|Trade names||Wakix, Ozawade, others|
|Other names||Tiprolisant; Ciproxidine; BF2.649|
|Drug class||Histamine 3 (H3) receptor inhibitor|
|Main uses||Excessive daytime sleepiness in narcolepsy|
|Side effects||Headache, trouble sleeping, nausea, anxiety|
|Typical dose||4.5 to 36 mg OD|
|Chemical and physical data|
|Molar mass||295.85 g·mol−1|
|3D model (JSmol)|
Common side effects include headache, trouble sleeping, nausea, and anxiety. Other side effects may include QT prolongation. Safety in pregnancy is unclear. It bring about an opposite to usual response at the histamine 3 (H3) receptor. This increases the activity of histamine neurons in the brain, which keeps a person awake.
Pitolisant was approved for medical use in the United States in 2019 and Europe in 2021. In the United Kingdom it costs the NHS about £310 per month as of 2021. In the United States this amount costs about 6,800 USD.
Pitolisant is used in adults for the treatment of excessive daytime sleepiness. 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. Pitolisant (Ozawade) is indicated to improve wakefulness and reduce excessive daytime sleepiness in adults with obstructive sleep apnea.
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 is marketed in the European Union by Bioprojet Pharma. It was approved for medical use in the European Union in March 2016.
The FDA approved pitolisant for excessive daytime sleepiness in participants with narcolepsy based primarily on evidence from two trials (Trial 1/NCT01067222, Trial 2/NCT01638403). 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 and cataplexy in people with narcolepsy, and breakthrough therapy designation for the treatment of cataplexy in people with narcolepsy.
- "Wakix- pitolisant hydrochloride tablet, film coated". DailyMed. 6 November 2019. Archived from the original on 11 August 2020. Retrieved 18 August 2020.
- "Ozawade EPAR". European Medicines Agency (EMA). Archived from the original on 15 October 2021. Retrieved 15 October 2021.
- BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 513. ISBN 978-0857114105.
- "Wakix EPAR". European Medicines Agency (EMA). Archived from the original on 12 November 2020. Retrieved 18 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- "Pitolisant Monograph for Professionals". Drugs.com. Archived from the original on 21 January 2021. Retrieved 28 October 2021.
- "Pitolisant (Wakix) Use During Pregnancy". Drugs.com. Archived from the original on 18 March 2020. Retrieved 28 October 2021.
- 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.
- "Wakix Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 24 January 2021. Retrieved 28 October 2021.
- 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.
- "Drug Trials Snapshots: Wakix". U.S. Food and Drug Administration (FDA). 14 August 2019. Archived from the original on 22 December 2020. Retrieved 18 March 2020. This article incorporates text from this source, which is in the public domain.
- "Pitolisant Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 17 May 2010. Archived from the original on 26 May 2021. Retrieved 25 May 2021.
- "Harmony's pitolisant granted breakthrough and fast track designations". Pharma Business International. 22 May 2018. Archived from the original on 26 May 2021. Retrieved 25 May 2021.
- "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Archived from the original on 16 September 2020. Retrieved 15 September 2020.