First noncontrolled substance approved to treat narcolepsy in adults

Abstract

In August, FDA approved pitolisant (Wakix—Harmony Biosciences) for treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy. The selective histamine-3 receptor antagonist/inverse agonist is the first and only treatment for narcolepsy that is not scheduled as a controlled substance. “The approval of Wakix provides health care professionals managing people living with narcolepsy a new and important treatment option for their patients,” said Jeffrey Dayno, MD, Harmony Bioscience’s chief medical officer, in a statement. “Wakix … offers an important benefit/risk profile to address the unmet medical need that exists in people living with narcolepsy.” Pitolisant is available as both a 4.45-mg and 17.8-mg tablet and should be stored at 20°C to 25°C (68°F to 77°F). FDA’s approval was based on Harmony 1 and Harmony 1bis—two multicenter, double-blind, placebo-controlled studies. The studies randomized 261 patients to receive pitolisant, placebo, or active control. Participants were treated for 8 weeks, including a 3-week dose-titration phase followed by a 5-week stable-dose phase. In both studies, patients treated with pitolisant showed statistically significant improvement in EDS, as measured by the Epworth Sleepiness Scale. Common adverse effects of pitolisant include insomnia, nausea, and anxiety. The drug may also cause QT interval prolongation. Pitolisant may interact with a number of drugs. Its use with strong CYP2D6 inhibitors, for instance, increases the amount of pitolisant that patients are exposed to by 2.2-fold. The dose of pitolisant should be reduced by one-half, with a maximum dosage of 17.8 mg once daily, for patients who are concurrently using strong CYP2D6 inhibitors. Use of pitolisant with strong CYP3A4 inducers decreases the amount of pitolisant exposure in the blood by 50%. In patients taking CYP3A4 inducers, a dose adjustment should be considered, as detailed in pitolisant’s prescribing information. Pitolisant works by increasing the synthesis and release of histamine, so use of the drug with histamine-1 (H1) receptor antagonists that cross the blood–brain barrier may reduce its effectiveness. Patients taking pitolisant should avoid using centrally acting H1 receptor antagonists. Because pitolisant can prolong the QT interval, the drug should not be used in combination with other drugs that cause QT prolongation, as this can increase the risk of cardiac arrhythmia. Pitolisant may also reduce the effectiveness of sensitive CYP3A4 substrates, including hormonal contraceptives. Before they begin treatment with pitolisant, advise patients to inform their physician if they are taking, or planning to take, any prescription or OTC drugs. Counsel patients to consult their physician immediately if they feel faint, lose consciousness, or have heart palpitations, as these could be signs of prolongation of the QT interval. Pitolisant (Wakix)Manufacturer: Harmony BiosciencesDrug class: Histamine-3 (H3) receptor antagonist/inverse agonistIndication: Treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsyDosage: 17.8 mg to 35.6 mg once daily, taken orally in the morning upon awakening. Week 1: Start with 8.9 mg. Week 2: Increase dosage to 17.8 mg. Week 3: May increase to the maximum-recommended dosage of 35.6 mg. See prescribing information for more details.Of note: Pitolisant is contraindicated in patients with severe hepatic impairment (Child-Pugh C). The drug may increase the QT interval and could reduce the efficacy of hormonal contraceptives. Manufacturer: Harmony Biosciences Drug class: Histamine-3 (H3) receptor antagonist/inverse agonist Indication: Treatment of excessive daytime sleepiness (EDS) in adult patients with narcolepsy Dosage: 17.8 mg to 35.6 mg once daily, taken orally in the morning upon awakening. Week 1: Start with 8.9 mg. Week 2: Increase dosage to 17.8 mg. Week 3: May increase to the maximum-recommended dosage of 35.6 mg. See prescribing information for more details. Of note: Pitolisant is contraindicated in patients with severe hepatic impairment (Child-Pugh C). The drug may increase the QT interval and could reduce the efficacy of hormonal contraceptives. Pitolisant is metabolized extensively by the liver and is contraindicated in patients with severe hepatic impairment because the drug has not been studied in this population. Health care providers should monitor patients with moderate hepatic impairment, as these patients have shown increased amounts of the drug in their blood. Patients with mild hepatic impairment who are taking pitolisant should also be closely monitored. Emphasize to patients of reproductive potential that pitolisant may reduce the efficacy of hormonal contraceptives. Counsel these patients to use an alternative nonhormonal contraceptive method during treatment with pitolisant and for at least 21 days after discontinuing treatment. If a patient becomes pregnant during treatment with pitolisant, inform them that a pregnancy exposure registry is available to monitor pregnancy outcomes of the drug; patients can call 1-800-833-7460 to enroll or obtain information.