Apalutamide 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
Apalutamide
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.
Here's what's going on. Apalutamide (Erleada) speeds up the way your body breaks down and clears out simvastatin (Zocor). That means less simvastatin stays in your system, so it may not lower your cholesterol as well as it should.
The good news is this is manageable. Please keep taking both medicines as prescribed, and don't stop anything on your own. Your care team can check your cholesterol numbers and, if needed, adjust your statin dose or consider another option. If you have questions, your pharmacist or doctor is happy to walk you through it.
Effect: Apalutamide reduces simvastatin exposure via induction of CYP3A4 metabolism and of OATP1B1- and BCRP-mediated efflux transport. Neither agent is affected as a prodrug here, so lower simvastatin exposure translates directly to reduced lipid-lowering efficacy.
- Direction: decreased simvastatin AUC/Cmax, potential loss of effect
- Magnitude reference: apalutamide decreased rosuvastatin AUC ~41% and midazolam AUC ~92%
- Evidence: probable; severity: major; onset unspecified
- Management: monitor lipid panel; evaluate for loss of statin efficacy; dose may need individualized titration or an alternative agent per the care team
What happens
Reduced simvastatin exposure
Interaction Deep Dive
Exercise caution when apalutamide is given alongside simvastatin (a substrate of CYP3A4, OATP1B1, and BCRP), as this combination may likewise lower simvastatin exposure. When apalutamide was administered together with single oral doses of transporter substrates, the AUC of rosuvastatin (a BCRP/OATP1B1 substrate) fell by 41%. Administering a single apalutamide dose with the CYP3A4 substrate midazolam produced a 92% reduction in the midazolam AUC. If the medication is maintained, assess for any loss of activity1.
Why it happens (mechanism)
Induction of OATP1B1-mediated efflux transport of simvastatin; induction of BCRP-mediated efflux transport of simvastatin; induction of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
What your care team may do:
- Check your cholesterol (lipid panel) to see whether the statin is still working well while you take both drugs.
- Adjust and individualize your simvastatin dose if needed, or consider a different cholesterol medicine.
- Monitor you more closely as long as the two are used together.
What you should do:
- Keep taking both medicines exactly as prescribed. Do not stop or change doses on your own.
- Ask your pharmacist or prescriber to confirm your cholesterol goals are still being met, and mention any new symptoms or concerns.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Giving apalutamide together with single oral doses of transporter substrates produced a 41% reduction in the AUC of rosuvastatin (a BCRP/OATP1B1 substrate) 1.
b) Administering a single dose of apalutamide alongside midazolam, a CYP3A4 substrate, produced a 92% reduction in the AUC of midazolam 1.
Common questions
Can I take Apalutamide and Simvastatin together?
Apalutamide can lower simvastatin levels and make it less effective at controlling cholesterol, so keep taking both as prescribed and let your care team monitor your lipids and adjust treatment if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Apalutamide and Simvastatin 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 Simvastatin interaction managed?
What your care team may do: Check your cholesterol (lipid panel) to see whether the statin is still working well while you take both drugs. Adjust and individualize your simvastatin dose if needed, or consider a different cholesterol medicine. Monitor you more closely as long as the two are used together. What you should do: Keep taking both medicines exactly as prescribed. Do not stop or change d… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Apalutamide 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 a safer alternative to one of these medications for me?
References (1)
- Product Information: ERLEADA(R) oral tablets, apalutamide oral tablets. Janssen Products LP (per FDA), Horsham, PA, 2024. DailyMed
Keep reading about Apalutamide
Keep reading about Simvastatin
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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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