From the Guidelines
Pitolisant is a recommended treatment for excessive daytime sleepiness in adults with narcolepsy, as it has been shown to improve wakefulness and quality of life with a favorable balance of benefits and risks, as supported by the American Academy of Sleep Medicine clinical practice guideline 1. The benefits of pitolisant include improved wakefulness during the day without the stimulant effects of other wake-promoting medications, as it works through a different mechanism by targeting histamine receptors in the brain. It can help reduce sleep attacks, improve alertness, and enhance quality of life for patients with these sleep disorders. Some key points to consider when prescribing pitolisant include:
- Common side effects include insomnia, headache, nausea, anxiety, and irritability, as reported in studies evaluating its efficacy and safety 1.
- More serious risks include psychiatric symptoms like depression, hallucinations, and abnormal thoughts, as well as potential heart rhythm changes in susceptible individuals.
- Pitolisant may also interact with other medications, particularly those metabolized by certain liver enzymes.
- The typical starting dose is 8.9 mg once daily in the morning, potentially increasing to a maximum of 35.6 mg daily based on response and tolerability.
- Patients should be monitored for side effects, especially during dose adjustments, and those with liver or kidney problems may require dose modifications.
- Pitolisant should be avoided during pregnancy and breastfeeding due to limited safety data, as noted in the clinical practice guideline 1. Overall, the decision to prescribe pitolisant should be based on a careful evaluation of the potential benefits and risks for each individual patient, taking into account their specific medical history and circumstances.
From the FDA Drug Label
The following adverse reactions are discussed in more detail in other sections of the labeling: QT Interval Prolongation [see Warnings and Precautions (5.1)]
- 1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice
Adult Patients with Narcolepsy In clinical trials for narcolepsy, 172 adult patients were treated with WAKIX in placebo-controlled trials for up to 8 weeks and in open-label extension trials for up to 5 years. In trials in which WAKIX was directly compared to placebo, 6 of the 152 patients (3.9%) who received WAKIX and 4 of the 114 patients (3. 5%) who received placebo discontinued because of an adverse reaction. Most Common Adverse Reactions In the placebo-controlled clinical trials conducted in patients with narcolepsy with or without cataplexy, the most common adverse reactions (occurring in ≥5% of patients and at least twice the rate of placebo) with the use of WAKIX were insomnia (6%), nausea (6%), and anxiety (5%)
- 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of WAKIX
The risks of pitolisant include:
- QT interval prolongation
- Insomnia
- Nausea
- Anxiety
- Upper respiratory tract infection
- Musculoskeletal pain
- Heart rate increased
- Hallucinations
- Irritability
- Abdominal pain
- Sleep disturbance
- Decreased appetite
- Cataplexy
- Dry mouth
- Rash
The benefits of pitolisant are not explicitly stated in the provided drug labels, but it is indicated for the treatment of narcolepsy.
From the Research
Risks of Pitolisant
- The most common treatment-emergent adverse events included headache, insomnia, and anxiety, consistent with its mechanism of action 3, 4, 5
- Severe adverse events were rare, with one reported case of abdominal discomfort with pitolisant and five cases with modafinil, including abdominal pain, abnormal behavior, and amphetamine-like withdrawal symptoms 4
- The risk ratio of treatment-emergent adverse events (TEAEs) was 1.37, with insomnia being the only TEAE significantly associated with pitolisant treatment 6
Benefits of Pitolisant
- Pitolisant was demonstrated to have minimal risk of abuse in preclinical and clinical studies, and is the only anti-narcoleptic drug not scheduled as a controlled substance in the USA 3
- Pitolisant administered at up to the recommended maximum dose of 36 mg once daily reduces excessive daytime sleepiness (EDS) and cataplexy in adults with narcolepsy relative to placebo 3, 4, 5
- Pitolisant showed significant improvements in EDS, mean sleep latency, and quality of life compared to placebo in patients with narcolepsy and obstructive sleep apnea (OSA) 6
- Pitolisant offers the convenience of oral, once-daily administration, extending the range of approved treatment options available to adult patients with narcolepsy with or without cataplexy 3, 5