Rilzabrutinib and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rilzabrutinib
Simvastatin
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's talk about taking rilzabrutinib (Wayrilz) and simvastatin (Zocor) together. Your body clears simvastatin using a liver enzyme called CYP3A. Rilzabrutinib slows that enzyme down, so simvastatin can build up higher than usual in your blood.
When there's more simvastatin around, the main worry is muscle-related side effects, like unusual aches, soreness, or weakness. This is expected based on how the drugs work, not from lots of real-world reports yet. The good news is this is very manageable. Your care team can watch you a little more closely and adjust your simvastatin dose if needed. Please don't stop either medicine on your own, just check in with your pharmacist or doctor.
Mechanism: Rilzabrutinib is a moderate CYP3A inhibitor; simvastatin is a CYP3A substrate (and neither is a prodrug relevant here). Inhibition reduces simvastatin metabolism, raising its exposure.
Direction/magnitude: Increased simvastatin AUC/Cmax expected. Reference data: rilzabrutinib 400 mg raised midazolam Cmax and AUC ~2.2-fold (up to ~3.0-fold predicted with 400 mg BID). Elevated statin exposure increases myopathy/rhabdomyolysis risk.
- Onset: unspecified
- Evidence: theoretical/predicted
- Management: monitor for statin-related adverse effects (myalgia, weakness, dark urine); consider simvastatin dose adjustment individualized by the team; check CK if symptomatic.
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 can rise, raising the likelihood of adverse reactions attributable 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
This interaction is manageable, and you should keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may monitor you more closely for statin side effects and may adjust your simvastatin dose so it is individualized to you.
- Watch for muscle pain, tenderness, or weakness, especially if it is unexplained or comes with dark-colored urine, and report these promptly.
- Bring a full medication list (including over-the-counter products) to your pharmacist or doctor so they can review it.
Raise any new symptoms with your pharmacist or prescriber rather than changing doses yourself.
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 as much as 3.0-fold when coadministered with rilzabrutinib 400 mg twice daily 1.
Common questions
Can I take Rilzabrutinib and Simvastatin together?
Rilzabrutinib can raise simvastatin levels by slowing its breakdown, which may increase the chance of muscle-related side effects. Keep taking both as prescribed and let your care team monitor you and adjust the simvastatin dose if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rilzabrutinib and Simvastatin 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 Simvastatin interaction managed?
This interaction is manageable, and you should keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may monitor you more closely for statin side effects and may adjust your simvastatin dose so it is individualized to you. Watch for muscle pain, tenderness, or weakness, especially if it is unexplained or comes with dark-colored urine, and repor… 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 Simvastatin 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 Simvastatin
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