Alcohol, Opioids, and More: 8 Xywav Interactions to Watch For

If you have narcolepsy or another condition of excessive daytime sleepiness, such as idiopathic hypersomnia (IH), you may be wondering about medications to manage your symptoms. A medication called Xywav is one option. It’s a liquid solution that contains four active ingredients that are all a form of oxybate.

Oxybate is a central nervous system (CNS) depressant. This means it slows your brain activity. It’s not fully understood how Xywav works. But it helps you sleep at night so that you feel more rested and awake during the day.

Like most medications, Xywav can have drug interactions. Typically, these interactions occur because these medications have similar side effects. Certain medications shouldn’t be taken with Xywav, while other combinations may require closer monitoring.

Xywav interactions at a glance

Xywav can interact with a variety of medications and substances that affect the brain and nervous system. These interactions can increase the risk of excessive sleepiness, slowed breathing, and overdose. Examples include:

• Benzodiazepines, such as alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan)

• Opioid medications, such as tramadol (ConZip, Qdolo) and Percocet (oxycodone / acetaminophen)

• Alcohol

• Prescription sleep medications, such as eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Intermezzo, Edluar)

• Over-the-counter (OTC) sleep aids, such as diphenhydramine (ZzzQuil) and doxylamine (Unisom)

• Muscle relaxers, such as cyclobenzaprine (Amrix), methocarbamol (Robaxin), and carisoprodol (Soma)

• Seizure medications, such as gabapentin (Neurontin), topiramate (Topamax), and levetiracetam (Keppra)

• Depakote (divalproex sodium) 

• Antidepressants, such as amitriptyline, escitalopram (Lexapro), and paroxetine (Paxil)

• Antipsychotic medications, such as quetiapine (Seroquel), olanzapine (Zyprexa), and clozapine (Clozaril)

The best way to manage Xywav interactions is to share an updated list of all prescription medications, OTC products, and substances you use with your healthcare team. Below, we take a closer look at eight important Xywav interactions.

1. Benzodiazepines

Like Xywav, benzodiazepines are CNS depressants that slow brain activity and can cause drowsiness, dizziness, and slowed breathing. Common benzodiazepines include alprazolam, clonazepam, and lorazepam.

Combining benzodiazepines with Xywave can intensify CNS depression and increase the risk of:

• Excessive sleepiness

• Dizziness and falls

• Fainting

• Slowed breathing

• Overdose

Benzodiazepines may also worsen daytime sleepiness, which can make narcolepsy or IH symptoms harder to manage. But if both medications are necessary, your prescriber may lower the dose of one or both medications and monitor you closely for side effects.

2. Opioids

Opioids are pain medications that cause sleepiness and slow your breathing. Since Xywav has similar effects, combining these medications can be dangerous. Examples of opioids include tramadol and oxycodone / acetaminophen.

Taking opioids with Xywav raises the risk of serious side effects, including:

• Extreme sedation

• Trouble breathing

• Low blood pressure

• Overdose

Opioids taken during the day can also worsen daytime drowsiness, which can worsen your narcolepsy or IH symptoms.

Before starting Xywav, tell your prescriber if you take opioid medications, even if you only take them occasionally. In some cases, they may recommend lowering your opioid dose, avoiding the combination, or pausing Xywav during short-term opioid treatment.

3. Alcohol

You shouldn’t drink alcohol if you take Xywav. Combining these substances can cause severe sedation, coordination problems, and trouble remembering events.

Before starting Xywav, have an honest conversation with your prescriber if you drink alcohol. If you feel you’re unable to stop drinking, tell them. They may talk to you about resources and medications that may help decrease how much you drink.

If you or someone you know struggles with substance use, help is available. Call the Substance Abuse and Mental Health Services Administration’s National Helpline at 1-800-662-4357 to learn about resources in your area.

4. Sleep medications

Many sleep medications can add to the sedating effects of Xywav. These include prescription “Z-drugs,” such as eszopiclone and zolpidem, and common OTC sleep aids, such as diphenhydramine and doxylamine.

Taking these medications with Xywav can cause excessive sleepiness, next-day drowsiness, and impaired coordination. This can increase the risk of falls, injuries, and trouble functioning during the day. It may also worsen narcolepsy or IH symptoms.

Z-drugs shouldn’t be combined with Xywav. And it’s best to avoid OTC sleep aids unless your healthcare team says it’s safe. Before starting Xywav, share a complete list of your prescription and OTC medications with your prescriber and pharmacist so they can screen for any interactions.

5. Muscle relaxers

Muscle relaxers are used to treat muscle spasms and pain. Many of these medications can cause sleepiness, dizziness, and trouble with coordination. Common muscle relaxers include cyclobenzaprine, methocarbamol, and carisoprodol.

Taking muscle relaxers with Xywav can increase the risk of:

• Excessive drowsiness

• Poor coordination

• Falls

• Slowed breathing

• Low blood pressure

• Overdose

If you’re prescribed a muscle relaxer while taking Xywav, tell your healthcare team right away. For short-term muscle relaxer treatment, they may recommend temporarily stopping Xywav or adjusting your medications to reduce safety risks.

6. Seizure medications, such as topiramate

Seizure medications often work by slowing brain activity, which can lead to dizziness and drowsiness. Examples include gabapentin, topiramate, and levetiracetam.

Not all seizure medications cause drowsiness. But for those that do, combining them with Xywav may increase the risk of excessive sedation, poor coordination, and daytime drowsiness.

Since seizure medications are often essential for preventing seizures, stopping them may not be an option. If you take one that causes drowsiness, your healthcare team can help weigh your risks and benefits of taking Xywav.

7. Depakote

Depakote is a seizure medication that’s also used to treat bipolar disorder and prevent migraines. It can interact with Xywav by increasing oxybate levels in the body, which can raise the risk of side effects. Depakote can also cause drowsiness on its own, which may be worse if you take it with Xywav.

Because of this interaction, your prescriber may recommend a lower Xywav dosage and monitor you more closely for side effects.

8. Some antidepressants and antipsychotics, such as Lexapro

Certain antidepressants and antipsychotic medications can cause drowsiness, dizziness, and slowed thinking. When these medications are combined with Xywav, the effects may become more intense. Examples of these medications include:

• Amitriptyline

• Escitalopram

• Paroxetine

• Quetiapine

• Olanzapine

• Clozapine

Taking these medications with Xywav may increase the risk of excessive sedation, poor coordination and falls, and daytime sleepiness.

Not all antidepressants and antipsychotics cause significant drowsiness. Before starting Xywav, ask your prescriber to review your medication list for possible interactions. They can determine whether dose adjustments, extra monitoring, or a different medication may be needed.

Frequently asked questions

Why trust our experts?

Written by:

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP

Nicole E. Cieri-Hutcherson, PharmD, BCPS, NCMP, has over a decade of experience as a pharmacist, professor, and researcher. She currently practices as a clinical pharmacist at Buffalo General Medical Center.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Our editorial standards

Meet our experts