Buprenorphine and Nefazodone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Nefazodone
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Taking buprenorphine with nefazodone needs some care. Nefazodone slows down a liver enzyme (called CYP3A4) that normally breaks down buprenorphine. When that clean-up slows, buprenorphine can build up in your body. That can mean stronger, longer opioid effects, such as feeling very sleepy, foggy, or breathing more slowly than usual.
On top of that, both medicines can raise serotonin levels in the brain, so together they can slightly raise the risk of a reaction called serotonin syndrome (things like restlessness, sweating, shivering, fast heartbeat, or muscle twitching).
The good news is your care team can manage this by adjusting your dose and watching you closely. Keep taking both as prescribed and let your pharmacist or doctor know about the combination.
Effect: Increased buprenorphine exposure plus additive serotonergic risk.
- Mechanism: Nefazodone is a potent CYP3A4 inhibitor, reducing buprenorphine metabolism and raising plasma levels (buprenorphine is active, not a prodrug, so effect increases). Both agents are serotonergic, giving additive PD risk.
- Direction: Enhanced/prolonged opioid effect; risk of sedation and respiratory depression, plus serotonin syndrome.
- Severity/Evidence: Major; probable. Onset unspecified.
- Management: If nefazodone is needed, consider reducing buprenorphine dose until stable and monitor frequently for sedation/respiratory depression. On nefazodone discontinuation, anticipate withdrawal and consider dose increase. For long-acting subQ formulations, monitor for over-medication or inadequate levels. Watch for serotonin syndrome, especially at initiation/titration.
What happens
An increased risk of serotonin syndrome, increased buprenorphine exposure and an increased risk of buprenorphine-related adverse events
Interaction Deep Dive
Taking buprenorphine together with CYP3A4 inhibitors can raise buprenorphine plasma concentrations and potentially cause prolonged opioid effects. When a patient on buprenorphine requires a CYP3A4 inhibitor, consider lowering the buprenorphine dose until steady drug effects are reached, and check frequently for sedation and respiratory depression. Conversely, if a CYP3A4 inhibitor is stopped in a patient being treated with buprenorphine, consider raising the buprenorphine dose until stable effects are obtained, while watching for signs of opioid withdrawal2. Should dose adjustment prove impossible once the CYP3A4 inhibitor is gone, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients transitioned from transmucosal buprenorphine given alongside CYP3A4 inhibitors, verify that the plasma buprenorphine concentration delivered by subQ buprenorphine is sufficient. For those already receiving subQ buprenorphine who need a CYP3A4 inhibitor, watch for signs of over-medication. If buprenorphine toxicity develops and the coadministered drug cannot be reduced or stopped, decrease the buprenorphine dose instead. Furthermore, when buprenorphine must be used together with a serotonergic agent, monitor the patient for signs and symptoms of serotonin syndrome, particularly at the start of treatment and during dose changes, and stop buprenorphine if serotonin syndrome is suspected 1.
Why it happens (mechanism)
Additive serotonergic effects; inhibition of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be managed with careful dosing and monitoring.
- Your buprenorphine dose may need to be adjusted and individualized by your care team, often lowered while you are on nefazodone and adjusted again if nefazodone is stopped.
- Your team may monitor you more closely for excess sedation, slowed breathing, or opioid withdrawal.
- Watch for signs of serotonin syndrome (agitation, sweating, shivering, fast heartbeat, muscle twitching), especially when starting or changing doses.
- Get emergency help for very slow or shallow breathing, extreme drowsiness, or these serotonin symptoms, and tell your pharmacist or doctor about both drugs.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of concurrently administered CYP3A4 inhibitors on buprenorphine exposure in individuals receiving subQ buprenorphine has not been investigated; nonetheless, such interactions have been demonstrated in studies employing transmucosal buprenorphine. The effects of buprenorphine may vary according to the route of administration 1.
Common questions
Can I take Buprenorphine and Nefazodone together?
Nefazodone can raise buprenorphine levels and add serotonin-related risk, so watch for extra sedation, slowed breathing, or serotonin syndrome. Do not change anything on your own; your care team can adjust the dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Nefazodone interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Buprenorphine and Nefazodone interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination can be managed with careful dosing and monitoring. Your buprenorphine dose may need to be adjusted and individualized by your care team, often lowered while you are on nefazodone and adjusted again if nefazodone is stopped. Your team may monitor you more closely for excess sedation, slowed breathi… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Buprenorphine or Nefazodone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: ZUBSOLV(R) sublingual tablets, buprenorphine naloxone sublingual tablets. Orexo US Inc (per FDA), Morristown, NJ, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about Nefazodone
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