Alcohol, Benzodiazepines, and More: 9 Buprenorphine Interactions to Watch For

Buprenorphine is a first-choice medication for treating opioid use disorder (OUD). Some buprenorphine formulations are also approved to treat chronic pain.

Buprenorphine is available in many forms and strengths. For OUD, it comes as sublingual tablets (formerly Subutex) and injections (Sublocade, Brixadi). It’s also available in combination with naloxone as tablets and film (Suboxone). Other buprenorphine formulations, like buccal films (Belbuca) and skin patches (Butrans), are approved only for chronic pain.

Buprenorphine works in a unique way. It’s considered a partial opioid agonist, which means it has some opioid properties. Because of its opioid-like ability to cause drowsiness and dizziness, buprenorphine has many drug interactions. Here, we’ll cover what you need to know about nine buprenorphine interactions and how to manage them.

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Buprenorphine interactions at a glance

Below is an overview of common medications that may cause buprenorphine interactions. This list is not all-inclusive, so it’s always best to share a medication list with your healthcare team. They can help screen for buprenorphine interactions and keep you safe.

1. Benzodiazepines, such as alprazolam

Benzodiazepines are used for many health conditions, such as anxiety and panic attacks. Examples include alprazolam, clonazepam, and lorazepam. Taking benzodiazepines with buprenorphine can have dangerous effects.

Benzodiazepines are sedative medications. Dizziness and drowsiness are common side effects. When they’re taken with buprenorphine, these side effects may worsen. This makes you more likely to experience severe sedation, falls, and injuries. You’re also more likely to experience slowed breathing and overdose.

If you take buprenorphine, your healthcare team can help you find safer alternatives to benzodiazepines.

Good to know: Overdose is a medical emergency. Signs can include slow breathing, bluish skin, or unconsciousness. If someone is experiencing these symptoms, act fast and administer naloxone (Narcan, Zimhi) or nalmefene (Opvee, Zurnai) right away. These lifesaving medications can reverse the effects of an opioid overdose, including buprenorphine. Then call 911. Even after administration of one medication, the individual will still need medical attention.

2. Alcohol

Alcohol interacts with many medications. When combined with buprenorphine, it can increase your risk of severe sedation, slowed breathing, and overdose.

If you take buprenorphine, it’s best to steer clear of alcohol to minimize the risk of these side effects. It’s important to remember that no amount is considered safe. If you need help cutting out drinking so you can take buprenorphine safely, talk to your healthcare team about resources.

3. Muscle relaxers, such as tizanidine

Muscle relaxers may be used to relieve short-term muscle pain or spasms. Examples include carisoprodol, cyclobenzaprine, and tizanidine.

It’s safest to avoid muscle relaxers if you’re taking buprenorphine. This is because muscle relaxers affect more than your muscles. They also suppress your central nervous system, which includes your brain and spinal cord. This can lead to drowsiness and dizziness. Slowed breathing is also a risk, especially when taken in larger doses. Taking muscle relaxers with buprenorphine increases your risk of severe drowsiness, slowed breathing, and overdose.

EXPERT PICKS: WHAT TO READ NEXT

• Are medications recommended to treat opioid use disorder? Yes. Find out why medications are the mainstay of treatment for opioid use disorder.

• How does buprenorphine work? Learn how this unique medication treats opioid use disorder and chronic pain.

• What are common buprenorphine side effects? Buprenorphine can cause dizziness, drowsiness, and more. Learn what to watch for.

Ask a healthcare professional about potential safer alternatives to treat strained muscles. An OTC pain reliever, such as ibuprofen (Advil, Motrin) or acetaminophen (Tylenol), may be safer. A topical cream may work too. Nonmedication treatments like heat or cold therapy can also be effective.

4. Sleep medications, such as zolpidem

Medications used to treat insomnia (trouble sleeping) can cause drowsiness, dizziness, and slowed breathing. When combined with buprenorphine, these side effects may be severe. This can make you more likely to have falls and injuries. Examples of medications used to help people sleep include:

• Z-drugs, such as zolpidem

• Some OTC antihistamines, such as diphenhydramine

• Antidepressants, such as trazodone (used off-label for sleep)

• Orexin receptor antagonists, such as Dayvigo (lemborexant)

• Melatonin and the melatonin receptor agonist ramelteon (Rozerem)

If you need medication to help you sleep, tell your prescriber before starting buprenorphine. Burprenorphine sometimes causes sleep issues, so tell your prescriber if you start to have trouble sleeping.

5. Medications that increase serotonin, such as Lexapro

Serotonin is a natural chemical in your body that helps regulate mood, digestion, and more. Many medications increase serotonin levels, including buprenorphine. But when multiple serotonin-boosting medications are combined, serotonin levels may rise too high. This can lead to serotonin syndrome. Symptoms may include sweating, fever, or confusion.

Examples of medications and supplements that increase serotonin when combined with buprenorphine include:

• Selective serotonin reuptake inhibitors (SSRIs), such as citalopram and escitalopram

• Tricyclic antidepressants, such as amitriptyline and nortriptyline

• Monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil) and selegiline (Emsam, Zelapar)

• St. John’s wort

This isn’t a complete list. Your healthcare team can help you determine if you take too many medications that increase serotonin. Some medications, such as MAOIs, need to be avoided with buprenorphine altogether. In fact, it is generally not recommended to take  MAOIs and buprenorphine within 14 days of each other. But other medications may not need to be avoided completely. Your prescriber will review your risks.

6. Some antibiotics, such as ciprofloxacin

Buprenorphine is metabolized (broken down) by enzymes (proteins) in our liver. Some antibiotics can change how fast these enzymes work. This can cause an interaction with buprenorphine.

If liver enzymes are slowed down, buprenorphine levels may increase. This makes side effects more likely. Medications that can have this effect include erythromycin, ciprofloxacin, and clarithromycin (Biaxin XL).

But if a medication speeds up liver enzymes, buprenorphine may metabolize too quickly. This lowers the level of the medication in your body, making it less effective. Rifampin, an antibiotic for tuberculosis, causes this type of interaction.

Make sure your prescribers know that you’re taking buprenorphine. This includes urgent care and telehealth prescribers. They can help choose an antibiotic that won’t interact with buprenorphine.

7. Some antifungals, such as fluconazole

Antifungals treat conditions like thrush, yeast infections, and ringworm. Not all antifungals interact with buprenorphine. But some oral antifungal treatments, like azole antifungals, may. Examples include fluconazole, ketoconazole, and itraconazole.

Some azole antifungals block enzymes that metabolize buprenorphine. This can increase buprenorphine levels and increase your risk of side effects. If you need an antifungal, talk to your prescriber. They can help you choose one that doesn’t interact with buprenorphine.

8. HIV medications, such as atazanavir

Over 30 medications are FDA approved to treat HIV. Not all interact with buprenorphine, but there are two medication classes to be aware of: protease inhibitors and non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Both of these medication classes affect enzymes that metabolize buprenorphine. Protease inhibitors block metabolism, leading to an increased risk for side effects. NNRTIs have varying effects. This can result in buprenorphine levels that are too high or too low (which can make buprenorphine less effective or increase the risk of side effects).

Protease inhibitors that can interact with buprenorphine include atazanavir and ritonavir-containing medications. This includes the COVID-19 treatment Paxlovid, which contains ritonavir. NNRTIs that can interact with buprenorphine include medications containing efavirenz and nevirapine.

Your healthcare team will help you manage these interactions. In some cases, they may recommend watching for side effects. In other cases, they may adjust your dosing regimen.

9. Some seizure medications, such as phenytoin

Some common seizure medications can interact with buprenorphine. They do this by speeding up how quickly it metabolizes. This can lead to buprenorphine levels that are too low, making it less effective. Examples include carbamazepine and phenytoin.

If you’re taking a seizure medication and buprenorphine, or your dose of either medication needs to change, tell your healthcare team. They will adjust your medications and keep you safe. But don’t adjust doses of your seizure medications or buprenorphine on your own.

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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:

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:

Bailey E. Eason, PharmD, MS, BCPS

Bailey Eason has been licensed for 6 years and has held licenses in three states (North Carolina, Virginia, and Illinois). She has held positions as a health-system pharmacy administration resident, operating room pharmacy manager, pharmacy manager of clinical operations: surgery, neurology and controlled substances, and most recently as program director  of drug diversion for a large academic health system.

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