Pitolisant
Wake-promoting agents and narcolepsy drugs
Wake-promoting agents and narcolepsy drugs
A histamine H3 receptor blocker for daytime sleepiness and cataplexy in narcolepsy. It can prolong the QT interval and weaken hormonal contraceptives.
Quick facts
- Group
- Wake-promoting agents and narcolepsy drugs
- Target
- Histamine H3 receptor
- Used for
- Excessive daytime sleepiness
- Key effects
- Headache · Insomnia · Nausea and less appetite
- Monitor
- ECG and potassium · Daytime sleepiness
- ATC
- N07XX11
No doses: the clinician sets them by the current guideline.
Mechanism of action
Pitolisant is a selective antagonist and inverse agonist of the histamine H3 receptor, which normally acts as a brake on histamine release in the brain. Blocking it lets histaminergic neurons release more histamine, a key wake-promoting signal. It has little affinity for H1, H2 or H4 receptors.
- Blocks the H3 autoreceptor on histamine neurons
- The brake is released and more histamine is set free
- Wakefulness rises; sleepiness and cataplexy decrease
Indications
- Excessive daytime sleepiness in narcolepsy (adults and children from 6 years) Narcolepsy →
- Cataplexy in adults with narcolepsy
Adverse effects
Common
- Headache
- Insomnia
- Nausea and less appetite
- Anxiety and irritability
Contraindications
- Liver disease, which can rule it out
- Hypersensitivity to pitolisant
Key interactions
- Hormonal contraceptives
- Less effective; another method is used during treatment and for 21 days after
- Other drugs that prolong the QT interval
- Added risk of arrhythmia
What is monitored
- ECG and potassium and magnesium when there is QT risk
- Daytime sleepiness and cataplexy episodes
Administration and safety
- Given by mouth, starting low and raising the dose step by step
- Liver and kidney disease are reviewed before starting
Pregnancy and breastfeeding
It weakens hormonal contraceptives, so another method is used; pregnancy plans are discussed with the prescriber.
Nursing care
- Ask about heart rhythm problems, low potassium or magnesium and liver disease
- Counsel on non-hormonal contraception during treatment and for 21 days after
- Teach to report palpitations, fainting or hallucinations
Pharmacokinetics
- Metabolism
- In the liver; CYP2D6 genotype can change the dose needed
Test yourself
Think of the answer, then tap the question to see it.
What does the H3 receptor normally do?
It is an autoreceptor that brakes histamine release.
Which ECG change is a concern with pitolisant?
QT prolongation.
For how long after stopping pitolisant is another contraceptive method used?
For 21 days.
Connections
← Back to the class: Wake-promoting agents and narcolepsy drugs
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Pitolisant: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.