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Pronunciation | /pɪˈtɒlɪsənt/ pi-TOL-i-sənt |
Trade names | Wakix, Ozawade |
Other names | Tiprolisant; Ciproxidine; BF2.649 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a619055 |
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Routes of administration | By mouth |
Drug class | Histamine H3 receptor inverse agonists |
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Formula | C17H26ClNO |
Molar mass | 295.85 g·mol−1 |
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Pitolisant, sold under the brand name Wakix among others, is a medication used for the treatment of excessive daytime sleepiness in adults with narcolepsy.[2] It is a histamine 3 (H3) receptor antagonist/inverse agonist.[2] It represents the first commercially available medication in its class, so that the US Food and Drug Administration (FDA) declares it a first-in-class medication.[6][7] Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness.[8]
The most common side effects include difficulty sleeping, nausea, and feeling worried.[9]
Pitolisant is indicated in adults for the treatment of narcolepsy.[2][3] Narcolepsy is a chronic sleep disorder that causes overwhelming daytime drowsiness.[3] Pitolisant is also indicated to improve alertness and reduce excessive daytime sleepiness in adults with obstructive sleep apnea.[4]
The most common side effects include insomnia, headache, nausea, anxiety, irritability, dizziness, depression, tremor, sleep disorders, tiredness, vomiting, vertigo, and dyspepsia (heartburn).[3] Rare but serious side effects are abnormal loss of weight and spontaneous abortion.[3]
Pitolisant is an inverse agonist of the histamine 3 (H3) autoreceptor. The H3 autoreceptors regulate histaminergic activity in the central nervous system (and to a lesser extent, the peripheral nervous system) by inhibiting histamine synthesis and release upon binding to endogenous histamine.[10] By preventing the binding of endogenous histamine at the H3, as well as producing a response opposite to that of endogenous histamine at the receptor (inverse agonism), pitolisant enhances histaminergic activity in the brain.[11]
Pitolisant is marketed in the European Union by Bioprojet Pharma.[3] It was approved for medical use in the European Union in March 2016.[3]
The US Food and Drug Administration (FDA) approved pitolisant for excessive daytime sleepiness in participants with narcolepsy based primarily on evidence from two trials (Trial 1/NCT01067222, Trial 2/NCT01638403).[9] 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.[9] The trials were conducted in Europe and South America.[9]
The two primary trials enrolled adults with narcolepsy and excessive daytime sleepiness.[9] Participants received pitolisant, placebo, or an approved drug for narcolepsy for eight weeks.[9] 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.[9] Neither the participants nor the healthcare providers knew which treatment was being given during the trial.[9]
The benefit of pitolisant was evaluated by comparing changes in daytime sleepiness during the trial between pitolisant- and placebo-treated participants.[9] To measure the daytime sleepiness, the investigators used a scale called the Epworth Sleepiness Scale (ESS).[9] 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).[9] Participants rate each item from zero (would never doze) to three (high chance of dozing).[9]
Pitolisant was approved by the FDA in August 2019.[9] It was granted orphan drug designation for the treatment of narcolepsy,[12] 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.[13]
Pitolisant is approved in the European Union and the United States to treat narcolepsy, and is not a controlled substance in these countries.[failed verification] Still, long-term studies comparing the effectiveness and tolerability of pitolisant with modafinil or sodium oxybate are lacking.[failed verification] Pitolisant, the only non-controlled anti-narcoleptic drug in the US,[14] has shown minimal abuse risk in studies.[14][15]