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From The Medical Letter on Drugs and Therapeutics
September 21, 2021

Pitolisant (Wakix) for Narcolepsy

JAMA. 2021;326(11):1060-1061. doi:10.1001/jama.2021.1349

The FDA has approved pitolisant (Wakix – Harmony), a histamine-3 (H3 )–receptor antagonist/inverse agonist, for treatment of excessive daytime sleepiness (EDS) or cataplexy in adults with narcolepsy. It is the first H3-receptor antagonist/inverse agonist to become available in the US and the first non-controlled substance to receive FDA approval for these indications. Pitolisant has been available in Europe since 2016.

The CNS stimulant modafinil (Provigil, and generics) and its R-enantiomer armodafinil (Nuvigil, and generics) have been used for years for first-line treatment of EDS due to narcolepsy. Alternative treatments include sympathomimetic stimulants such as mixed amphetamine salts (Adderall, and generics) and methylphenidate (Ritalin, and others). Solriamfetol (Sunosi), a dopamine and norepinephrine reuptake inhibitor, was approved by the FDA in 2019 for treatment of EDS due to narcolepsy or obstructive sleep apnea; it has not been compared to first-line treatments.1 A sodium oxybate oral solution (Xyrem) and a mixed-salt oxybate oral solution (Xywav) are FDA-approved for treatment of EDS due to narcolepsy,2 but they can cause serious CNS adverse effects, including respiratory depression.3

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