Grapefruit Juice, Antibiotics, and More: 8 Belsomra Interactions

If you’re living with insomnia, you may be taking (or thinking of starting) a sleeping medication. One option is Belsomra (suvorexant). It can help you fall asleep faster and stay asleep longer.

Belsomra interacts with many medications, food, and substances. Some interactions can cause or increase the risk of dangerous side effects, such as severe drowsiness. Others can make Belsomra less effective. So what interacts with Belsomra?

Belsomra interactions at a glance

Belsomra interacts with many medications. It also interacts with some foods and substances.

Common Belsomra interactions include:

• Other sleep medications, such as zolpidem (Ambien) and eszopiclone (Lunesta)

• Over-the-counter (OTC) sleep aids, such as doxylamine (Unisom SleepTabs)

• Sleep supplements, such as melatonin and valerian

• Opioid pain relievers, such as oxycodone (Roxicodone, OxyContin)

• Benzodiazepines, such as alprazolam (Xanax)

• Muscle relaxers, such as cyclobenzaprine (Amrix)

• Gabapentin (Neurontin, Horizant, Gralise)

• Trazodone

• Tricyclic antidepressants (TCAs), such as amitriptyline

• Older antihistamines, such as chlorpheniramine (Aller-Chlor)

• Alcohol

• Oral antifungal medications, such as ketoconazole and fluconazole (Diflucan)

• Grapefruit juice

• Medications that contain ritonavir (Norvir), such as Paxlovid (nirmatrelvir / ritonavir)

• Some HIV medications, such as nelfinavir (Viracept) and atazanavir (Reyataz)

• Certain antibiotics, such as clarithromycin (Biaxin XL) and ciprofloxacin (Cipro)

• St. John’s wort

• Some blood pressure medications, such as diltiazem (Cardizem) and verapamil (Verelan)

• Certain anti-seizure medications, such as carbamazepine (Tegretol) and phenytoin (Dilantin)

• Digoxin (Lanoxin)

This isn’t a full list of all possible Belsomra interactions. Share a medication list with your healthcare team so they can check for interactions. Below are details about eight Belsomra interactions and how you can manage them.

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1. Other sleep medications or supplements

You shouldn’t take Belsomra with other sleep medications. Combining multiple sleeping aids or supplements can lead to excessive drowsiness. It can also cause problems with coordination or balance.

Examples of sleeping medications that interact with Belsomra include:

• “Z-drugs,” such as zolpidem, eszopiclone, and zaleplon (Sonata)

• Benzodiazepines, such as triazolam (Halcion) and temazepam (Restoril)

• Other orexin receptor antagonists, such as lemborexant (Dayvigo) and daridorexant (Quviviq)

• Ramelteon (Rozerem)

• Doxepin (Silenor)

• OTC sleep aids, such as doxylamine and diphenhydramine (Benadryl, ZzzQuil)

• OTC sleep supplements, such as melatonin and valerian

Talk to your prescriber if Belsomra doesn’t seem to be helping. They can adjust your Belsomra dosage or switch you to a different medication.

2. Other medications that cause drowsiness

Sleep aids aren’t the only medications that make you sleepy. There are many other medications that cause drowsiness as a side effect. Combining them with Belsomra can make this side effect worse. And in some cases, the amount of drowsiness this interaction causes can be dangerous.

Other medications that cause drowsiness include:

• Opioids, such as oxycodone, hydrocodone, and tramadol (ConZip)

• Benzodiazepines, such as alprazolam and clonazepam (Klonopin)

• Muscle relaxers, such as cyclobenzaprine

• Gabapentin

• Trazodone

• TCAs, such as amitriptyline

• Older antihistamines, such as chlorpheniramine

EXPERT PICKS: WHAT TO READ NEXT

• All about side effects: Many Belsomra (suvorexant) interactions raise the risk of side effects.

• Getting the right dosage: Belsomra has a standard recommended dosage, but medication interactions can affect how much you should take.

• Is Belsomra a controlled substance? Read pharmacists’ answers to this and other frequently asked questions about Belsomra.

You may need to take Belsomra and another medication that causes drowsiness. In this case, ask your prescriber if you should separate them throughout the day. This may help manage this Belsomra interaction. If separating medications isn’t possible, your prescriber may lower your Belsomra dosage.

3. Alcohol

You should steer clear of alcohol if you’re taking Belsomra. The combination can cause severe impairment, including problems with coordination, balance, and alertness. This interaction can happen with any dose of Belsomra and any amount of alcohol.

To manage this Belsomra interaction, it’s best to avoid alcohol altogether. Alcohol generally stays in your bloodstream for about 6 hours after your last drink. But the sedative effects of Belsomra may last for days after your last dose. This means that Belsomra and alcohol can interact even if they’re not taken at or around the same time.

If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.

4. Oral antifungals, such as ketoconazole

Oral antifungals cause your body to break down Belsomra slower. This means that too much Belsomra stays in your system after your dose. This can make Belsomra side effects, such as drowsiness, more intense or more likely to happen.

Examples of oral antifungals that interact with Belsomra include:

• Ketoconazole

• Fluconazole

• Itraconazole (Sporanox)

You may need to take a lower Belsomra dose or stop it altogether. This depends on which antifungal you’re taking. Your healthcare team can tell you if you should make these changes.

Good to know: Antifungal creams don’t cause as many drug interactions as oral antifungals. This is because your body absorbs much less of these medications when applied to your skin.

5. Grapefruit juice

Grapefruit interacts with many medications, including Belsomra. Grapefruit slows the breakdown of Belsomra. This can raise Belsomra levels in your body and cause more side effects.

This Belsomra interaction can happen with any amount of grapefruit. But it’s more likely to occur with concentrated versions, such as grapefruit juice or extract.

If you drink grapefruit juice often or in large quantities, talk to your prescriber. They may give you the OK to combine them, but you’ll likely need a lower Belsomra dose. And you may need to cut back on how much grapefruit you consume.

6. Antiviral medications, such as Paxlovid

Antivirals treat infections caused by viruses. Not all antiviral medications interact with Belsomra. But some slow your body’s breakdown of the medication. This can raise the amount of Belsomra in your system, causing side effects.

Antivirals that interact with Belsomra include:

• Medications that contain ritonavir, such as Paxlovid

• Nelfinavir

• Atazanavir

• Fosamprenavir

Many antivirals that Belsomra interacts with are long-term medications. In some cases, taking a lower Belsomra dose can manage this interaction. Other times, you may need to take a different sleep medication.

7. Certain antibiotics, such as clarithromycin

Some antibiotics slow the breakdown of Belsomra in your body. This can cause more Belsomra side effects.

Notable antibiotics that interact with Belsomra include:

• Clarithromycin

• Ciprofloxacin

• Erythromycin (Ery-Tab)

Your Belsomra dose may need to be lowered or stopped depending on which antibiotic you’re taking. For example, a lower dose of Belsomra (5 mg) may still be OK with ciprofloxacin. But you should completely avoid combining Belsomra and clarithromycin.

8. Certain anti-seizure medications, such as carbamazepine

Some anti-seizure medications interact with Belsomra. But unlike the interactions discussed above, these medications can make Belsomra less effective.

Certain anti-seizure medications speed up how quickly your body breaks down Belsomra. So the effects of Belsomra won’t be as strong, and it may not be as helpful for sleep. Examples of interacting anti-seizure medications include carbamazepine and phenytoin.

Ask your prescriber which sleep medication is best for you. Belsomra may still work well for you despite this interaction. But other people may need to switch to a different sleep medication. Some sleep medications, such as zaleplon, are less affected by these anti-seizure medications.

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Written by:

Tegan Smedley, PharmD, APh

Tegan Smedley, PharmD, APh, has 10 years of experience as a pharmacist. She has worked in a variety of settings, including retail, hospital, and ambulatory care.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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