Common Side Effects of Wakix (Pitolisant)
Wakix (pitolisant) commonly causes headache, insomnia, nausea, anxiety, and weight gain as its primary side effects, with none typically resulting in treatment discontinuation. 1
Primary Side Effects
Based on placebo-controlled clinical trials in patients with narcolepsy, the most common adverse reactions (occurring in ≥5% of patients and at least twice the rate of placebo) with Wakix were:
- Headache (18% vs 15% with placebo)
- Insomnia (6% vs 2% with placebo)
- Nausea (6% vs 3% with placebo)
- Anxiety (5% vs 1% with placebo)
- Upper respiratory tract infection (5% vs 3% with placebo)
- Musculoskeletal pain (5% vs 3% with placebo) 2
Additional Side Effects
Other adverse reactions occurring at ≥2% and more frequently than placebo include:
- Heart rate increased (3% vs 0%)
- Hallucinations (3% vs 0%)
- Irritability (3% vs 2%)
- Abdominal pain (3% vs 1%)
- Sleep disturbance (3% vs 2%)
- Decreased appetite (3% vs 0%)
- Cataplexy (2% vs 1%)
- Dry mouth (2% vs 1%)
- Rash (2% vs 1%) 2
Serious Warnings and Precautions
QT Interval Prolongation
Wakix prolongs the QT interval and should be avoided in:
- Patients with known QT prolongation
- Combination with other QT-prolonging drugs
- Patients with cardiac arrhythmia history
- Circumstances that increase risk of torsade de pointes or sudden death:
- Symptomatic bradycardia
- Hypokalemia or hypomagnesemia
- Congenital QT prolongation 2
The risk may be greater in patients with hepatic or renal impairment due to higher pitolisant concentrations. These patients should be monitored for increased QTc. 2
Postmarketing Experience
Additional adverse reactions identified during post-approval use include:
- Fatigue
- Hypersensitivity reactions (including anaphylaxis)
- Weight increased
- Dizziness, epilepsy
- Psychiatric disorders: abnormal behavior, abnormal dreams, anhedonia, bipolar disorder, depression, depressed mood, nightmare, sleep disorder, suicide attempt, suicidal ideation
- Pruritus 2
Advantages Over Other Narcolepsy Medications
Wakix is the only wake-promoting medication not scheduled as a controlled substance by the DEA, which may be beneficial for certain patient populations. 3, 4 It works through histaminergic pathways rather than adrenergic pathways, potentially making it less likely to lower seizure threshold. 3
Monitoring Recommendations
Patients taking Wakix should be monitored for:
- QT interval prolongation, especially with hepatic or renal impairment
- Improvement in sleepiness scores
- Psychiatric symptoms
- Sleep quality and vivid dreams 3, 2
Dosing Considerations
Dosage modification is recommended in patients with moderate hepatic impairment and moderate or severe renal impairment. Wakix is contraindicated in patients with severe hepatic impairment and not recommended in patients with end-stage renal disease. 2
Pitolisant may reduce the effectiveness of hormonal contraceptives, so alternative non-hormonal contraceptive methods should be used during treatment and for at least 21 days after discontinuation. 2