Products
Pitolisant (formerly tiprolisant) is commercially available in the form of film-coated tablets (Wakix). It was approved in the EU in 2016, in many countries in 2018, and in the United States in 2019.
Structure and properties
Pitolisant (C17H26ClNO, Mr = 295.8 g/mol) is a piperidine derivative and an ether.
Effects
Pitolisant (ATC N07XX11) is an inverse agonist/antagonist at the histamine H3 receptor. It promotes histaminergic signaling in the brain and also increases the release of acetylcholine, norepinephrine, and dopamine. This increases alertness and attention. The histamine H3 receptor is an autoreceptor that inhibits the release of histamine in the central nervous system. The half-life is 10 to 12 hours.
Indications
In adults, for the treatment of narcolepsy with or without cataplexy.
Dosage
According to the professional information. The dose is adjusted individually. Tablets are taken in the morning with breakfast.
Contraindications
- Hypersensitivity
- Severe liver dysfunction
- Breastfeeding
Full precautions can be found in the drug label.
Interactions
Pitolisant is a substrate of CYP3A4 and CYP2D6. Drug-drug interactions have been described with the following agents and others:
- Tri- and tetracyclic antidepressants.
- Antihistamines, which cross the blood–brain barrier.
- Agents that prolong the QT interval.
- Enzyme inducers
- CYP2D6 inhibitors
Adverse effects
The most common possible adverse effects include insomnia, headache, and nausea.
