Histamine H3 receptor inverse agonist Pregnancy: Available case reports from clinical trials and post-marketing use have not determined a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, administration during organogenesis caused maternal and embryofetal toxicity in rats and rabbits, and administration during pregnancy and lactation in rats produced developmental delay and increased major malformations at high multiples of the maximum recommended human dose. A pregnancy exposure registry is available (US labelling section 8.1).

Pitolisant

Brand names: Wakix, Ozawade

Pitolisant is an oral histamine H3-receptor antagonist/inverse agonist used to treat excessive daytime sleepiness and cataplexy in adults with narcolepsy.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Recommended dosage range 17.8 mg to 35.6 mg once daily, reached by titration: week 1 — 8.9 mg once daily; week 2 — 17.8 mg once daily; week 3 — may increase to the maximum recommended dosage of 35.6 mg once daily

Route: Oral (tablets)

Frequency: Once daily in the morning upon wakening

Max: 35.6 mg once daily (17.8 mg once daily in CYP2D6 poor metabolisers, in moderate hepatic impairment, and in renal impairment with eGFR less than 60 mL/min/1.73 m2)

No UK SPC (eMC) record was returned for this drug — the dose above is taken from US labelling (WAKIX, Harmony Biosciences, label date 2026-02-13) and MUST be checked against the current UK SPC, including how the strength is expressed, before clinical use. Indication in the source: excessive daytime sleepiness (EDS) or cataplexy in narcolepsy. Consider genotyping for CYP2D6 metaboliser status before initiation to determine the maximum dose. Dose may be adjusted for tolerability; it may take up to 8 weeks for some patients to achieve a clinical response. If a dose is missed, take the next dose the following day in the morning upon wakening. Moderate hepatic impairment (Child-Pugh class B), adults: start 8.9 mg once daily and increase after 14 days to a maximum of 17.8 mg once daily; contraindicated in severe hepatic impairment. Paediatric dosing (6 years and older) in the source is by weight band, not per kg: week 1 — 4.45 mg once daily; week 2 — 8.9 mg once daily; week 3 — 17.8 mg once daily, which is the maximum for patients weighing under 40 kg; week 4 — for patients weighing 40 kg or more, may increase to a maximum of 35.6 mg once daily. Verify all paediatric dosing against a children's formulary.

Dose adjustments

Renal

eGFR less than 60 mL/min/1.73 m2, adults: start 8.9 mg once daily and increase after 7 days to a maximum of 17.8 mg once daily. End-stage renal disease: not recommended (US labelling section 2.5).

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Known hypersensitivity to pitolisant or any component of the formulation (anaphylaxis has been reported)
Severe hepatic impairment

Side effects

Insomnia (most common in adults, at least 5% and at least twice placebo)
Nausea (adults)
Anxiety (adults)
Headache (most common in paediatric patients 6 years and older, together with insomnia)
QT interval prolongation — monitor QTc in patients with hepatic or renal impairment

Interactions

Strong CYP2D6 inhibitors — increase pitolisant exposure 2.2-fold; reduce the maximum recommended dose by half
Strong CYP3A4 inducers — decrease pitolisant exposure by approximately 50%; assess for loss of efficacy and, for patients stable on 8.9 mg or 17.8 mg once daily, increase to double the original daily dose (to 17.8 mg or 35.6 mg respectively) over 7 days
Sensitive CYP3A4 substrates, including hormonal contraceptives — pitolisant may reduce their effectiveness; use an alternative non-hormonal contraceptive method during treatment and for at least 21 days after discontinuation
Drugs that prolong the QT interval — avoid concomitant use; also avoid in patients with known QT prolongation, a history of cardiac arrhythmia, symptomatic bradycardia, hypokalaemia, hypomagnesaemia or congenital long QT

Clinical monograph

How it works

By blocking presynaptic H3 autoreceptors it increases the synthesis and release of histamine and other wake-promoting neurotransmitters in the brain, enhancing wakefulness.

Prescribing in practice

It can prolong the QT interval, so caution and ECG consideration are needed with cardiac disease, electrolyte disturbance, or other QT-prolonging drugs.
It is taken once daily in the morning and titrated upward, with dose adjustment required in hepatic and renal impairment.
It may reduce the effectiveness of hormonal contraceptives, so an alternative method should be used during and for some weeks after treatment.

Monitoring

Monitor for QT prolongation where risk factors exist, along with insomnia, anxiety, headache and gastrointestinal effects.

Counselling the patient

Take it once a day in the morning to avoid disturbing your sleep.
Use a reliable non-hormonal contraceptive method, as it can stop the pill working.
Report palpitations, fainting, or persistent anxiety to your team.

Evidence & guidelines

The HARMONY trials demonstrated reductions in daytime sleepiness and cataplexy, and NICE recommends it as an option for narcolepsy with or without cataplexy.

Reference: NICE TA665/TA766; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale · Neuromuscular

Pathways