Pitolisant: Recently FDA Approved for Narcolepsy


Michael J. Thorpy, MD: In the last year or so, we’ve had 2 new medications approved for the treatment of narcolepsy. Russ, would you like to discuss this? There’s one called pitolisant. Tell us about that.

Russell Rosenberg, PhD, DABSM: That’s probably the most recent FDA [Food and Drug Administration]-approved drug for improving alertness or wakefulness during the daytime. It’s only indicated for narcolepsy. The modafinils, as you know, are approved for other disorders of sleepiness. But Wakix, or pitolisant, is the one that, most recently, was shown to be effective for excessive daytime sleepiness associated with narcolepsy. A couple different clinical trials are worth discussing, just briefly. They used the Epworth Sleepiness Scale and found that during the course of the initial trials—an 8-week period—the scores improved. In Europe, the drug is approved for both improving wakefulness and treating cataplexy. In this country, the FDA has not yet approved it for the treatment of cataplexy. It does seem to have some positive impact on reducing cataplexy, and I do know of some sleep specialists who are using it off label for that particular purpose.

It’s nice because this is the only wakefulness drug that is nonscheduled, so it’s easier for physicians to prescribe and may be easier to get multiple prescriptions or enough that the patient doesn’t have to come back every month to get a new prescription. But it’s not without its potential adverse effects and issues that physicians need to be cautious about. Similar to the modafinils, it can reduce the efficacy of oral contraceptives. But it’s certainly a nice new tool for physicians to have in their toolbox for treating narcolepsy.

Michael J. Thorpy, MD: There were 2 major studies done with pitolisant: 1 for cataplexy and 1 for excessive sleepiness. These studies were done in Europe, and they were shown to be effective in treating both cataplexy and sleepiness. But in the United States, it was only approved by the FDA for sleepiness. Do you think that when using it to treat those type 1 narcolepsy patients who have both cataplexy and sleepiness that it will have some beneficial effect on the cataplexy?

Russell Rosenberg, PhD, DABSM: I do think it will have some beneficial effect in those patients who have cataplexy. I should also mention that this is a once-a-day dosing. There’s no need to give a second dose. We participated in an early access program for this drug and found that it seemed to carry most patients through the late afternoon, in terms of keeping them alert and awake. It didn’t run out of steam by lunchtime. It just kept going. One of the adverse effects of any potential wake-promoting drug is causing insomnia in patients. We did see a little bit of that, but I don’t think that’s unique to pitolisant. I think you have to be careful and make sure patients are taking the dose right when they wake up in the morning, especially if they’re having any difficulty falling asleep at night.

Michael J. Thorpy, MD: It has quite a novel mechanism of action, doesn’t it? Do you want to discuss that?

Russell Rosenberg, PhD, DABSM: We know the usual suspects—dopamine, norepinephrine, acetylcholine, and serotonin. But 1 neurotransmitter that has not been previously implicated in excessive sleepiness has been histamine, although I think we all know that the antihistamines do cause sleepiness. So anything that improves or increases the amount of available histamine can have a positive impact. That’s this drug. This is the only drug that does actually have an impact on increasing histamine in the brain—therefore causing wakefulness. There may be others coming down the line after pitolisant, but this is currently the only drug to address that mechanism of action.

Michael J. Thorpy, MD: Can you use this drug in children, Kiran?

Kiran Maski, MD, MPH: There’s a clinical trial in Europe, so hopefully we too will have another tool in our toolbox. I see patients aged 25 and younger. I also was part of the early access program. I think this medication has a slightly lower adverse effect profile in terms of anxiety or mood disorders, so it’s been beneficial for patients who have those comorbidities where stimulants can really make those situations worse. This is a medication that seems to be a little bit more neutral in regard to mood comorbidities.

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