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What does Suboxone interact with?
Suboxone interacts most importantly with alcohol, benzodiazepines, and other sedating medications. These combinations can increase the risk of respiratory depression. All medications and substances should be discussed with your physician.
CNS depressants
The most clinically significant interactions involve CNS depression.
The most important interaction category for buprenorphine is co-use with other central nervous system (CNS) depressants — substances that slow brain and respiratory activity. Combining buprenorphine with these substances increases the risk of respiratory depression.
Alcohol
Alcohol is a CNS depressant. Combining alcohol with buprenorphine increases the risk of respiratory depression — slower, shallower breathing — particularly at higher buprenorphine doses or with larger amounts of alcohol. The risk is real but lower than the same combination with full opioid agonists, due to buprenorphine's ceiling effect. Alcohol use should be discussed with the prescribing clinician.
Benzodiazepines
Benzodiazepines (Xanax, Klonopin, Valium, Ativan) are CNS depressants. Co-prescribing benzodiazepines and buprenorphine carries increased respiratory risk, though evidence increasingly suggests that buprenorphine should not be withheld from patients who are also prescribed benzodiazepines — tapering benzodiazepines is preferable to denying buprenorphine. All prescribed medications should be reviewed with the prescribing clinician.
Sleep medications and muscle relaxants
Medications like carisoprodol (Soma), cyclobenzaprine, zolpidem, and similar drugs also carry CNS depression risk when combined with buprenorphine. A full medication list is important for clinical review.
Kratom
Kratom and buprenorphine — a clinically relevant interaction.
Kratom (Mitragyna speciosa) contains alkaloids — particularly mitragynine and 7-hydroxymitragynine (7-OH) — that act on opioid receptors. This creates a clinically meaningful interaction with buprenorphine.
Does buprenorphine block kratom?
Buprenorphine has high receptor affinity, it may reduce the opioid-receptor effects associated with kratom alkaloids. People taking buprenorphine who also use kratom may experience reduced kratom effects. This is not guaranteed — the degree of blockade depends on dose, timing, and individual factors.
Combination risk
Kratom alkaloids, like other opioid-acting substances, carry additive CNS depression risk when combined with buprenorphine. Because kratom has opioid-like activity, combining it with buprenorphine may increase sedation or other adverse effects. Kratom use should be discussed with the prescribing clinician. See our kratom treatment page for more on kratom dependence.
Other medications
Drug interactions involving buprenorphine metabolism.
Buprenorphine is primarily metabolized by the CYP3A4 enzyme system. Medications that inhibit or induce CYP3A4 can affect buprenorphine blood levels.
CYP3A4 inhibitors
Certain antibiotics (clarithromycin, erythromycin), antifungals (ketoconazole, fluconazole), and HIV medications can inhibit CYP3A4 and increase buprenorphine blood levels — potentially increasing sedation or side effects.
CYP3A4 inducers
Rifampin (an antibiotic), carbamazepine (an anticonvulsant), and some other medications can induce CYP3A4 and decrease buprenorphine blood levels — potentially reducing its effectiveness and triggering withdrawal symptoms.
Sources
Where this information comes from.
Suboxone Prescribing Information
Full drug interactions section from the FDA prescribing information for buprenorphine/naloxone.
ASAM National Practice Guideline (2020)
Clinical guidance on buprenorphine drug interactions and co-occurring substance use.
Demonstrates that 7-hydroxymitragynine — a kratom metabolite — mediates analgesic effects via the mu-opioid receptor, explaining its clinical interaction with buprenorphine.
WHO ECDD — Pre-Review Report on Kratom, Mitragynine, and 7-Hydroxymitragynine
World Health Organization expert review of kratom pharmacology, opioid receptor activity, and clinical significance.
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Common questions
Frequently asked
Can I take over-the-counter pain medication while on Suboxone?
Non-opioid OTC medications like acetaminophen or ibuprofen are generally safe to take alongside buprenorphine. Always disclose all medications to your physician.
Does grapefruit affect Suboxone?
Grapefruit and grapefruit juice can inhibit CYP3A4, the enzyme that metabolizes buprenorphine, potentially increasing medication levels. This is not commonly a significant clinical concern but is worth noting.
Can I take antidepressants with Suboxone?
Most antidepressants can be used alongside buprenorphine. Some combinations require closer monitoring. Your prescribers should be aware of all medications you are taking.
