Pitolisant

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Pitolisant
Pitolisant skeletal.svg
Clinical data
Trade namesWakix, Ozawade
Other namesTiprolisant; Ciproxidine; BF2.649
AHFS/Drugs.comMonograph
MedlinePlusa619055
License data
Routes of
administration		By mouth
Drug classHistamine H3 receptor inverse agonists
ATC code
Legal status
Legal status
Identifiers
IUPAC name
  • 1-[3-[3-(4-chlorophenyl)propoxy]propyl]piperidine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC17H26ClNO
Molar mass295.85 g·mol−1
3D model (JSmol)
SMILES
  • C1CCN(CC1)CCCOCCCC2=CC=C(C=C2)Cl
InChI
  • InChI=1S/C17H26ClNO/c18-17-9-7-16(8-10-17)6-4-14-20-15-5-13-19-11-2-1-3-12-19/h7-10H,1-6,11-15H2 checkY
  • Key:NNACHAUCXXVJSP-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  

Pitolisant, sold under the brand name Wakix among others, is a medication for the treatment of excessive daytime sleepiness in adults with narcolepsy.[1] It is a histamine 3 (H3) receptor antagonist/inverse agonist.[1] It represents the first commercially available medication in its class.[4] Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness.[5]

The most common side effects include difficulty sleeping, nausea, and feeling worried.[6]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7]

Medical uses[]

Pitolisant (Wakix) is used in adults for the treatment of excessive daytime sleepiness.[1][2] 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.[2] Pitolisant (Ozawade) is indicated to improve wakefulness and reduce excessive daytime sleepiness in adults with obstructive sleep apnea.[3]

Side effects[]

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).[2] Serious but rare side effects are abnormal loss of weight and spontaneous abortion.[2]

History[]

Pitolisant was developed by Jean-Charles Schwartz, Walter Schunack, and colleagues after the former discovered the H3 receptor.[8] It was the first H3 receptor inverse agonist to be tested in humans or introduced for clinical use.[8] It is marketed in the European Union by Bioprojet Pharma.[2] It was approved for medical use in the European Union in March 2016.[2]

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).[6] 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.[6] The trials were conducted in Europe and South America.[6]

The two primary trials enrolled adults with narcolepsy and excessive daytime sleepiness.[6] Participants received pitolisant, placebo, or an approved drug for narcolepsy for eight weeks.[6] 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.[6] Neither the participants nor the healthcare providers knew which treatment was being given during the trial.[6]

The benefit of pitolisant was evaluated by comparing changes in daytime sleepiness during the trial between pitolisant- and placebo-treated participants.[6] To measure the daytime sleepiness, the investigators used a scale called the Epworth Sleepiness Scale (ESS).[6] 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).[6] Participants rate each item from zero (would never doze) to three (high chance of dozing).[6]

Pitolisant was approved by the U.S. Food and Drug Administration (FDA) in August 2019.[6] It was granted orphan drug designation for the treatment of narcolepsy,[9] 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.[10]

References[]

  1. ^ a b c d "Wakix- pitolisant hydrochloride tablet, film coated". DailyMed. 6 November 2019. Retrieved 18 August 2020.
  2. ^ a b c d e f g "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.
  3. ^ a b "Ozawade EPAR". European Medicines Agency (EMA). Retrieved 15 October 2021.
  4. ^ "FDA Approves Pitolisant for Daytime Sleepiness in Patients with Narcolepsy". Pharmacy Times. Retrieved 18 August 2020.
  5. ^ 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.
  6. ^ a b c d e f g h i j k l m "Drug Trials Snapshots: Wakix". U.S. Food and Drug Administration (FDA). 14 August 2019. Retrieved 18 March 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ^ "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.
  8. ^ a b 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.
  9. ^ "Pitolisant Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 17 May 2010. Retrieved 25 May 2021.
  10. ^ "Harmony's pitolisant granted breakthrough and fast track designations". Pharma Business International. 22 May 2018. Retrieved 25 May 2021.

External links[]

  • "Pitolisant". Drug Information Portal. U.S. National Library of Medicine.
  • "Ciproxidine". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT01067222 for "Efficacy and Safety Study of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy (Harmony1)" at ClinicalTrials.gov
  • Clinical trial number NCT01638403 for "Effects of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy." at ClinicalTrials.gov


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