How Does Xywav Work For Idiopathic Hypersomnia? Plus, Pharmacists Answer 4 More FAQs

Idiopathic hypersomnia (IH) is a rare sleep disorder that causes extreme sleepiness during the day, even after you’ve gotten a full night’s sleep. People with IH may sleep 9 hours or more per night but still wake up feeling as if they haven’t slept at all. IH also causes sleep inertia, or “sleep drunkenness,” making it difficult to get out of bed. Even long naps often aren’t refreshing for people with IH. But with IH, there’s no clear reason for the sleepiness — that’s why it’s called “idiopathic.”

In August 2021, the FDA approved Xywav as a treatment option for IH. In fact, it’s the only medication that’s FDA-approved for this condition. Here, we’ll discuss how Xywav works for IH, how it compares to other IH medications, and more.

1. How does Xywav work for IH?

Xywav is an oral liquid solution containing a mixture of four active ingredients. They’re each a form of oxybate salt:

• Calcium oxybate

• Magnesium oxybate

• Potassium oxybate

• Sodium oxybate

The active molecule in Xywav is oxybate, a central nervous system depressant. This means it slows your brain function. More specifically, oxybate is related to a chemical messenger in the body called gamma-aminobutyric acid (GABA). GABA decreases nerve cell activity, so it has a calming effect on the brain and body. When you take medication containing oxybate, it boosts the effects of GABA.

It’s not completely understood how Xywav works to treat IH. But experts think that while you’re sleeping, greater GABA activity in certain parts of your brain promotes better quality sleep, so you wake up feeling more rested.

2. What else is Xywav used for?

Xywav was originally FDA-approved in 2002 to treat excessive daytime sleepiness (EDS) and cataplexy (sudden muscle weakness triggered by strong emotions) in people at least 7 years old who have narcolepsy. It became FDA-approved for IH in adults in 2021.

Xywav is unique because it’s the only medication that’s specifically FDA-approved for IH. Other medications, such as Provigil (modafinil), are also recommended for IH, but they’re used off-label. Off-label use is when a medication is prescribed for a condition for which it’s not FDA-approved.

3 . Is Xywav a controlled substance?

Yes. Xywav is a controlled substance. This means it has a risk for dependency and misuse. 

As mentioned above, the active ingredient in Xywav is oxybate — the salt form of a substance called gamma-hydroxybutyrate (GHB). GHB is an illegal drug that can calm the body and produce a “high.” GHB has the potential to cause dependency and be misused.

When Xywav is taken as prescribed, it’s considered safe. But since it’s related to GHB, it has risks, too, especially when used incorrectly. Some risks can be life-threatening, including slowed breathing, seizures, and coma. 

Serious risks are why Xywav can only be prescribed and dispensed under a Risk Evaluation and Mitigation Strategies (REMS) program. This means there are special requirements put in place by the federal government to monitor and control how Xywav is prescribed and used. For example, only certified healthcare professionals (HCPs) can prescribe Xywav. And only certified pharmacies can dispense it.

4. How does Xywav compare to other medications for IH?

The American Academy of Sleep Medicine (AASM) has guidelines for treating sleep disorders including IH. According to AASM, Provigil is the first-choice medication for treating IH. Provigil is recommended over other medications for most people because we have more research on its use in IH. But it’s important to note that the AASM guidelines were developed before Xywav was FDA-approved for IH. Larger, better designed studies of Xywav show it may improve more symptoms of IH than separate studies of Provigil found. Notably, people taking Xywav reported improvements in sleep inertia and daytime functioning.

However, other medications can also treat IH and may even be better options for some people. Other medications besides Xywav to treat IH include:

• Xyrem (sodium oxybate)

• Clarithromycin

• Ritalin (methylphenidate)

• Wakix (pitolisant)

Xywav versus Xyrem

You may notice that Xyrem contains sodium oxybate, just like Xywav does. We don’t have any studies comparing Xywav with Xyrem at this time. But because they both contain the same active molecule oxybate, they’re expected to work just as well for IH. There are differences, though. The major differences between these two medications are:

• Xywav contains 92% less sodium than Xyrem at approved doses. While they both contain the same amount of oxybate, Xywav contains a mixture of oxybate salts, instead of just sodium. So Xywav may be preferred in people with conditions where consuming too much sodium can be problematic, such as heart failure, high blood pressure, and kidney problems.

• Only Xywav is FDA-approved for IH. But Xyrem may still be used off-label for this condition.

5. Is Xywav safe?

When taken under the care of a medical professional trained to prescribe Xywav, it’s considered safe for many people. However, like all medications, it has possible risks. Possible Xywav side effects may include:

• Nausea and vomiting

• Headache

• Increased sweating

• Decreased appetite

• Dizziness

• Parasomnia (such as sleepwalking)

• Tremor (shakiness)

• Trouble sleeping

• Dry mouth

• Diarrhea

• Anxiety

More serious risks are also possible, including:

• Dependence and misuse

• Slowed breathing, especially in people who take other medications or substances that slow brain function (such as alcohol, opioids, benzodiazepines, and other sleep medications)

• Excessive drowsiness, making it unsafe to drive or difficult to complete other daily tasks

• Sleep apnea, as well as other sleep-related breathing problems, which can be especially likely in people who already have apnea

• Sleep-related behaviors, such as sleepwalking, which may cause injuries 

• Mental health side effects, including hallucinations, depression, and suicidal thoughts (The risk is greater if you have existing depression, or a history of depression and suicidal thoughts or actions.) 

Avoid driving or operating machinery for at least 6 hours after taking Xywav. But when you first start taking Xywav, it’s a good idea to be even more cautious until you know how it affects you. And if you experience excessive drowsiness, sleepwalking, or changes in your mood while taking Xywav, contact your HCP immediately.

If you or someone you know is having thoughts of suicide, you’re not alone, and help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.

Good to know: Xywax can interact with other medications. For example, Xywav shouldn’t be used with other sleep medications, because the combination increases your risk of slowed breathing. Examples include zolpidem (Ambien) and eszopiclone (Lunesta), among others. Before starting Xywav, give your HCP and pharmacist a list of all the medications and over-the-counter products you take. This will help them check for interactions.

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Written by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Daphne Berryhill, RPh

Daphne Berryhill, RPh, has two decades of experience as a clinical pharmacist. She spent most of her career in the Chicago area practicing in-home infusion.

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