Suboxone Drug Interactions

Clinical Reviewer

Suboxone is a safe medication with few serious drug interactions.

In general, benzodiazepines, alcohol and opioids, as well as muscle relaxers, barbiturates and kratom are advised to be avoided while on Suboxone. However, mixing prescription painkillers or heroin with these same medications is more dangerous.

Certain medications can also impact the effectiveness of Suboxone, including some antibiotics, HIV medications and even St. John’s Wort supplements. You don’t necessarily have to stop taking these medications while on Suboxone, but your Suboxone dosing may need to be adjusted accordingly.

Of course, you should always talk to your Suboxone doctor before you start a new medication or supplement or if you start to feel any withdrawal or other unusual symptoms.

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The Most Dangerous Interactions with Suboxone

Top 3 Most Common Dangerous Interactions

Substance Consequence of Mixing with Suboxone
Benzodiazepines High risk of breathing problems. Those combining Suboxone with benzodiazepines are twice as likely to end up in the hospital.
Alcohol Can make you extra sleepy and slow down your breathing to the point of potential death.
Opioids
OxyContin (Oxycodone), Vicodin (Hydrocodone), Morphine, Ultram (Tramadol), Methadone
Risk of overdose by chasing the “high” that Suboxone is blocking or because Suboxone allows sobriety from full opioids, which lowered the opioid tolerance.

Doctor Recommendations for Mixing Benzodiazepines (ie. Xanax / Klonopin) With Suboxone

Suboxone can usually be started when taking benzodiazepines (“benzos”). But, self-medicating with benzodiazepines can be fatal. Your Suboxone provider can provide you safe medications to use with Suboxone that help anxiety, sleep or whatever issue the benzodiazepine is supposed to solve. 

Taking benzodiazepines (“benzos”) with full opioids is more dangerous than taking the same benzodiazepines with Suboxone. Being on Suboxone and benzodiazepines simultaneously is acceptable, but requires more caution.

Your doctor should test for benzodiazepines before starting you on Suboxone, so it’s best to be honest and upfront about your use, including the amount.

Depending on the benzodiazepine use, other medications involved, the patient’s health and history and the doctor’s experience with Suboxone, some patients using benzodiazepines are referred to inpatient facilities to start induction on Suboxone and detox off benzodiazepines. At Symetria, we try to help patients directly as we know many patients don’t end up going to the inpatient referral.

Benzodiazepines should be tapered down slowly to avoid withdrawal symptoms, psychological effects like panic attacks and seizures or drops in blood pressure that can be fatal. The process of safely tapering off of benzodiazepines often takes many months if benzodiazepine use has been chronic.

In cases of a co-existing benzodiazepine use disorder, often the medical recommendation is to go to an inpatient detox facility or hospital for 7+ days to start a detox from the benzodiazepines. There you will be medically monitored to make sure no medical complications arise during your detox. Also while there, a psychiatric provider is able to evaluate you, often switch you to safer benzodiazepines and other comfort medications, and start a plan to gradually taper you off of all benzodiazepines entirely. Patients are often able to be started on Suboxone before being discharged from detox.

After completing short term detox from the benzodiazepine use, and a benzodiazepine taper plan is in place, then treatment for opioid use disorder can be continued safely and fully outpatient.

Do not self-medicate with benzodiazepines. Developing a physical dependence on benzodiazepines complicates opioid issues and is likely to land patients in the hospital. Benzodiazepines will not make you feel better! It will make treatment more complex and prolong the time it takes for you to actually feel better. Any unpleasant symptoms you still feel while on Suboxone can be managed without turning to benzodiazepines.

Benzodiazepines are not often prescribed while on Suboxone. Tell your doctor about your Suboxone medication to stay safe.  

Anxiety and insomnia are the most common reasons people are prescribed or self-medicate with benzodiazepines.

Sometimes the symptoms are directly related to opioid withdrawal. In that case, increasing the Suboxone dosage is enough to stop the anxiety or insomnia.

If you are still feeling these unpleasant mental symptoms after detoxing from benzodiazepines and stabilizing on Suboxone, your Suboxone doctor should be working with you to feel better. You should never feel like you need to self-medicate. Newer antidepressants are often good alternatives that are much safer than benzodiazepine. 

Doctor Recommendations for Drinking Alcohol On Suboxone

Alcohol is a depressant and does not mix well with other depressants, especially opioids. This includes Suboxone (since Suboxone is a partial opioid). Both alcohol and Suboxone slow down brain and body functions. When critical functions like breathing are slowed too much, overdose occurs.

The majority of people that die with Suboxone in their system also have alcohol in their system.  

Alcohol can be fatal if consumed in excess even without a Suboxone interaction (ie. alcohol poisoning). Not drinking any alcohol is always safest — especially since moderation tends to be harder for someone struggling with addiction.

If you feel you are using alcohol as a substitute for opioids to numb your feelings, you are at high risk of a serious interaction. Seek help with your mental health ASAP. Therapy should be offered by your Suboxone clinic. Medications like antidepressants can also be helpful to deal with underlying issues like depression or anxiety. You can get to a place where you don’t feel you need substances to cope.

If someone you know continues to drink alcohol while taking Suboxone, keep Narcan on-hand to reverse an opioid overdose. Overdose cases involving Suboxone are almost always accidental.

The risk of fatal outcomes increases dramatically when getting Suboxone from an illicit source, taking more Suboxone than directed by a doctor or combining with additional depressant substances (ie. mixing Suboxone AND alcohol AND benzodiazepine, muscle relaxants, etc).

While plenty of patients taking Suboxone as prescribed have had a drink or two without issue, accept that the combination is known to be dangerous and act accordingly — either with extreme caution or by avoiding alcohol altogether.

Taking Opioids With Suboxone

Medical literature cites that mixing Suboxone with opioids increases the risk for opioid overdose. However, several case studies actually show Suboxone reversing heroin overdoses. ⓘ 

The risks of opioid use while on Suboxone is more related to chasing the “high” that Suboxone is blocking, taking the same opioid dosing after even brief periods of sobriety or in combination with other depressant drugs like benzodiazepines or alcohol.

Suboxone will block much of the “high”. Suboxone is already occupying the opioid receptors in the brain, so other opioids (like prescription painkillers, heroin or methadone) will not be able to attach as well. As a result, the opioids won’t cause their usual degree of effect.

Suboxone allows patients to avoid taking other opioids. Tolerance lowers even if they are stopped for a short time, and even if taking Suboxone. Attempting to take the same amount of opioids as before even this short sobriety period can be fatal.

When patients learn (sometimes the hard way) that using opioids will not give the high they are looking for and can cause 10/10 withdrawal sickness, it’s clearly not worth the relapse. A better way to address intense, lingering opioid craving is to talk to your medical provider about increasing your Suboxone dosage.

For chronic pain patients, Lyrica can be a good, non-opioid option. Generics are now available to make Lyrica more affordable.

If a patient stops taking Suboxone for more than 1-2 days, returns to opioid use, then tries to restart Suboxone, the patient will likely experience sudden and severe opioid withdrawal symptoms that mimic flu-like symptoms (muscle aches, nausea, vomiting, sweating, chills, tremors and diarrhea). This is called precipitated withdrawal and can start within 30 minutes after taking Suboxone.

In order to prevent precipitated withdrawal, the patient should be in mild to moderate opioid withdrawal before restarting Suboxone. Comfort medications can help make the opioid withdrawal symptoms manageable until ready to restart the Suboxone.

Fortunately, if a patient returns to opioid use but hasn’t stopped taking Suboxone (or only stopped Suboxone for 1-2 days) then the Suboxone can be safely resumed with minimal chance of precipitated withdrawal.

Therefore, if a patient stops taking the Suboxone any returns to other opioid use for any period of time, it is best to inform your Suboxone provider of your exact situation, since the treatment recommendations can vary.

Less Common Dangerous Interactions with Suboxone

In general, these medications are also recommended to be avoided.

Anything that is a depressant or slows down the body is potentially dangerous, since Suboxone is also a depressant that slows down the body.

SubstanceConsequence of Mixing with Suboxone

Muscle Relaxants
Flexeril (Cyclobenzaprine), Soma (Carisoprodol), Zanaflex (Tizanidine), Baclofen

High risk of making you very sleepy and causing serious breathing problems. 

Barbiturates
Phenobarbital, Seconal (Secobarbital)

High risk of making you very sleepy and causing serious breathing problems.
KratomCan cause a new substance use issue. (Suboxone is actually used to detox people off of Kratom). Also, because Kratom acts on opioid receptors, a higher risk of overdose seems likely though is under researched. 

Certain Antipsychotics
Prochlorperazine (Compazine)

The data is not fully studied, but there are enough case studies to recommend finding an attentive medication combination.

MAOI Anti-Depressants 
Selegiline (Eldepryl / Zelapar), Isocarboxazid (Marplan), Phenelzine (Nardil), Tranylcypromine (Parnate)

Can cause serotonin toxicity, which includes muscle tremors or rigidity, fever, fast heartbeat, an altered mental state and can be fatal if not treated.  

Doctor Recommendations for Taking Antidepressants With Suboxone

Antidepressants are commonly prescribed with Suboxone. Antidepressants classified as SSRI, SNRI or TCA are most common. These antidepressant medications are perfectly safe to use with Suboxone. The only antidepressants that pose a risk of rare interaction are classified as MAOIs, which are older and less commonly prescribed.

Be open to using antidepressants as part of your addiction treatment. If you feel weird, restless or confused when combining Suboxone with an antidepressant, talk to your provider about trying a different option or changing dosing.

The research is clear that treating underlying issues like depression and anxiety dramatically increase the likelihood of staying healthy long-term.

Other Interactions with Suboxone (Use Caution)

The medical literature generally advises caution rather than outright avoidance with these substances. The key is to be aware of potential risks and to keep your medical team updated on any changes to the medications or supplements you take.

SubstanceConsequence Mixing with Suboxone

Sleeping Pills
Ambien (Zolpidem), Lunesta (Eszopiclone), Sonata (Zaleplon)

Risk of making you too sleepy and causing dangerous breathing issues. There are better options for improving sleep. See: Sleeping Tips After Opioid Addiction

Dextromethorphan
Robitussin DM, Delsym, Mucinex DM, Coricidin HBP Cough & Cold, Vicks DayQuil Cough, NyQuil Cough

Increased risk of serotonin syndrome and respiratory depression, both of which can be life-threatening in severe cases. Do not abuse these medications. 

Clonidine
Catapres, Kapvay, Nexiclon XR, Jenloga

Can lead to excessive sedation, dangerously low blood pressure (hypotension) and respiratory depression, which can be fatal.
GabapentinSometimes recommended for anxiety or unmanaged pain, but always should be used under medical supervision because the combination has caused fatal issues (severe drowsiness and respiratory depression).
AnesthesiaSuboxone can change the response to certain anesthesias, which may affect pain management and sedation levels during and after surgery. Suboxone patients can definitely have surgeries, but tell your anesthesiologist about your Suboxone use. 
KavaCan make the sleepy effects of Suboxone stronger and doesn’t serve a confirmed medical purpose. Talk to your provider about better options for anxiety or sleep issues.
Valerian RootCan make the sleepy effects of Suboxone stronger and doesn’t serve a confirmed medical purpose. Talk to your provider about better options for sleep or anxiety issues.

Risk-Benefit of Each Medication is Different for Each Patient

Risk Benefits Of Medications Is Different for Each Patient

Interactions with Suboxone That Impact Effectiveness

If you notice Suboxone seems less effective after starting a new medication or supplement, it’s very possible the new substance is causing issues.

Certain medications can either increase or decrease the blood levels of Suboxone by affecting its metabolism. This can lead to reduced effectiveness or increased side effects of Suboxone.

These medications CAN be taken safe with Suboxone. Just be sure to tell your doctor about the other substances you are taking to ensure Suboxone is effective in preventing cravings and subduing withdrawal symptoms.

Your medical team can consider stopping the new medication or supplement, changing to an alternative or altering the Suboxone dose. 

SubstanceConsequence Mixing with Suboxone

HIV Protease Inhibitors
Ritonavir (Norvir, Reyataz), Indinavir (Crixivan), Saquinavir (Invirase, Fortovase), Nelfinavir (Viracept), Fosamprenavir (Lexiva), Atazanavir (Kaletra), Tipranavir (Aptivus), Darunavir (Prezista)

Can make the effects of Suboxone too strong. Newer HIV medications like dolutegravir (Tivicay) or bictegravir (Biktarvy) tend to have less interaction issues

Certain Antifungal Agents
Ketoconazole (Nizoral), Itraconazole (Sporanox), Voriconazole (Vfend), Fluconazole (Diflucan), Posaconazole (Noxafil)

Can make the effects of Suboxone too strong.

Certain Antibiotics
Clarithromycin (Biaxin), Erythromycin (Ery-Tab, EryPed, Erythrocin), Rifampin (Rifadin), Rifabutin (Mycobutin), Rifapentine (Priftin)

Can cause varying effects. For example, Clarithromycin and Erythromycin increase the levels of Suboxone in the blood, while Rifampin can decrease the levels and therefore effectiveness.

Certain Anticonvulsants
Phenobarbital, Phenytoin (Dilantin), Carbamazepine (Tegretol), Oxcarbazepine (Trileptal)

Can make Suboxone less effective, so it might not work as well.
Cimetidine
Tagamet
Can make the effects of Suboxone too strong.
St. John’s WortCan make Suboxone less effective, so it might not work as well.
Grapefruit Juice Can make the effects of Suboxone too strong.

Safe Medications With Suboxone

If you have questions about how specific medications interact with Suboxone not covered on this page, leave a comment to get answered by the medical team.

Substance Notes

Ondansetron
Zofran

Sometimes recommended for uncontrolled nausea. 
CaffeineNo known impact with Suboxone.

Ibuprofen
Motrin, Advil

No known impact with Suboxone.
CBDShould be OK, but stay aware of any adverse reactions you notice. 

How to avoid drug interactions while taking suboxone?

Start Suboxone in-person at an addiction clinic or hospital. Get the medication legally from a physician and take it as prescribed. Always disclose all medications you are taking before starting any new medications. If possible, avoid depressants including alcohol, benzodiazepines or opioids.

If you don’t have a Suboxone doctor you see regularly or if your doctors aren’t helping you navigate these kinds of details, consider switching. It may sound annoying, but you don’t know how much better you can feel to have a doctor who listens.

Get Help With Suboxone

Symetria doctors follow rigorous sourcing guidelines and cite only trustworthy sources of information, including peer-reviewed journals, court records, academic organizations, highly regarded nonprofit organizations, government reports and their own expertise with decades in the field.

Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-41. https://doi.org/10.1093/bja/aei210

Haverty, C., Niedermier, J., & Guirgis, H. (2020). 120 Laryngeal Dystonia and Buccolingual Crisis: Dystonic Reactions in 2 Patients Receiving Prochlorperazine During Suboxone Therapy. CNS Spectrums, 25(2), 278–278. https://doi.org/10.1017/s1092852920000383

Katie Thomas,Charles Ornstein. (2017, September 17). Amid Opioid Crisis, Insurers Restrict Pricey, Less Addictive Painkillers. ProPublica; ProPublica. https://www.propublica.org/article/insurers-limit-coverage-of-pricey-less-addictive-painkillers

Margareeta Häkkinen, Terhi Launiainen, Erkki Vuori, & Ilkka Ojanperä. (2011). Benzodiazepines and alcohol are associated with cases of fatal buprenorphine poisoning. European Journal of Clinical Pharmacology, 68(3), 301–309. https://doi.org/10.1007/s00228-011-1122-4

Welsh, C., Sherman, S. G., & Tobin, K. E. (2008). A case of heroin overdose reversed by sublingually administered buprenorphine/naloxone (Suboxone®). Addiction, 103(7), 1226–1228. https://doi.org/10.1111/j.1360-0443.2008.02244.x

Yokell, M. A., Zaller, N., Green, T. C., McKenzie, M., & Rich, J. D. (2012). Intravenous use of illicit buprenorphine/naloxone to reverse an acute heroin overdose. Journal of Opioid Management8(1), 63–66. https://doi.org/10.5055/jom.2012.0098

Zev Schuman‐Olivier, Hoeppner, B. B., Weiss, R. D., Borodovsky, J. T., Shaffer, H. J., & Albanese, M. J. (2013). Benzodiazepine use during buprenorphine treatment for opioid dependence: Clinical and safety outcomes. Drug and Alcohol Dependence, 132(3), 580–586. https://doi.org/10.1016/j.drugalcdep.2013.04.006

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2 Comments

  • This article is great. I know a lot of people that have been on suboxone for years, but still don’t know this type of information. For example, serotonin toxicity! Never heard of that before. Can you explain what that is please?

    I will be passing along this information.

    1. Serotonin toxicity (aka serotonin syndrome) is a rare condition where too much serotonin is being released in your brain. It is often caused by being on one or more medications that affects how serotonin is released and/or resorbed. The signs and symptoms include mental status changes (anxiety, restlessness, disorientation, delirium, agitation), neuromuscular activity (tremors, rigidity in muscles), and other findings (excessive sweating, fast heart rate, fever, hypertension, vomiting). In severe cases, it can cause seizures and death.

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    Symetria has addiction treatment clinics across the state. You can likely get scheduled TODAY — medications or therapy.

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