On August 14, 2019, the U.S. Food and Drug Administration (FDA) approved WAKIX (pitolisant) for the treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy. The approved recommended dosage of WAKIX is 17.8 mg to 35.6 mg administered orally once daily in the morning upon wakening. Titrate dosage as follows:
If a dose is missed, patients should take the next dose the following day in the morning upon wakening.
It may take up to 8 weeks for some patients to achieve a clinical response.
WAKIX is contraindicated in patients with severe (Child Pugh C) hepatic impairment. Additionally, there is also a significant increase in pitolisant exposure in patients with moderate (Child Pugh B) hepatic impairment. WAKIX prolongs the QT interval. Avoid use of WAKIX in patients with known QT prolongation or with a history of cardiac arrhythmias, as well as other circumstances that may increase the risk of the occurrence of torsade de pointes or sudden death. The risk of QT prolongation may be greater in patients with hepatic or renal impairment. Monitor patients with hepatic or renal impairment for increased QTc.
Additional information regarding dosage and administration and warnings and precautions can be found in the full prescribing information linked below.
Mechanism of Action (MOA), Pharmacokinetics (PK), and Pharmacodynamics (PD)
Use in Specific Populations
Additional information regarding use in specific populations can be found in the full prescribing information linked below.
Efficacy and Safety
Efficacy of WAKIX for the treatment of EDS in adult patients with narcolepsy was evaluated in two multicenter, randomized, double-blind, placebo-controlled studies. Patients ≥ 18 years of age who met the International Classification of Sleep Disorders (ICSD-2) criteria for narcolepsy and who had an Epworth Sleepiness Scale (ESS) score ≥ 14 were eligible to enroll in the studies. EDS was assessed using the ESS, an 8-item questionnaire by which patients rate their perceived likelihood of falling asleep during usual daily life activities. The primary endpoint for both studies was the least square mean final ESS score compared to placebo. Additional information regarding efficacy trials can be found in the full prescribing information linked below.
The most common adverse reactions (≥ 5% and twice placebo) for WAKIX were insomnia, nausea, and anxiety.
Full prescribing information is available at https://go.usa.gov/xVawA.
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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.