Pitolisant

The mechanism of action of pitolisant in excessive daytime sleepiness (EDS) or cataplexy in patients 6 years and older with narcolepsy is unclear. However, its efficacy could be mediated through its activity as an antagonist/inverse agonist at histamine-3 (H3) receptors.

• WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients 6 years of age and older with narcolepsy.ICD-10: G47.419

• WAKIX is contraindicated in patients with: known hypersensitivity to pitolisant or any component of the formulation. Anaphylaxis has been reported in patients treated with WAKIX [see Adverse Reactions ( 6.2 )] .contraindicated

See Full Prescribing Information for complete dosage instructions ( 2.2 , 2.3 ) Administer orally once daily in the morning upon wakening ( 2.2 , 2.3 ) Dosage Recommendations: Adults ( 2.2 ) Week 1 Initiate with a dosage of 8.9 mg once daily Week 2 Increase dosage to 17.8 mg once daily Week 3 May increase to the maximum recommended dosage of 35.6 mg once daily Pediatric Patients (6 years and older) ( 2.3 ) Week 1 Initiate with a dosage of 4.45 mg once daily Week 2 Increase dosage to 8.9 mg once daily Week 3 Increase dosage to 17.8 mg once daily, the maximum recommended dosage for patients weighing <40 kg Week 4 For patients weighing ≥40 kg, may increase to the maximum recommended dosage of 35.6 mg once daily Hepatic impairment ( 2.4 , 8.6 , 12.3 ): Moderate hepatic impairment (Child-Pugh Class B): Adults: Initial dosage is 8.9 mg once daily. Increase to a maximum dosage of 17.8 mg once daily after 14 days Pediatric Patients: Initial dosage is 4.45 mg once daily. Increase to 8.9 mg once daily after 14 days; for patients weighing ≥40 kg, may increase to 17.8 mg once daily after another 14 days Renal impairment (eGFR less than 60 mL/minute/1.73 m 2 ) ( 2.5 , 8.7 , 12.3 ): Adults: Initial dosage is 8.9 mg once daily.

QT Interval Prolongation : Increases in QT interval. Avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. Monitor patients with hepatic or renal impairment for increased QTc ( 5.1 ) 5.1 QT Interval Prolongation WAKIX prolongs the QT interval. The use of WAKIX should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval [see Drug Interactions ( 7.1 )]. WAKIX should also be avoided in patients with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and the presence of congenital prolongation of the QT interval [see Clinical Pharmacology ( 12.2 )]. The risk of QT prolongation may be greater in patients with higher concentrations of pitolisant (e.g., patients with hepatic or renal impairment). Monitor patients with hepatic or renal impairment for increased QTc. Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment [see Dosage and Administration ( 2.4 , 2.5 )] . WAKIX is contraindicated in patients with severe hepatic impairment [see Contraindications ( 4 )] . WAKIX is not recommended in patients with end-stage renal disease (ESRD) [see Dosage and Administration ( 2.5 ), Use in Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )] .

The following adverse reactions are discussed in more detail in other sections of the labeling: QT Interval Prolongation [see Warnings and Precautions ( 5.1 )] Most common adverse reactions (≥5% and at least twice placebo) in adults: insomnia, nausea, and anxiety ( 6.1 ). Most common adverse reactions (≥5% and greater than placebo) in pediatric patients 6 years and older: headache and insomnia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Harmony Biosciences at 1-800-833-7460 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult Patients with Narcolepsy In clinical trials for narcolepsy, 172 adult patients were treated with WAKIX in placebo-controlled trials for up to 8 weeks and in open-label extension trials for up to 5 years. In trials in which WAKIX was directly compared to placebo, 6 of the 152 patients (3.9%) who received WAKIX and 4 of the 114 patients (3.5%) who received placebo discontinued because of an adverse reaction. Most Common Adverse Reactions In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (occurring in ≥5% of patients and at least twice the rate of placebo) with the use of WAKIX were insomnia (6%), nausea (6%), and anxiety (5%).

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women who are exposed to WAKIX during pregnancy. Patients should be encouraged to enroll in the WAKIX pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call 1-800-833-7460. Risk Summary Available case reports from clinical trials and postmarketing reports with WAKIX use in pregnant women have not determined a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproductive studies, administration of pitolisant during organogenesis caused maternal and embryofetal toxicity in rats and rabbits at doses ≥13 and >4 times the maximum recommended human dose (MRHD) of 35.6 mg based on mg/m 2 body surface area, respectively. Oral administration of pitolisant to female rats during pregnancy and lactation adversely affected maternal and fetal health and produced developmental delay at doses ≥13 times the MRHD, based on mg/m 2 body surface area and increased the incidence of major malformations at 22 times the MRHD (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

Metabolism

Following oral administration of pitolisant 35.6 mg once daily, the steady state C max and AUC are 73 ng/mL (range: 49.2 to 126 ng/mL) and 812 ng*hr/mL (range: 518 to 1468 ng*hr/mL), respectively. Pitolisant exposure (C max and AUC) increases proportionally with dose and steady state is reached by day 7.

• Aug 14, 2019NDANDA211150Harmony

1. 1Drug Ineffective23111%
2. 2Nausea22911%
3. 3Anxiety22311%
4. 4Headache21411%
5. 5Insomnia21411%
6. 6Product Administration Interrupted1999.9%
7. 7Somnolence1808.9%
8. 8Fatigue1738.6%
9. 9Product Dose Omission Issue1718.5%
10. 10Middle Insomnia1185.8%
11. 11Dizziness1175.8%
12. 12Depression1105.5%
13. 13Surgery1075.3%
14. 14Feeling Abnormal964.8%
15. 15Vomiting894.4%

The 10 most recently updated of 36 ClinicalTrials.gov registrations naming Pitolisant as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• WAKIX® (Pitolisant) Pregnancy Registry
  Recruiting · Observational · 1,329 enrolled · Harmony Biosciences Management, Inc.
  NCT05536011updated 2026-06-12
• A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension
  Completed · Phase 2 · Interventional · 65 enrolled · Harmony Biosciences Management, Inc.
  NCT04257929updated 2026-05-12
• A Phase 3 Efficacy and Safety Study of HBS-301 in Participants With Idiopathic Hypersomnia (IH)
  Recruiting · Phase 3 · Interventional · 248 enrolled · Harmony Biosciences Management, Inc.
  NCT07500090updated 2026-03-30
• A Study of Pitolisant in Patients With Prader-Willi Syndrome
  Recruiting · Phase 3 · Interventional · 134 enrolled · Harmony Biosciences Management, Inc.
  NCT06366464updated 2026-03-17
• A Study of Pitolisant in Participants With Prader-Willi Syndrome
  Enrolling by invitation · Phase 3 · Interventional · 150 enrolled · Harmony Biosciences Management, Inc.
  NCT07219485updated 2026-03-17
• A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients With Idiopathic Hypersomnia
  Completed · Phase 3 · Interventional · 119 enrolled · Harmony Biosciences Management, Inc.
  NCT05458128updated 2025-12-12
• A Study of HBS-201 (Pitolisant Delayed-release)
  Completed · Phase 1 · Interventional · 46 enrolled · Harmony Biosciences Management, Inc.
  NCT07051252updated 2025-12-12
• Proof of Concept Study on Pitolisant Effect on Autism Spectrum Disorders in Children and Adolescents
  Active not recruiting · Phase 2 · Interventional · 62 enrolled · Bioprojet
  NCT05953389updated 2025-10-02
• Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period
  Completed · Phase 3 · Interventional · 110 enrolled · Bioprojet
  NCT02611687updated 2025-06-26
• Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1
  Completed · Phase 2 · Interventional · 30 enrolled · Harmony Biosciences Management, Inc.
  NCT04886518updated 2025-04-25

CPIC-curated drug–gene pairs for Pitolisant. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2D6CPIC A (provisional)FDA label: Actionable PGx

Frequently asked questions

How does Pitolisant work?

The mechanism of action of pitolisant in excessive daytime sleepiness (EDS) or cataplexy in patients 6 years and older with narcolepsy is unclear. However, its efficacy could be mediated through its activity as an antagonist/inverse agonist at histamine-3 (H3) receptors.

What is Pitolisant used for?

According to FDA labeling, Pitolisant carries indications including: WAKIX is indicated for the treatment of excessive daytime sleepiness (EDS) or cataplexy in patients 6 years of age and older with narcolepsy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Pitolisant?

Pitolisant is classified as Other nervous system drugs, Histamine-3 Receptor Antagonist/Inverse Agonist, Cytochrome P450 3A4 Inducers, Histamine H3 Receptor Antagonists, Histamine H3 Receptor Inverse Agonists, Decreased Central Nervous System Histamine Activity.

What are the brand names for Pitolisant?

Pitolisant is marketed under brand names including Wakix.

What are the contraindications for Pitolisant?

Pitolisant labeling lists contraindications including: WAKIX is contraindicated in patients with: known hypersensitivity to pitolisant or any component of the formulation. Anaphylaxis has been reported in patients treated with WAKIX [see Adverse Reactions ( 6.2 )] .. Always consult the full prescribing information and a clinician.