Enzalutamide and Buprenorphine: 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
Enzalutamide
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.
These two medicines can work against each other. Enzalutamide (Xtandi) speeds up the liver enzyme that breaks down buprenorphine. That means your body clears the buprenorphine faster, so there is less of it in your blood and it may not work as well.
If you take buprenorphine for pain or for opioid treatment, you might notice it wearing off or feel withdrawal symptoms like aches, sweating, chills, or restlessness. The good news is your care team can manage this by adjusting your buprenorphine dose and watching how you respond. Keep taking both medicines as prescribed, and let your doctor or pharmacist know how you feel.
Effect: Enzalutamide, a strong CYP3A4 inducer, increases CYP3A4-mediated metabolism of buprenorphine, lowering buprenorphine plasma concentrations and reducing efficacy (risk of opioid withdrawal).
- Direction: Reduced buprenorphine exposure/effect (buprenorphine is not a prodrug; the parent drug's activity is diminished).
- Evidence: Probable; severity major; onset unspecified (induction develops over days to weeks).
- Management: If the inducer is required, titrate buprenorphine upward to stable effect and monitor for withdrawal. On enzalutamide discontinuation, reduce buprenorphine dose and monitor for respiratory depression. Favor formulations allowing precise titration; for subQ depot products, confirm adequate levels or monitor for withdrawal.
What happens
Reduced buprenorphine exposure and reduced efficacy of buprenorphine
Interaction Deep Dive
Because plasma levels of buprenorphine fall when it is taken together with a CYP3A4 inducer, symptoms of opioid withdrawal can develop. When a patient on buprenorphine must also receive a CYP3A4 inducer, one option is to raise the buprenorphine dose until stable drug effects are reached while watching for withdrawal. Conversely, if a CYP3A4 inducer is stopped in someone being treated with buprenorphine, consider lowering the buprenorphine dose and observe for respiratory depression2. Should dose adjustment prove impossible once the CYP3A4 inducer is removed, move the patient back to a buprenorphine formulation that allows finer dose titration. For patients switched from transmucosal buprenorphine given alongside CYP3A4 inducers, confirm that the plasma buprenorphine concentration achieved with subQ buprenorphine is sufficient. In those already receiving subQ buprenorphine who need to start a CYP3A4 inducer, monitor for withdrawal. When the buprenorphine dose is insufficient while the concomitant drug is present, and that concomitant drug cannot be lowered or stopped, modify the buprenorphine dose. If the available doses cannot reach the target dose, use a buprenorphine formulation that allows more precise dose adjustments1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both medicines exactly as prescribed. Do not change or stop either one on your own. Your care team can manage this by tailoring your buprenorphine dose and watching you closely.
- Your buprenorphine dose may need to be adjusted and individualized while you are on enzalutamide to keep it working and prevent withdrawal.
- If enzalutamide is later stopped, your team may lower the buprenorphine dose and watch for over-sedation or slowed breathing.
- A buprenorphine form that allows more precise dosing may be preferred.
- Tell your pharmacist or prescriber if you feel withdrawal (aches, sweating, chills, cravings) or if your pain control slips.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of concurrent CYP3A4 inducer administration on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, these interactions have been demonstrated in studies employing transmucosal buprenorphine. Buprenorphine's effects may vary according to the route of administration 1.
Common questions
Can I take Enzalutamide and Buprenorphine together?
Enzalutamide can lower buprenorphine levels and cause it to work less well or trigger withdrawal, so your doctor may adjust your buprenorphine dose and monitor you. Keep taking both as prescribed and report any withdrawal symptoms. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Enzalutamide and Buprenorphine 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 Enzalutamide and Buprenorphine interaction managed?
Keep taking both medicines exactly as prescribed. Do not change or stop either one on your own. Your care team can manage this by tailoring your buprenorphine dose and watching you closely. Your buprenorphine dose may need to be adjusted and individualized while you are on enzalutamide to keep it working and prevent withdrawal. If enzalutamide is later stopped, your team may lower the buprenorphin… 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 Enzalutamide or Buprenorphine 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 Enzalutamide
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