|Other names||Tiprolisant; Ciproxidine; BF2.649|
|Drug class||Histamine H3 receptor inverse agonists|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||295.85 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
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Pitolisant, sold under the brand name Wakix, is a medication for the treatment of excessive daytime sleepiness (EDS) in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist. It represents the first commercially available medication in its class. Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness.
The most common side effects include difficulty sleeping, nausea, and feeling worried.
Pitolisant is used in adults for the treatment of excessive daytime sleepiness in people with narcolepsy, with or without cataplexy. Narcolepsy is a sleep problem that is characterized by an irresistible urge to sleep and disturbed nighttime sleep, while cataplexy refers to attacks of severe muscle weakness that cause a person to collapse.
The most common side effects include insomnia (difficulty sleeping), headache, nausea (feeling sick), anxiety, irritability, dizziness, depression, tremor, sleep disorders, tiredness, vomiting, vertigo (a spinning sensation) and dyspepsia (heartburn). Serious but rare side effects are abnormal loss of weight and spontaneous abortion.
Pitolisant was developed by Jean-Charles Schwartz, Walter Schunack, and colleagues after the former discovered the H₃ receptor. It was the first H₃ receptor inverse agonist to be tested in humans or introduced for clinical use. It was designed and developed by Bioprojet, who has marketed the product in Europe since its approval by the European Medicines Agency in 2016.
The FDA approved pitolisant for excessive daytime sleepiness in participants with narcolepsy based primarily on evidence from two trials (Trial 1/NCT 01067222, Trial 2/NCT 01638403). An additional trial (Trial 3/NCT01800045), in which participants with a different type of narcolepsy were exposed to the same dose of pitolisant, was used to add data for evaluation of side effects. The trials were conducted in Europe and South America.
The two primary trials enrolled adults with narcolepsy and excessive daytime sleepiness. Participants received pitolisant, placebo, or an approved drug for narcolepsy for eight weeks. For participants receiving pitolisant, the dose could be increased during the first three weeks but had to remain the same for the next five weeks. Neither the participants nor the healthcare providers knew which treatment was being given during the trial.
The benefit of pitolisant was evaluated by comparing changes in daytime sleepiness during the trial between pitolisant- and placebo-treated participants. To measure the daytime sleepiness, the investigators used a scale called the Epworth Sleepiness Scale (ESS). The ESS asks participants to rate the likelihood that they would fall asleep while doing eight daily activities (such as sitting and reading or watching television). Participants rate each item from zero (would never doze) to three (high chance of dozing).
Pitolisant was approved by the U.S. Food and Drug Administration (FDA) in August 2019. It was granted orphan drug designation for the treatment of narcolepsy, fast track designation for the treatment of excessive daytime sleepiness (EDS) and cataplexy in people with narcolepsy, and breakthrough therapy designation for the treatment of cataplexy in people with narcolepsy. Pitolisant represents the first new therapy in the U.S. in over fifteen years for the treatment of both EDS and cataplexy in adults with narcolepsy.[medical citation needed]
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- "Wakix EPAR". European Medicines Agency (EMA). Retrieved 18 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- "FDA Approves Pitolisant for Daytime Sleepiness in Patients with Narcolepsy". Pharmacy Times. Retrieved 18 August 2020.
- Syed YY (20 July 2016). "Pitolisant: First Global Approval". Drugs. 76 (13): 1313–1318. doi:10.1007/s40265-016-0620-1. PMID 27438291. S2CID 42684839.
- "Drug Trials Snapshots: Wakix". U.S. Food and Drug Administration (FDA). 14 August 2019. Retrieved 18 March 2020. This article incorporates text from this source, which is in the public domain.
- "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.
- Schwartz JC (2011). "The histamine H3 receptor: from discovery to clinical trials with pitolisant". Br. J. Pharmacol. 163 (4): 713–21. doi:10.1111/j.1476-5381.2011.01286.x. PMC 3111674. PMID 21615387.
- "Pitolisant". Drug Information Portal. U.S. National Library of Medicine.
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