Apalutamide 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
Apalutamide
Buprenorphine
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.
Apalutamide (Erleada) can make your buprenorphine work less well. Apalutamide speeds up an enzyme in your liver (called CYP3A4) that breaks down buprenorphine. When buprenorphine is broken down faster, less of it stays in your body, so it may not control your pain or keep opioid withdrawal away as well as before.
You might notice withdrawal symptoms like anxiety, sweating, chills, stomach upset, or a racing heart. Please don't stop or change either medicine on your own. Your care team can manage this by tailoring your buprenorphine dose and watching you more closely. Let your pharmacist or doctor know if you feel any withdrawal.
Effect: Apalutamide, a strong CYP3A4 inducer, increases buprenorphine metabolism, lowering buprenorphine plasma concentrations and reducing efficacy. Neither agent is a prodrug here; this is a straightforward induction effect.
- Direction: Reduced buprenorphine exposure, risk of opioid withdrawal.
- Onset: Unspecified; enzyme induction typically develops over days to weeks.
- Evidence: Probable.
- Management: If apalutamide is needed, consider titrating buprenorphine up to stable effect and monitor for withdrawal. On apalutamide discontinuation, consider reducing buprenorphine and monitor for respiratory depression. For subQ/depot formulations, verify adequacy; if precise titration is needed, use a formulation allowing finer dose adjustment.
What happens
Reduced buprenorphine exposure and reduced efficacy of buprenorphine
Interaction Deep Dive
Combining buprenorphine with a CYP3A4 inducer can precipitate opioid withdrawal symptoms because buprenorphine plasma concentrations fall. When a patient on buprenorphine must also take a CYP3A4 inducer, consider raising the buprenorphine dose until stable drug effects are reached, while watching for withdrawal. Conversely, if a CYP3A4 inducer is stopped in a patient receiving buprenorphine, consider lowering the buprenorphine dose and monitoring for respiratory depression2. Should dose adjustment not be feasible once the CYP3A4 inducer is absent, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients being transitioned from transmucosal buprenorphine given together with CYP3A4 inducers, confirm through monitoring that the plasma buprenorphine level achieved with subQ buprenorphine is sufficient. When a patient already established on subQ buprenorphine needs a CYP3A4 inducer, monitor for withdrawal. If the buprenorphine dose proves inadequate while the concomitant drug is taken, and that concomitant drug cannot be decreased or stopped, modify the buprenorphine dose. When the available doses cannot deliver the desired dose, treat the patient with 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 medicines as prescribed unless your care team tells you otherwise. Here is what your team may do:
- Increase your buprenorphine dose (individualized by your team) until it works steadily, while watching for withdrawal.
- Watch you more closely for signs of withdrawal (anxiety, sweating, chills, muscle aches, stomach upset).
- If apalutamide is later stopped, they may lower your buprenorphine dose and monitor for slowed breathing.
- If you use a long-acting shot form, they may check that it is still keeping you comfortable, or switch to a form that allows finer dose adjustments.
Tell your pharmacist or prescriber right away if you notice withdrawal symptoms.
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 individuals 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 Apalutamide and Buprenorphine together?
Apalutamide can lower buprenorphine levels and trigger opioid withdrawal. Don't change anything yourself, but tell your care team so they can adjust your buprenorphine dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apalutamide 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 Apalutamide and Buprenorphine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Here is what your team may do: Increase your buprenorphine dose (individualized by your team) until it works steadily, while watching for withdrawal. Watch you more closely for signs of withdrawal (anxiety, sweating, chills, muscle aches, stomach upset). If apalutamide is later stopped, they may lower your buprenor… 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 Apalutamide 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 Apalutamide
Keep reading about Buprenorphine
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