Rilzabrutinib and Clindamycin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rilzabrutinib
Clindamycin
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.
You've been prescribed two medicines that can interact. Rilzabrutinib (Wayrilz) can slow down a liver enzyme (called CYP3A) that helps your body break down clindamycin. When that enzyme is slowed, more clindamycin can build up in your body, which may make its side effects (like stomach upset, nausea, or diarrhea) a bit more likely.
This concern is based mostly on lab and study predictions, not many real-world reports, so it's usually manageable. Keep taking both as prescribed, and let your pharmacist or doctor know if you notice new or stronger side effects. Your care team can watch you a little more closely or adjust your dose if needed.
Mechanism: Rilzabrutinib is a moderate CYP3A inhibitor. Clindamycin is metabolized largely by CYP3A4 (to N-demethyl and sulfoxide metabolites). Inhibition may reduce clindamycin clearance, increasing exposure (AUC/Cmax) and the risk of substrate-related adverse effects.
- Direction: increased clindamycin exposure.
- Magnitude: not specific to clindamycin; with midazolam (sensitive substrate), rilzabrutinib 400 mg raised Cmax and AUC ~2.2-fold, with predicted increases up to 3.0-fold on twice-daily dosing.
- Onset: unspecified. Evidence: theoretical.
- Management: monitor for clindamycin adverse effects (GI intolerance, diarrhea) more frequently; adjust dose as clinically indicated.
What happens
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions
Interaction Deep Dive
When rilzabrutinib, a moderate CYP3A inhibitor, is given together with CYP3A substrates, exposure to those substrates may rise, raising the likelihood of adverse reactions tied to them. Watch more closely for adverse reactions from the co-administered CYP3A substrate and consider adjusting its dose as needed. A drug interaction study in healthy participants showed that giving a single 400 mg dose of rilzabrutinib alongside midazolam (a sensitive CYP3A substrate) raised midazolam Cmax and AUC by 2.2-fold. In patients with immune thrombocytopenia, midazolam AUC is projected to rise 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 a manageable situation. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely for clindamycin side effects such as nausea, stomach cramps, or diarrhea.
- Your clindamycin dose may be adjusted and individualized by your team if needed.
- Report any persistent or severe diarrhea promptly, since this can matter with clindamycin.
Check with your pharmacist or doctor before starting or stopping either medicine, and mention all other medicines you take so they can review them too.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study conducted in 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 combined with 400 mg rilzabrutinib administered twice daily 1.
Common questions
Can I take Rilzabrutinib and Clindamycin together?
Rilzabrutinib can raise clindamycin levels by slowing its breakdown, so watch for more stomach and gut side effects and let your care team know if they appear; they can monitor you or adjust the dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rilzabrutinib and Clindamycin 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 Rilzabrutinib and Clindamycin interaction managed?
The good news is this is a manageable situation. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely for clindamycin side effects such as nausea, stomach cramps, or diarrhea. Your clindamycin dose may be adjusted and individualized by your team if needed. Report any persistent or severe diarrhea promptly, since th… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Rilzabrutinib or Clindamycin 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 Rilzabrutinib
Keep reading about Clindamycin
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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