Orzeyful (oveporexton)

A tablet taken twice each morning for adults with narcolepsy type 1 (narcolepsy with cataplexy). The FDA approved it on August 5, 2026 and described it as the first medicine to directly target the loss of orexin signaling behind the disease. It cannot be sold until the Drug Enforcement Administration (DEA) finishes classifying it as a controlled substance; on September 29, 2026 Takeda's website still listed it as pending, with availability expected by November 2026.

Narcolepsy type 1 is caused by the loss of brain cells that make orexin (also called hypocretin), a chemical messenger that regulates wakefulness, sleep and muscle tone. Without orexin, people have overwhelming daytime sleepiness, cataplexy (sudden muscle weakness triggered by strong emotions such as laughter) and disrupted nighttime sleep^[3]. Oveporexton activates orexin receptor 2, one of the receptors orexin normally switches on, which stands in for the missing signal^[1]. According to Takeda, this promotes wakefulness and reduces REM sleep-like events such as cataplexy^[4].

Orzeyful has no boxed warning. It must not be taken with strong CYP3A inhibitors such as itraconazole, which raised oveporexton levels about 7-fold. In 2 pooled 12-week trials, the most common side effects for the 2 mg dose, the 1 mg dose and placebo were insomnia (60%, 55% and 1%), frequent urination (58%, 53% and 5%), urgent need to urinate (16%, 15% and 1%) and extra saliva (7%, 8% and 0%). About 90% of insomnia cases began in the first 2 days and about 63% cleared within a week; if insomnia lasts more than 7 days and affects daily life, the dose can be lowered or stopped. Creatine phosphokinase (CPK), a muscle enzyme, rose above 5 times normal without symptoms in 11% of patients on Orzeyful against 5% on placebo, so unexplained muscle pain, weakness or dark urine should be reported. LDL cholesterol above 160 mg/dL was seen in 32% against 20%, and blood pressure and heart rate rose more on the first day of treatment. Side effects led 2.6% of patients to stop, against 1.3% on placebo. The label also notes a potential for abuse: in a study of people with recreational stimulant experience, drug liking was higher than placebo and similar to or lower than phentermine^[1].

Either 1 mg or 2 mg by mouth after waking, then the same dose again 3 to 5 hours later, with or without food, at about the same times each day. The maximum is 4 mg a day. Tablets (0.5 mg, 1 mg and 2 mg) are swallowed whole with water, not split, crushed or chewed. People taking a moderate CYP3A inhibitor such as fluconazole take 0.5 mg twice (1 mg a day), and strong or moderate CYP3A inducers should be avoided. A missed dose is skipped, never doubled. It should be avoided with severe liver impairment or kidney failure on dialysis^[1]. Takeda plans to supply it through a specialty pharmacy once DEA scheduling is complete^[4].

Yes, Oveporexton (Orzeyful) is FDA approved (2026) for the treatment of Narcolepsy Type 1.

The FDA approved Orzeyful on August 5, 2026, but it cannot be sold until the Drug Enforcement Administration (DEA) publishes its decision on how the drug will be scheduled as a controlled substance. Takeda said that decision was expected within 90 days of approval, and on September 29, 2026 its website listed expected availability by November 2026, through a specialty pharmacy.

Orzeyful activates orexin receptor 2, standing in for orexin, the wake-promoting brain chemical that people with narcolepsy type 1 have lost. The FDA said no earlier narcolepsy medicine acted on the orexin system. Its trials compared it with placebo, so they do not show how it compares with modafinil, oxybates, pitolisant or stimulants.

In the 2 main trials, the most common side effects on the 2 mg dose were insomnia (60% against 1% on placebo), frequent urination (58% against 5%), urgent need to urinate (16% against 1%) and extra saliva (7% against 0%). Most insomnia started in the first 2 days and about 63% of cases cleared within a week. Only 2.6% of patients stopped because of side effects.

The label dose is either 1 mg or 2 mg after waking and the same dose again 3 to 5 hours later, with or without food, up to 4 mg a day. Tablets are swallowed whole with water. People on a moderate CYP3A inhibitor such as fluconazole take 0.5 mg twice, and strong CYP3A inhibitors are not allowed.