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pitolisant

Adjunctive therapy

Brand: Wakix

Published 2025-12-23 · Last reviewed 2025-12-30 · 4 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: 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).·Half-life: Single-dose mean 20 h·LAI available: No

Class: Adjunctive therapy
Typical dose: 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).
Half-life: Single-dose mean 20 h
LAI available: No

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)?: H3 Inverse Agonist.
What is the mechanism of action of 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).

General information

Pitolisant (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. Medication selection often balances misuse risk, psychiatric comorbidity, and monitoring feasibility (label/clinical).

QT prolongation risk is clinically central; higher exposures (CYP2D6 poor metabolizers, strong CYP2D6 inhibitors, hepatic impairment, and interacting regimens) increase risk, so dose limits and interaction review are key safeguards (label).

Pitolisant may reduce effectiveness of hormonal contraceptives (CYP3A4 induction); non-hormonal contraception is recommended during therapy and for 21 days after discontinuation (label).

The pitolisant compare view, evidence feed, and print page support review of non-stimulant strategies and monitoring considerations.

U.S. approvals

Excessive daytime sleepiness in narcolepsy (adults) (2019)
Cataplexy in narcolepsy (adults) (2019)

Formulations & strengths

Tablets: 4.45 mg and 17.8 mg (label).

Generic availability

Not available generically (brand-only).

Pitolisant offers a non-scheduled wake-promoting option for narcolepsy, but QT-focused safety management (dose limits, interaction review, and attention to hepatic impairment and CYP2D6 status) is a required trade-off and commonly shapes patient selection (label/clinical).

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Pitolisant is a histamine H3 receptor inverse agonist/antagonist, increasing histaminergic signaling in the brain and promoting wakefulness (label/clinical).

Compared with stimulant reuptake inhibitors, pitolisant is often framed as a non-scheduled option, but insomnia and anxiety can still occur and require monitoring, particularly in serious mental illness (clinical).

Histamine H3 receptor inverse agonism/antagonism (wake-promoting mechanism).

Metabolism & pharmacokinetics

Pitolisant is primarily metabolized by CYP2D6 and to a lesser extent by CYP3A4; metabolites are not pharmacologically active (label).
After a single dose, median half-life is ~20 hours (range ~7.5–24.2 hours). Renal clearance accounts for <2% of total clearance (label).
CYP2D6 poor metabolizers and strong CYP2D6 inhibitors increase exposure; dose adjustments and maximum dosage limits are required to reduce QT risk (label).

Dosing & administration

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).
Morning dosing is emphasized; late-day dosing increases insomnia risk (label/clinical).
Strong CYP2D6 inhibitors or known CYP2D6 poor metabolizers: maximum recommended dosage is 17.8 mg once daily (label).
Hepatic impairment requires careful selection; pitolisant is contraindicated in severe hepatic impairment and requires dosage modification in moderate hepatic impairment (label).

Monitoring & labs

QT risk review (history, co-medications, exposure-increasing interactions) (label/clinical).
Mood and psychiatric symptom monitoring (anxiety, agitation, mania/psychosis) (clinical).
Sleep disruption monitoring (insomnia, circadian effects) (clinical).
Drug interaction review (CYP2D6 inhibitors; CYP3A4 inducers; contraception) (label).
Hepatic function status review for dosing safety (label).

Adverse effects

FDA boxed warnings

Common side effects (≥10%)

Insomnia: Common activating adverse effect; morning dosing is emphasized (label/clinical).
Headache: Common and often transient (label/clinical).
Nausea: Can occur; assess meal timing and hydration (clinical).
Anxiety / irritability: May worsen baseline anxiety; monitor in serious mental illness (clinical).

Other notable effects

QT prolongation risk increases with higher exposure; avoid exceeding maximum recommended dosages and account for CYP2D6 status and interacting medications (label).
Contraceptive effectiveness may be reduced for hormonal methods; counsel use of non-hormonal contraception during therapy and for 21 days after discontinuation (label).

Interactions

Strong CYP2D6 inhibitors increase exposure (about 2.2-fold); reduce dose and cap at 17.8 mg once daily (label).
Strong CYP3A4 inducers decrease exposure (about 50%); assess for loss of efficacy and adjust dosing per label (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).
Avoidance of other QT-prolonging agents when possible is a common risk management strategy, especially in polypharmacy (label/clinical).

Other useful information

Evidence syntheses and guidelines support wake-promoting agents for excessive daytime sleepiness in central hypersomnolence disorders; choice is individualized based on symptom profile, comorbidity, and monitoring feasibility (AASM/clinical).
In serious mental illness, clinicians often monitor closely for insomnia, anxiety, and mood destabilization when adding wake-promoting agents, and prioritize nonpharmacologic contributors to sleepiness when present (clinical).

References

Related hubs:SMI toolkit·Support resources