnia that blocks the brain's wake signal. Next-day drowsiness and sleep paralysis are possible; avoided in narcolepsy.
Quick facts
- Group
- Other hypnotics (melatonin agonists and orexin antagonists)
- Target
- Orexin receptors (OX1 shown)
- Used for
- Insomnia with trouble falling
- Key effects
- Headache · Fatigue and daytime sleepiness
- Monitor
- Next-day alertness · Mood and behaviour changes
- ATC
- N05CJ03
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows daridorexant itself bound to the human OX1 orexin receptor.
Daridorexant is an orexin receptor antagonist. It blocks the receptors for orexin, a neuropeptide that keeps the brain awake, so the wake drive falls at night and sleep can begin and continue.
- Blocks orexin receptors in the brain
- The orexin wake drive falls
- Sleep begins and is maintained
Indications
- Insomnia with trouble falling or staying asleep Insomnia disorder →
Adverse effects
Common
- Headache
- Fatigue and daytime sleepiness
- Dizziness and nausea
Contraindications
- Narcolepsy
Key interactions
- Alcohol
- Worse side effects
- St John's wort
- May change how well it works
- Grapefruit
- May change its levels; discussed with the prescriber
What is monitored
- Next-day alertness, driving and falls in older adults
- Mood and behaviour changes
Administration and safety
- Given by mouth, at most once a night, shortly before bedtime
- No driving until fully awake the next day
- Controlled medicine
Nursing care
- Ask about narcolepsy, COPD, sleep apnoea and liver disease
- Teach to avoid alcohol
- Teach to report sleep paralysis, hallucinations, leg weakness or actions done while asleep
Pharmacokinetics
- Onset and duration
- Taken about half an hour before bedtime, so it acts at sleep onset
Test yourself
Think of the answer, then tap the question to see it.
What does daridorexant block?
Orexin receptors, which carry the brain's wake signal.
Which sleep disorder makes it unsuitable?
Narcolepsy.
Which night-time adverse effects resemble narcolepsy symptoms?
Sleep paralysis and hallucinations on falling asleep or waking (also cataplexy-like leg weakness).
Connections
← Back to the class: Other hypnotics (melatonin agonists and orexin antagonists)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Daridorexant: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); 6TP3: Crystal structure of the Orexin-1 receptor in complex with daridorexant (RCSB Protein Data Bank, 2020); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.