What to Know About Wakix (Pitolisant)

Wakix (pitolisant) is a prescription medication that works to reduce excessive daytime sleepiness for the treatment of narcolepsy. It is a pill and its mechanism of action is through activity to increase histamine, a neurotransmitter that promotes wakefulness in the brain. What are the uses, potential side effects, available dosages, and recommended safety precautions related to this drug? Learn more about the use of Wakix and whether it might be the right treatment for you.

Uses

Wakix (pitolisant) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness in adults with narcolepsy. As a pill, it is taken once daily in the morning to improve wakefulness.

Although the exact mechanism of action is unknown, it is believed to bind to histamine-3 (H3) receptors as an antagonist and inverse agonist, leading to increased histamine levels within the brain.

It is not a stimulant medication and is therefore not restricted as a scheduled medication by the FDA.

Before Taking

It is important to be diagnosed with narcolepsy and this generally requires evaluation by a board-certified sleep medicine physician and testing that may include two parts:

• In-center diagnostic polysomnogram (PSG)
• Multiple sleep latency testing (MSLT)

Other causes of sleepiness must be excluded, including obtaining inadequate sleep to meet sleep needs, circadian disorders (such as delayed sleep phase syndrome or shift work), and other hypersomnias.

The degree of sleepiness may be further assessed, rarely objectively with the maintenance of wakefulness test (MWT), but more commonly with the subjective Epworth sleepiness scale.

Precautions and Contraindications

If you have had a prior allergic reaction to the drug, it should be avoided. It cannot be taken by patients with severe liver impairment and this may require testing to determine.

Discuss your medical conditions with your prescribing healthcare provider, including:

• Poor liver function
• Recent heart attack (myocardial infarction)
• Heart arrhythmias including bradycardia, QT prolongation, or torsades de pointes
• Congestive heart failure
• Electrolyte abnormalities (low potassium or magnesium)
• Poor kidney function (eGFR less than 15)
• Pregnancy (or planned pregnancy)
• Breastfeeding (or planned breastfeeding)

It may interact with other medications (including paroxetine, quinidine, and thioridazine), and you should review your complete medication list with your prescribing healthcare provider.

Other Stimulants

As a new medication, insurance may require the trial and failure of other prescription medications to improve sleepiness prior to approving the use of Wakix. These may include stimulant medications such as:

• Provigil (modafinil)
• Nuvigil (armodafinil)
• Concerta or Ritalin (methylphenidate)
• Adderall (dextroamphetamine/amphetamine)
• Vyvanse (lisdexamfetamine)

In addition to these stimulants, Xyrem (sodium oxybate) is used to improve sleepiness and cataplexy in narcolepsy.

Another medication called Sunosi (solriamfetol), which is a wake-promoting agent, can also be used in adults with narcolepsy.

Dosage

All listed dosages are according to the drug manufacturer. Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

Dosage in Narcolepsy

According to the manufacturer, Wakix is started at 8.9 milligrams (mg) once daily in adults with persistent sleepiness due to narcolepsy. The recommended dosage range is 17.8 mg to 35.6 mg once daily. Based on the response to treatment, the dose may be doubled every seven days as needed. The maximum recommended dosage is 35.6 mg once daily. Higher doses do not confer increased benefits to outweigh adverse reactions. 

It has not been approved by the FDA for use in children. This would be considered an off-label use.

Modifications

The doses are reduced in the setting of impairment of the function of the liver or kidneys. This depends on the severity, with a maximum dose of 17.8 mg in poor CYP2D6 metabolizers and those with Child-Pugh Class B. The dosing may be reduced in moderate to severe renal impairment. In severe liver impairment (Child-Pugh Class C) and end-stage kidney disease, Wakix is not recommended for use.

How to Take and Store

Wakix is taken by mouth upon awakening with or without food. It should not be taken later in the day due to the risk of it causing insomnia. If a dose is missed, excessive daytime sleepiness may occur, and you may have to wait until the next day to take your regularly scheduled dose.

It should be stored at 68 to 77 degrees Fahrenheit (or 20 to 25 degrees Celsius).

Side Effects

As with any medication, there are potential side effects that may occur with the use of Wakix (pitolisant). Some side effects may occur more commonly, and others may be severe but rare.

Common

Some of the common side effects associated with the use of Wakix (pitolisant) include:

• Insomnia (difficulty sleeping)
• Nausea
• Anxiety
• Headache
• Upper respiratory tract infection
• Musculoskeletal pain
• Increased heart rate
• Hallucinations
• Irritability
• Abdominal pain
• Decreased appetite
• Cataplexy
• Dry mouth
• Rash

If these occur, discuss with your prescribing healthcare provider whether the medication should be continued.

It may reduce the effectiveness of hormonal contraceptives and an alternative non-hormonal contraceptive method (i.e., condoms) may be required during treatment and for at least 21 days after discontinuing its use to prevent pregnancy.

Severe

The effects of Wakix (pitolisant) on the heart rhythm may lead to serious cardiovascular consequences if left unchecked, such as:

• Heart attack
• Heart failure
• Stroke
• Death

To avoid these potential events, your healthcare provider may need to check your baseline electrocardiogram (EKG) and review your risks for QT interval prolongation before and during the use of Wakix.

Warnings and Interactions

As noted previously, do not take Wakix if you have a history of severe liver and kidney impairment or a history of QT interval prolongation. 

It should not be taken with centrally active H1 receptor antagonists, such as antihistamine medications like diphenhydramine (bound in Benadryl and "PM" sleep aids), as this use will make it ineffective.

A Word From Verywell

Wakix appears to have modest effects on improving sleepiness and it may take up to eight weeks to note a benefit from the use of the medication, so it is advisable to discuss expectations with your sleep provider. For patients using the medication, the Wakix for You support program may be helpful. It may be useful to determine insurance coverage, offers financial support for eligible patients, coordinates with the specialty pharmacy to ship, and provides additional education resources.