Buprenorphine and Mitotane: 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
Mitotane
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.
Let me explain what's going on here. Mitotane speeds up the liver enzyme (called CYP3A4) that breaks down your buprenorphine. That means your body clears the buprenorphine faster, so there's less of it working in your system.
The practical result is that your buprenorphine may not work as well. You could feel more pain or notice opioid withdrawal symptoms, like restlessness, sweating, chills, or an upset stomach. The good news is your care team can manage this by adjusting your dose and watching how you're doing. Please don't change anything on your own. Just let your pharmacist or doctor know you take both.
Effect: Mitotane is a potent CYP3A4 inducer and buprenorphine is a CYP3A4 substrate. Coadministration increases buprenorphine metabolism, reducing its plasma exposure and analgesic/maintenance efficacy, with risk of opioid withdrawal.
- Direction: Reduced buprenorphine effect (neither drug is a prodrug here).
- Evidence: Probable; severity major; onset unspecified (mitotane induction is prolonged in onset and offset).
- Management: If mitotane is required, consider titrating buprenorphine upward to stable effect and monitor for withdrawal. On mitotane discontinuation, anticipate rising buprenorphine levels; consider dose reduction and monitor for respiratory depression. Long-acting subQ formulations may need conversion to a formulation allowing precise titration.
What happens
Reduced buprenorphine exposure and reduced efficacy of buprenorphine
Interaction Deep Dive
Combining buprenorphine with a CYP3A4 inducer can trigger opioid withdrawal because buprenorphine plasma levels fall. When a patient on buprenorphine needs 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 being stopped in a patient receiving buprenorphine, consider lowering the buprenorphine dose and monitoring for respiratory depression2. Should dose adjustment prove impossible once the CYP3A4 inducer is gone, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients being converted from transmucosal buprenorphine given together with CYP3A4 inducers, verify that the plasma buprenorphine level 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 decreased or stopped, modify the buprenorphine dose. If the available doses cannot reach the target dose, use a buprenorphine formulation that permits more precise dose adjustments1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of buprenorphine
How to manage this interaction
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. Here's how a team typically handles this:
- Your buprenorphine dose may need to be adjusted and individualized while you are on mitotane, and your team may monitor you more closely for withdrawal (restlessness, sweating, chills, cramps).
- When mitotane is stopped, your buprenorphine level can rise again, so your team may lower the dose and watch for signs of over-sedation or slowed breathing.
- If you use a long-acting form, a formulation that allows finer dose changes may be preferred.
Tell your pharmacist or prescriber that you take both, and report any withdrawal symptoms or reduced pain relief.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of a concurrently administered CYP3A4 inducer on buprenorphine exposure in patients receiving subcutaneous buprenorphine has not been investigated; nevertheless, these interactions have been documented in trials involving transmucosal buprenorphine. Buprenorphine's effects may vary according to the route by which it is administered 1.
Common questions
Can I take Buprenorphine and Mitotane together?
Mitotane can lower buprenorphine levels and cause withdrawal or weaker effect; keep taking both as prescribed and let your care team adjust the dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Mitotane 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 Mitotane interaction managed?
Keep taking both medications exactly as prescribed unless your care team tells you otherwise. Here's how a team typically handles this: Your buprenorphine dose may need to be adjusted and individualized while you are on mitotane, and your team may monitor you more closely for withdrawal (restlessness, sweating, chills, cramps). When mitotane is stopped, your buprenorphine level can rise again, so… 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 Mitotane 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 Mitotane
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