Buprenorphine and Rilzabrutinib: 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
Rilzabrutinib
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.
Here's what's going on. Buprenorphine is a strong pain and opioid-dependence medicine. Your body clears it partly through a liver enzyme called CYP3A. Rilzabrutinib can slow that enzyme down, so more buprenorphine may stay in your system than usual.
That could make buprenorphine's effects stronger, like extra drowsiness, dizziness, nausea, or slower breathing. This is based mostly on how the drugs are expected to behave, not on lots of real-world reports, so it's a caution rather than an alarm. Please don't change anything on your own. Your care team can watch you a little more closely and adjust your dose if needed.
Mechanism: Rilzabrutinib is a moderate CYP3A inhibitor; buprenorphine is a CYP3A4 substrate (active drug, not a prodrug). Inhibition reduces buprenorphine metabolism, increasing its exposure and opioid-related adverse effects.
- Direction: Increased buprenorphine effect.
- Magnitude: Not specific to buprenorphine; rilzabrutinib raised midazolam Cmax/AUC ~2.2-fold single dose, predicted up to 3.0-fold at 400 mg BID.
- Evidence: Theoretical for this pair; extrapolated from midazolam data.
- Onset: Unspecified.
- Management: Monitor for sedation, respiratory depression, nausea; consider buprenorphine dose adjustment individualized by the team.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions
Interaction Deep Dive
When rilzabrutinib (a moderate inhibitor of CYP3A) is given together with CYP3A substrates, the exposure to those substrates may rise, heightening the likelihood of adverse reactions linked to them. Watch more closely for adverse reactions associated with the co-administered CYP3A substrate and adjust its dosage as appropriate. A drug interaction study in healthy participants showed that taking a single 400 mg dose of rilzabrutinib alongside midazolam (a sensitive CYP3A substrate) raised both the Cmax and AUC of midazolam by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise by as much as 3.0-fold when co-administered with rilzabrutinib 400 mg twice daily1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by rilzabrutinib
How to manage this interaction
The good news is this is manageable. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your team may monitor you more closely for stronger opioid effects such as extra drowsiness, dizziness, nausea, confusion, or slowed breathing.
- Your buprenorphine dose may need to be adjusted and individualized by your care team.
- Tell your pharmacist or doctor promptly if you feel unusually sleepy or foggy, or notice breathing changes.
- Make sure both prescribers know you take these together, especially when starting or stopping either one.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study involving healthy volunteers, giving a single 400 mg dose of rilzabrutinib together with midazolam (a sensitive CYP3A substrate) raised the Cmax and AUC of midazolam by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise by up to 3.0-fold when coadministered with 400 mg rilzabrutinib twice daily 1.
Common questions
Can I take Buprenorphine and Rilzabrutinib together?
Rilzabrutinib can slow how your body breaks down buprenorphine, so buprenorphine's effects may be stronger. This is a theoretical caution; keep taking both as prescribed and let your care team monitor you and adjust the dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Rilzabrutinib interaction?
It is rated moderate. Can be significant — usually manageable with 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 Rilzabrutinib interaction managed?
The good news is this is manageable. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your team may monitor you more closely for stronger opioid effects such as extra drowsiness, dizziness, nausea, confusion, or slowed breathing. Your buprenorphine dose may need to be adjusted and individualized by your care team. Tell your pharmacist or doctor promptly… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Buprenorphine or Rilzabrutinib 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: WAYRILZ™ oral tablets, rilzabrutinib oral tablets. Genzyme Corporation (per FDA), Cambridge, MA, 2025. DailyMed
Keep reading about Buprenorphine
Keep reading about Rilzabrutinib
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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