Pitolisant for treating patients with narcolepsy

ABSTRACT

Introduction: Narcolepsy is a rare sleep disorder characterized by excessive daytime sleepiness, cataplexy, disturbed nocturnal sleep, hypnagogic hallucinations, and sleep paralysis. Pitolisant is a first-in-class drug acting on histamine 3 receptors and indicated for the treatment of narcolepsy. This article aims to review pitolisant.

Areas covered: In this paper the chemical properties, mechanism of action, pharmacokinetics, clinical efficacy and safety of pitolisant was introduced, and the development course of drugs for treating narcolepsy is also briefly described. We performed a systematic review of the literature using PubMed and the following keywords were used: ‘pitolisant’ and ‘narcolepsy’, ‘cataplexy’ and ‘excessive daytime sleepiness’ and ‘histamine 3 receptor’.

Expert opinion: Pitolisant is a histamine 3 receptor antagonist/inverse agonist. It can activate histamine release in the brain and enhances wakefulness. Clinical studies showed that pitolisant significantly decreased excessive daytime sleepiness and cataplexy rate versus placebo. Pitolisant was well tolerated, common adverse reactions were headache, insomnia, nausea, and anxiety.

KEYWORDS:

• Cataplexy
• excessive daytime sleepiness
• histamine 3 receptor
• inverse agonist
• narcolepsy
• pitolisant

Article highlights

• Pitolisant is a histamine-3 receptor antagonist/inverse agonist.

• Pitolisant can activate histamine release in the brain, enhances wakefulness.

• Pitolisant was approved by the EMA for the treatment of narcolepsy with or without cataplexy, and was approved by the US FDA for the treatment of EDS in adult patients with narcolepsy.

• The US FDA recommend dosage range for pitolisant is 17.8 mg to 35.6 mg administered orally once daily.

• Common adverse reactions of pitolisant were headache, insomnia, nausea, and anxiety.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer has received honoraria for consultancy from: Bioprojet Pharma, Harmony Bioscience, UCB Pharma, Takeda, & Jazz Pharmaceuticals. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript was not funded