Simvastatin and Duvelisib: 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
Duvelisib
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.
Duvelisib (Copiktra) can raise the level of simvastatin (Zocor) in your body. Duvelisib slows down a liver enzyme called CYP3A4 that normally breaks simvastatin down. With that enzyme working slower, simvastatin can build up higher than intended.
Higher statin levels can raise the chance of muscle side effects, like unusual muscle aches, tenderness, or weakness, and in rare cases liver strain. The good news is your care team can manage this easily. They may adjust your simvastatin dose and keep a closer eye on you. If you notice new muscle pain or weakness, let your pharmacist or doctor know.
Mechanism: Duvelisib inhibits CYP3A4; simvastatin is a sensitive CYP3A4 substrate. Expected effect is increased simvastatin exposure (higher AUC/Cmax) and elevated risk of dose-dependent toxicity, notably myopathy/rhabdomyolysis and hepatotoxicity.
- Direction: increased simvastatin effect/toxicity (neither drug is a prodrug here).
- Evidence: theoretical; extrapolated from duvelisib increasing midazolam AUC/Cmax.
- Onset: unspecified.
- Management: consider reducing the simvastatin dose; monitor for muscle symptoms and check CK/LFTs if indicated. Dose should be individualized by the care team.
What happens
Increased exposure of sensitive CYP3A4 substrates and risk of toxicity
Interaction Deep Dive
Giving duvelisib, which inhibits CYP3A4, alongside a CYP3A4 substrate raises the exposure of sensitive substrates, potentially heightening the likelihood of toxicities from those agents. Combining duvelisib with midazolam (a sensitive CYP3A4 substrate) produced an increase in both the AUC and Cmax of midazolam. It is advisable to lower the dose of the sensitive CYP3A4 substrate and watch for indications of toxicity from the coadministered sensitive CYP3A substrate1.
Why it happens (mechanism)
Inhibition of CYP3A4 substrate metabolism by duvelisib
How to manage this interaction
This is manageable with dose tailoring and monitoring. Keep taking both medications as prescribed unless your care team tells you otherwise.
- Your team may reduce your simvastatin dose and adjust it to fit your situation.
- They may monitor you more closely for signs of statin toxicity.
- Report new or unexplained muscle pain, tenderness, weakness, or dark urine, or any signs of liver trouble, to your pharmacist or doctor promptly.
- Ask your pharmacist before starting any new medicine, since other CYP3A4 interactions can add up.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) When duvelisib 25 mg was given twice daily for 5 days together with a single oral 2-mg dose of midazolam (a sensitive CYP3A4 substrate), the midazolam AUC rose 4.3-fold and the Cmax rose 2.2-fold in healthy adults 2.
Common questions
Can I take Simvastatin and Duvelisib together?
Duvelisib can raise simvastatin levels and increase the risk of muscle and liver side effects; your care team may lower the simvastatin dose and watch you more closely, so report any muscle pain or weakness. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Duvelisib 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 Simvastatin and Duvelisib interaction managed?
This is manageable with dose tailoring and monitoring. Keep taking both medications as prescribed unless your care team tells you otherwise. Your team may reduce your simvastatin dose and adjust it to fit your situation. They may monitor you more closely for signs of statin toxicity. Report new or unexplained muscle pain, tenderness, weakness, or dark urine, or any signs of liver trouble, to your… 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 Simvastatin or Duvelisib 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)
Keep reading about Duvelisib
Keep reading about Simvastatin
These medications also interact with supplements
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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