Version July 2025
Note: Dosage form considerations: Dosing below is based on pitolisant base. In the United States, tablet strengths are listed as 4.45 mg and 17.8 mg (pitolisant base); whereas, international products may be listed as 4.5 mg and 18 mg (approximate pitolisant base amount), and Canadian products are listed as 5 mg and 20 mg (pitolisant hydrochloride).
Narcolepsy (excessive daytime sleepiness/cataplexy): Oral: Initial: 8.9 mg once daily in the morning for 1 week, then increase to 17.8 mg once daily for 1 week; may further increase dose based on response and tolerability during week 3 to a maximum dose of 35.6 mg once daily.
Dosage adjustment for known CYP2D6 poor metabolizers: Oral: Initial (treatment-naive): 8.9 mg once daily; may further increase dose based on response and tolerability after 1 week to a maximum dose of 17.8 mg once daily.
Obstructive sleep apnea–related excessive daytime sleepiness (off-label use):
Oral: Initial: 4.45 mg once daily in the morning for 1 week, may then increase to 8.9 mg once daily for 1 week based on response and tolerability; may further increase based on response and tolerability during week 3 to a maximum of 17.8 mg once daily (Ref).
Dosage adjustment for known CYP2D6 poor metabolizers: Maximum dose: 8.9 mg once daily (Ref).
Missed dose: If morning dose is missed, administer the next dose the following morning upon awakening.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Narcolepsy:
eGFR ≥60 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling.
eGFR 15 to <60 mL/minute/1.73 m2: Oral: Initial: 8.9 mg once daily for 1 week, then increase to a maximum dose of 17.8 mg once daily.
eGFR <15 mL/minute/1.73 m2 (end-stage renal disease): Use is not recommended.
Obstructive sleep apnea–related excessive daytime sleepiness (off-label use):
eGFR ≥90 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).
eGFR 15 to 89 mL/minute/1.73 m2: Oral: Maximum dose: 8.9 mg once daily (Ref).
eGFR <15 mL/minute/1.73 m2 (end-stage renal disease): Use is not recommended (Ref).
Narcolepsy:
Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate hepatic impairment (Child-Pugh class B): Oral: Initial: 8.9 mg once daily for 2 weeks, then increase to a maximum dose of 17.8 mg once daily.
Severe hepatic impairment (Child-Pugh class C): Use is contraindicated; has not been studied.
Obstructive sleep apnea–related excessive daytime sleepiness (off-label use):
Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary (Ref).
Moderate hepatic impairment (Child-Pugh class B): Oral: Increase initial dosage after 2 weeks. Maximum dose: 8.9 mg once daily (Ref).
Severe hepatic impairment (Child-Pugh class C): Use is contraindicated; has not been studied (Ref).
Refer to adult dosing.
(For additional information see "Pitolisant: Pediatric drug information")
Dosage guidance:
Dosage form information: In the US, tablet strengths are listed as 4.45 mg and 17.8 mg (pitolisant base), whereas international products may be listed as 4.5 mg and 18 mg (approximate pitolisant base amount) and Canadian products are listed as 5 mg and 20 mg (pitolisant hydrochloride). Initial prescription (for titration) requires multiple strengths of tablets to achieve appropriate titration.
Narcolepsy (excessive daytime sleepiness):
Note: Dosing presented as pitolisant base. May require 8 weeks of treatment to fully assess efficacy.
Children ≥6 years and Adolescents:
Patient weight <40 kg: Titrate up over 3 weeks to achieve recommended dose based on tolerability.
Week 1: Oral: 4.45 mg (one 4.45 mg tablet) once daily in the morning for 7 days.
Week 2: Oral: 8.9 mg (two 4.45 mg tablets) once daily for 7 days.
Week 3 and thereafter: Oral: May increase to 17.8 mg (one 17.8 mg tablet) once daily in the morning; maximum daily dose: 17.8 mg/day.
Patient weight ≥40 kg: Titrate up over 4 weeks to achieve recommended dose based on tolerability.
Week 1: Oral: 4.45 mg (one 4.45 mg tablet) once daily in the morning for 7 days.
Week 2: Oral: 8.9 mg (two 4.45 mg tablets) once daily in the morning for 7 days.
Week 3: Oral: May increase to 17.8 mg (one 17.8 mg tablet) once daily in the morning for 7 days.
Week 4 and thereafter: Oral: May increase to 35.6 mg (two 17.8 mg tablets) once daily in the morning; maximum daily dose: 35.6 mg/day.
CYP2D6 poor metabolizers: Note: Dosing presented as pitolisant base.
Children ≥6 years and Adolescents:
Patient weight <40 kg: Titrate up over 2 weeks to achieve recommended dose based on tolerability.
Week 1: Oral: 4.45 mg (one 4.45 mg tablet) once daily in the morning for 7 days.
Week 2 and thereafter: Oral: 8.9 mg (two 4.45 mg tablets) once daily in the morning; maximum daily dose: 8.9 mg/day.
Patient weight ≥40 kg: Titrate up over 3 weeks to achieve recommended dose based on tolerability.
Week 1: Oral: 4.45 mg (one 4.45 mg tablet) once daily in the morning for 7 days.
Week 2: Oral: 8.9 mg (two 4.45 mg tablets) once daily in the morning for 7 days.
Week 3 and thereafter: Oral: May increase to 17.8 mg (one 17.8 mg tablet) once daily in the morning; maximum daily dose: 17.8 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Calculate eGFR using the Schwartz equation.
Children ≥6 years and Adolescents:
eGFR ≥60 mL/minute/1.73 m2: Oral: No dosage adjustment necessary.
eGFR 15 to <60 mL/minute/1.73 m2: Note: Monitor closely for QT prolongation.
Patient weight <40 kg: Oral: Initiate as usual for first 2 weeks; maximum daily dose: 8.9 mg/day.
Patient weight ≥40 kg: Oral: Initiate as usual for first 3 weeks; maximum daily dose: 17.8 mg/day.
eGFR <15 mL/minute/1.73 m2 (end-stage renal disease): Use is not recommended.
Children ≥6 years and Adolescents:
Mild liver impairment: Oral: No dosage adjustment necessary.
Moderate liver impairment: Note: Pitolisant is extensively metabolized by the liver and exposure is significantly increased; monitor closely for QT prolongation. Slower titration necessary.
Patient weight <40 kg:
Weeks 1 and 2: Oral: 4.45 mg (one 4.45 mg tablet) once daily in the morning for 14 days.
Week 3 and thereafter: Oral: 8.9 mg (two 4.45 mg tablets) once daily in the morning; maximum daily dose: 8.9 mg/day.
Patient weight ≥40 kg:
Weeks 1 and 2: Oral: 4.45 mg (one 4.45 mg tablet) once daily in the morning for 14 days.
Weeks 3 and 4: Oral: 8.9 mg (two 4.45 mg tablets) once daily in the morning for 14 days.
Week 5 and thereafter: Oral: May increase to 17.8 mg (one 17.8 mg tablet) once daily in the morning; maximum daily dose: 17.8 mg/day.
Severe liver impairment: Use is contraindicated.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults, unless otherwise noted.
>10%: Nervous system: Headache (children, adolescents, adults: 18% to 19%; including migraine)
1% to 10%:
Cardiovascular: Increased heart rate (3%; including tachycardia)
Dermatologic: Skin rash (2%)
Gastrointestinal: Abdominal pain (3%), decreased appetite (3%), nausea (6%), xerostomia (2%)
Nervous system: Anxiety (5%), cataplexy (2%), hallucination (3%), insomnia (children, adolescents, adults: 6% to 7%), irritability (3%), sleep disturbance (3%; including sleep paralysis, sleep talking)
Neuromuscular & skeletal: Musculoskeletal pain (5%)
Respiratory: Upper respiratory tract infection (5%)
Frequency not defined: Cardiovascular: Prolonged QT interval on ECG
Postmarketing:
Dermatologic: Pruritus
Endocrine & metabolic: Weight gain
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis)
Nervous system: Abnormal dreams, behavioral changes, bipolar mood disorder, depressed mood, depression, dizziness, fatigue, lack of emotion (anhedonia), nightmares, seizure, suicidal ideation, suicidal tendencies
Hypersensitivity to pitolisant or any component of the formulation; severe hepatic impairment.
Canadian labeling: Additional contraindications (not in the US labeling): Breastfeeding.
Concerns related to adverse effects:
• Cardiovascular: May prolong the QT interval; avoid use in patients with known QT prolongation or concomitant use with other agents known to prolong the QT interval. Risk may be greater in patients with hepatic or renal impairment. Avoid use in patients with a known history of cardiac arrhythmias or circumstances that may increase the risk of torsades de pointes or sudden death (eg, symptomatic bradycardia, hypokalemia, hypomagnesemia, congenital prolongation of the QT interval).
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require dose adjustment. Use is contraindicated in severe hepatic impairment (Child-Pugh class C).
• Renal impairment: Use with caution in patients with renal impairment; dose adjustment required. Use is not recommended in patients with end-stage renal disease (eGFR <15 mL/minute/1.73 m2).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Wakix: 4.45 mg, 17.8 mg
No
Tablets (Wakix Oral)
4.45 mg (per each): $166.73
17.8 mg (per each): $333.45
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Wakix: 5 mg, 20 mg
Oral: Administer once daily upon awakening. The Canadian product monograph recommends administration with food and not to chew, crush, or divide the tablets.
Oral: Administer in the morning upon awakening.
Canadian dosage form: Administer with food; swallow tablets whole; do not chew, divide, or crush.
Missed dose: If morning dose missed, do not administer later in the day; administer the next dose the following morning upon awakening.
Narcolepsy: Treatment of cataplexy or excessive daytime sleepiness in adults (US and Canadian labeling) and pediatric patients ≥6 years of age and weighing ≥30 kg (Canadian labeling) with narcolepsy; treatment of excessive daytime sleepiness in pediatric patients ≥6 years of age (US labeling) with narcolepsy.
Obstructive sleep apnea–related excessive daytime sleepiness
Pitolisant may be confused with Pitocin
Wakix may be confused with Lasix
Pitolisant may be confused with Pitogin brand name for oxytocin [Indonesia].
Wakix: Brand name for pitolisant [US] may be confused with Walix brand name for oxaprozin [Italy] or Warix brand name for podofilox [Switzerland].
Substrate of CYP2D6 (Major), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Antihistamines: May decrease therapeutic effects of Pitolisant. Risk X: Avoid
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
CYP2D6 Inhibitors (Moderate): May increase serum concentration of Pitolisant. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of Pitolisant. Management: Reduce the pitolisant dose by 50% if a strong CYP2D6 inhibitor is initiated. For patients already receiving strong CYP2D6 inhibitors, initial doses of pitolisant should be reduced and depends on age and patient weight. See full monograph for details. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Pitolisant. Management: If on a stable pitolisant dose of 8.9 mg or 17.8 mg/day and starting a strong CYP3A4 inducer, double the pitolisant dose over 7 days (ie, to either 17.8 mg/day or 35.6 mg/day, respectively). Reduce pitolisant dose by 50% when the inducer is discontinued. Risk D: Consider Therapy Modification
CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers): Pitolisant may decrease serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inducers). Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Hormonal Contraceptives: Pitolisant may decrease serum concentration of Hormonal Contraceptives. Management: Patients using hormonal contraception should be advised to use an alternative non-hormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuation of pitolisant treatment. Risk D: Consider Therapy Modification
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Mirtazapine: May decrease therapeutic effects of Pitolisant. Risk X: Avoid
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Promethazine: May decrease therapeutic effects of Pitolisant. Risk X: Avoid
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Tricyclic Antidepressants: May decrease therapeutic effects of Pitolisant. Risk X: Avoid
Pitolisant may reduce the effectiveness of hormonal contraceptives. Patients who could become pregnant should be advised to use an alternative nonhormonal contraceptive method during treatment and for ≥21 days after the last dose of pitolisant.
Adverse events were observed in some animal reproduction studies. Outcome data following maternal use of pitolisant during pregnancy are limited.
Treatments other than pitolisant are currently recommended for pregnant patients with obstructive sleep apnea (Dominguez 2023); data are not available to make specific recommendations for the treatment of narcolepsy (AASM [Maski 2021]).
Data collection to monitor pregnancy and infant outcomes following exposure to pitolisant is ongoing. Patients exposed to pitolisant during pregnancy are encouraged to enroll in the Wakix Pregnancy Registry (https://wakixpregnancyregistry.com; 800-302-2813 or 800-833-7460).
Pitolisant is present in breast milk.
Data related to the presence of pitolisant in breast milk are available from 8 lactating patients, 11 to 96 weeks postpartum. Breast milk was sampled 24 hours following a single dose of pitolisant 35.6 mg. The mean maximum breast milk concentration was 47.5 ng/mL with 50% measurable within the first 4 hours following the maternal dose. Based on this single-dose data, product labeling estimates the infant dose of pitolisant via breast milk to be 0.009 mg/kg/day or 0.564% of the maternal dose.
According to the manufacturer, due to the potential for effects to the infant, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Renal and hepatic function (at baseline and as clinically indicated)
The mechanism of action of pitolisant is unclear, but may be mediated through its activity as an antagonist/inverse agonist at histamine-3 receptors.
Onset: In the treatment of narcolepsy, it may take up to 8 weeks for patients to achieve a clinical response; in the treatment of obstructive sleep apnea–associated excessive daytime sleepiness, up to 12 weeks may be required for patients to achieve a clinical response.
Absorption: ~90%
Distribution: Vd: 700 L (5 to 10 L/kg)
Protein binding: 91% to 96%
Metabolism: Metabolized by CYP2D6 and to a lesser extent by CYP3A4 to inactive metabolites
Half-life elimination: ~20 hours (7.5 to 24.2 hours)
Time to peak: Tmax: 3.5 hours (2 to 5 hours)
Excretion: Urine: ~90% (<2% as unchanged drug); feces: 2.3%
Pediatric: Compared to adults, exposure is higher in children: Cmax in children 7 to 11 years was 3.4-fold higher than adults and children ≥12 years and adolescents was 2.2-fold higher; AUC in children 7 to 11 years was 3.6-fold higher than adults and children ≥12 years and adolescents was 2-fold higher following a single dose.
Other:
The AUC in CYP2D6 poor metabolizers is 2.4 times higher than in normal metabolizers.
Molecular weight: 332.31.
