FDA Expands Use of Pitolisant for Pediatric Patients With Narcolepsy With Cataplexy

The FDA expanded the clinical utility of pitolisant (Wakix) by approving it for the treatment of cataplexy in patients 6 years of age and older with narcolepsy. This regulatory milestone establishes pitolisant as the first and only nonscheduled treatment option for both pediatric and adult narcolepsy patients, regardless of whether they experience cataplexy.¹

“Wakix is now the first-and-only FDA-approved treatment option for both pediatric and adult narcolepsy patients with or without cataplexy that is not scheduled as a controlled substance, an important distinction that supports its clinical utility,” Jeffrey M. Dayno, MD, president and CEO of Harmony Biosciences, said in a news release.¹

Although it was previously approved for excessive daytime sleepiness in adults in 2019 and pediatrics in 2024, this new indication allows physicians and pharmacists to address the sudden and brief muscle weakness triggered by emotions that characterizes narcolepsy type 1 in younger populations.¹

For pharmacists, the nonscheduled status of pitolisant is a significant distinction from other narcolepsy treatments, such as sodium oxybate or psychostimulants, which are typically controlled substances. This status is attributed to its unique mechanism as a selective histamine 3 receptor antagonist and inverse agonist. By blocking these receptors, pitolisant increases the synthesis and release of histamine, a vital wake-promoting neurotransmitter, without increasing dopamine levels in the brain's reward centers, thereby avoiding the potential for abuse or typical withdrawal symptoms upon discontinuation.^1,2

Recent real-world data from a 5-year European post-authorization safety study (PASS) provides pharmacists with extensive evidence regarding the long-term safety and utilization patterns of pitolisant. The interim analysis, which followed 370 patients for a median of over 42 months, confirmed that the drug is generally safe and well-tolerated in patients with both narcolepsy type 1 and type 2. Pharmacists should note that 68.4% of the study population had at least 1 comorbidity, with high rates of obesity and cardiovascular disease, making the drug's safety profile particularly relevant for complex patients.²

The PASS data also highlighted a significant improvement in patient-reported outcomes beyond the primary symptoms of sleepiness and cataplexy. There was a notable reduction in depressive symptoms, with the proportion of patients reporting moderate-to-severe depression decreasing from 41.5% at the start of the study to 22.5% after 3 years. Patients also reported an enhanced quality of life, specifically regarding their ability to perform daily activities and a reduction in anxiety and pain.²

Another finding for clinical pharmacy is that cardiovascular parameters, including blood pressure and heart rate, remained stable throughout the study period. This suggests that pitolisant may be a preferable option for narcoleptic patients who are at a higher risk for cardiovascular issues. Although weight gain is a common concern in narcolepsy management, the PASS found that weight remained stable for the vast majority of patients over 3 years of treatment, and some obese patients even experienced weight loss.²

Pharmacists play a vital role in managing the complex drug-drug interactions associated with pitolisant. Because it is a borderline/weak inducer of CYP3A4, the drug can reduce the effectiveness of hormonal contraceptives. Pharmacists must advise patients to use alternative nonhormonal contraceptive methods during treatment and for at least 21 days after stopping the medication. Furthermore, the dose of pitolisant must be reduced by half when used with strong CYP2D6 inhibitors, and adjustments are necessary for patients with moderate hepatic or renal impairment.^1,3

Adherence monitoring is another area where pharmacists can impact patient success. The PASS study observed that patient adherence was high and actually improved over time, reaching 90.2% by the third year. This high level of satisfaction and adherence may be linked to the drug's efficacy; the mean Epworth Sleepiness Scale scores, which measure daytime sleepiness, dropped significantly from a baseline of 15.3 to 10.5 after 3 years of therapy.²

Finally, pharmacists must be aware of the specific titration and administration requirements for pediatric patients. Dosing for children 6 years and older is determined by weight, with a maximum recommended dose of 35.6 mg for those weighing 40 kg or more and 17.8 mg for those weighing less. Pitolisant should be taken as a whole tablet immediately upon waking in the morning to mimic natural histamine cycles and minimize potential sleep disturbances like insomnia, which was reported as a common adverse reaction in both adult and pediatric clinical trials.^1,3

“We are excited to achieve this important milestone for pediatric narcolepsy patients who experience cataplexy,” Kumar Budur, MD, MS, chief medical and scientific officer of Harmony Biosciences, said in the news release.¹ “With this approval, clinicians now have the option to prescribe Wakix to treat excessive daytime sleepiness, cataplexy, or both, in patients 6 years and older with narcolepsy.”

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REFERENCES

1. Harmony Biosciences receives US Food and Drug Administration approval for Wakix (pitolisant) for the treatment of cataplexy in pediatric narcolepsy. News release. February 17, 2026. Accessed February 17, 2026. https://www.businesswire.com/news/home/20260217839280/en/Harmony-Biosciences-Receives-U.S.-Food-and-Drug-Administration-Approval-for-WAKIX-pitolisant-for-the-Treatment-of-Cataplexy-in-Pediatric-Narcolepsy

2. Plazzi G, Mayer G, Bodenschatz R, et al. Interim analysis of a post-authorization safety study of pitolisant in treating narcolepsy: A real-world European study. Sleep Med. 2025;129:20-30. doi:10.1016/j.sleep.2025.02.012

3. Mayo Clinic. Pitolisant (oral route). February 1, 2026. Accessed February 17, 2026. https://www.mayoclinic.org/drugs-supplements/pitolisant-oral-route/description/drg-20471214