pitolisant

Adjunctive therapy

Brands: Wakix

Last reviewed 2025-12-30

Reviewed by PsychMed Editorial Team.

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Quick answers

What is pitolisant?
Pitolisant (brand Wakix) is a wake-promoting medication indicated for excessive daytime sleepiness (EDS) and cataplexy in adult patients with narcolepsy (label).
What is Wakix?
Wakix is a brand name for pitolisant.
What is Wakix (pitolisant) used for?
Label indications include: Treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy (label).
What drug class is Wakix (pitolisant)?
Histamine H3 receptor inverse agonist/antagonist (pitolisant) indicated for excessive daytime sleepiness and cataplexy in narcolepsy; non-scheduled but has clinically important QT prolongation risk at higher exposures and dose adjustments for CYP2D6 status and interacting medications.
What strengths does Wakix (pitolisant) come in?
Tablets: 4.45 mg and 17.8 mg (label).

Snapshot

Class: Adjunctive therapy
Common US brands: Wakix
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-30

Label indications

Treatment of excessive daytime sleepiness or cataplexy in adult patients with narcolepsy (label).

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Clinical Highlights

Pitolisant (brand Wakix) is a wake-promoting medication indicated for excessive daytime sleepiness (EDS) and cataplexy in adult patients with narcolepsy (label). It is a histamine H3 receptor inverse agonist/antagonist and is not a controlled substance, which can be a meaningful practical distinction versus stimulant-class options in some settings (label/clinical).

QT prolongation risk is clinically central: higher exposures (CYP2D6 poor metabolizers, strong CYP2D6 inhibitors, hepatic impairment, and certain drug combinations) increase risk, so interaction review and dose limits are key safeguards (label).
Pitolisant can reduce effectiveness of hormonal contraceptives (CYP3A4 induction); non-hormonal contraception is recommended during therapy and for 21 days after discontinuation (label).
The compare view, pitolisant evidence feed, and pitolisant print page help compare non-stimulant wake-promoting strategies and monitoring considerations.

Dosing & Formulations

Tablets: 4.45 mg and 17.8 mg (label). Adults: titrate weekly—8.9 mg once daily in the morning (week 1), 17.8 mg once daily (week 2), and may increase to 35.6 mg once daily (week 3) based on response and tolerability (label).

Dose adjustments apply for known CYP2D6 poor metabolizers and for strong CYP2D6 inhibitors; maximum recommended dosage is 17.8 mg once daily in those settings (label).
Morning dosing is emphasized; late-day dosing increases insomnia risk and can worsen circadian disruption (label/clinical).

Monitoring & Risks

QT prolongation is the key safety risk; avoiding other QT-prolonging agents when possible and accounting for interaction-driven exposure increases is a common practical strategy (label/clinical). In patients with cardiovascular disease or complex polypharmacy, ECG review and a focused QT risk assessment (including electrolytes and co-medications) is often considered before dose escalation (clinical).

Insomnia, anxiety, and irritability can occur; monitoring is important in serious mental illness, particularly in bipolar-spectrum illness (clinical).
Hepatic impairment can increase exposure; pitolisant is contraindicated in severe hepatic impairment and requires dose modification in moderate hepatic impairment (label).

Drug Interactions

Strong CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, bupropion) can increase exposure; reduce dose and cap at 17.8 mg once daily (label). Strong CYP3A4 inducers reduce exposure and may reduce efficacy; dosing adjustments may be needed with careful follow-up (label/clinical).

Pitolisant may reduce effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives; use non-hormonal contraception during therapy and for 21 days after discontinuation (label).

Practice Notes

Wake-promoting treatment selection often balances EDS severity, cataplexy burden, psychiatric comorbidity, interaction load, and feasibility of monitoring (clinical). Because pitolisant is not scheduled, it may be preferred when misuse risk is a dominant constraint, but QT-focused risk management is a required trade-off (label/clinical).

When insomnia worsens, emphasis often shifts to dose timing, sleep opportunity, and circadian alignment before adding additional activating medications (clinical).

References

WAKIX (pitolisant) tablets prescribing information — DailyMed (2025)
Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline — Journal of Clinical Sleep Medicine (2021)
Treatment OF Central Disorders OF Hypersomnolence: AN American Academy OF Sleep Medicine Systematic Review, Meta Analysis, AND Grade Assessment — Journal of Clinical Sleep Medicine (2021)
Pitolisant versus placebo or modafinil in patients with narcolepsy — Lancet Neurology (2013)