Pitolisant Dosing for Narcolepsy
For adults with narcolepsy, initiate pitolisant at 8.9 mg once daily upon wakening in week 1, increase to 17.8 mg in week 2, and may increase to the maximum dose of 35.6 mg once daily in week 3 based on individual response and tolerability. 1
Standard Adult Dosing Algorithm
The FDA-approved titration schedule follows a structured weekly escalation 1:
- Week 1: Start with 8.9 mg once daily in the morning upon wakening
- Week 2: Increase to 17.8 mg once daily
- Week 3: May increase to maximum recommended dose of 35.6 mg once daily
Administer as a single morning dose upon wakening to optimize efficacy and minimize insomnia risk. 1
Pediatric Dosing (≥6 Years for Excessive Daytime Sleepiness)
For children 6 years and older, use a more gradual titration 1:
- Week 1: 4.45 mg once daily
- Week 2: 8.9 mg once daily
- Week 3: 17.8 mg once daily (maximum for patients <40 kg)
- Week 4: For patients ≥40 kg, may increase to 35.6 mg once daily
Dose Adjustments for Special Populations
Moderate Hepatic Impairment (Child-Pugh Class B)
Adults: Start at 8.9 mg once daily, maximum 17.8 mg after 14 days 1
Pediatric patients: Start at 4.45 mg once daily, increase to 8.9 mg after 14 days; for patients ≥40 kg, may increase to 17.8 mg after another 14 days 1
Severe hepatic impairment is a contraindication to pitolisant use. 1
Renal Impairment (eGFR <60 mL/min/1.73 m²)
Adults: Start at 8.9 mg once daily, maximum 17.8 mg after 7 days 1
Pediatric patients: Start at 4.45 mg once daily, increase to 8.9 mg after 7 days; for patients ≥40 kg, may increase to 17.8 mg after another 7 days 1
Pitolisant is not recommended in end-stage renal disease. 1
Poor CYP2D6 Metabolizers
Adults: Maximum dose is 17.8 mg once daily 1
Pediatric patients: Maximum is 8.9 mg once daily for patients <40 kg and 17.8 mg for patients ≥40 kg 1
Concomitant Strong CYP2D6 Inhibitors
When used with strong CYP2D6 inhibitors, the maximum recommended dose is 17.8 mg once daily regardless of patient weight 1
Clinical Response Timeline
Clinical response typically begins within 2-3 weeks of treatment initiation. 2 In the HARMONY trials, statistical separation from placebo for excessive daytime sleepiness occurred at week 2-3, with cataplexy improvement evident by week 2-5 2. Treatment responders (ESS reduction ≥3) were significantly more common with pitolisant versus placebo beginning at week 3 2.
Important Safety Considerations
Pitolisant causes QT interval prolongation—avoid use with other QT-prolonging drugs and in patients with risk factors for prolonged QT. 1 Monitor patients with hepatic or renal impairment for increased QTc 1.
Pitolisant reduces the effectiveness of hormonal contraceptives through CYP3A4 induction. 1 Use alternative non-hormonal contraceptive methods during treatment and for at least 21 days after discontinuation 1.
Based on animal data, pitolisant may cause fetal harm, though human data are insufficient. 3, 1 The balance of risks and harms differs for pregnant and breastfeeding women 3.
Common Adverse Effects
The most frequently reported adverse reactions include headache, insomnia, weight gain, and nausea 3, 4. In clinical trials, these adverse events did not result in treatment cessation 3. The American Academy of Sleep Medicine determined that benefits outweigh risks with moderate-quality evidence from 3 RCTs 3.
Clinical Efficacy Evidence
Pitolisant demonstrates robust efficacy with Cohen's d effect sizes of 0.61-0.86 for excessive daytime sleepiness and 0.86 for cataplexy, with numbers needed to treat of 3-5 for sleepiness and 3-4 for cataplexy 5. The American Academy of Sleep Medicine issues a STRONG recommendation for pitolisant use in adults with narcolepsy 3, 6.
Pitolisant is the only anti-narcoleptic drug not scheduled as a controlled substance in the USA, with minimal abuse potential demonstrated in preclinical and clinical studies. 4