Simvastatin and Mifepristone: 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
Mifepristone
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.
These two medicines should not be taken together. Mifepristone slows down the liver enzyme that normally breaks down simvastatin. When that clean-up is blocked, simvastatin builds up in your body, and the amount in your blood can climb about 10 times higher than normal.
That extra simvastatin raises the risk of a serious muscle problem. Signs include unexplained muscle pain, tenderness, or weakness, and in rare cases muscle breakdown that can harm the kidneys. The good news: your care team can manage cholesterol safely with a different plan. Please talk with your pharmacist or doctor before taking both, and never stop either one on your own.
Contraindicated combination. Mifepristone is a potent CYP3A inhibitor; simvastatin is a CYP3A substrate (its lactone is hydrolyzed to the active acid, but both are CYP3A-metabolized). Inhibition markedly reduces simvastatin clearance.
- Direction/magnitude: increased exposure; AUC ratio ~10.4 (simvastatin) and ~15.7 (simvastatin acid).
- Risk: dose-dependent myopathy and rhabdomyolysis.
- Evidence: probable, human PK data.
- Management: avoid coadministration. Because of mifepristone's long terminal half-life at steady state, wait at least 2 weeks after stopping mifepristone before starting simvastatin. Monitor for muscle symptoms/CK if exposure occurred.
What happens
Increased simvastatin exposure and an increased risk of myopathy and rhabdomyolysis
Interaction Deep Dive
As a CYP3A inhibitor, miFEPRIStone has been shown to markedly raise simvastatin plasma levels in healthy volunteers. Giving miFEPRIStone together with simvastatin is contraindicated, since the resulting rise in simvastatin exposure can heighten the likelihood of serious adverse effects, including myopathy and rhabdomyolysis. When simvastatin (itself a CYP3A substrate) was administered alongside miFEPRIStone, the mean AUC ratios (with versus without) reached 10.4 for simvastatin and 15.7 for simvastatin acid, relative to simvastatin exposure given alone. Because miFEPRIStone has a long terminal half-life at steady state, a minimum of 2 weeks should elapse after discontinuing miFEPRIStone before starting simvastatin1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of simvastatin
How to manage this interaction
These drugs are not meant to be used together. Because mifepristone can push simvastatin levels far higher, your care team will avoid this combination and choose a safer option.
- Keep taking your medicines as prescribed, and do not stop either one on your own.
- Ask your pharmacist or prescriber whether a different cholesterol medicine is a better fit while you are on mifepristone.
- If you have recently stopped mifepristone, your team will typically wait at least 2 weeks before starting simvastatin, since mifepristone stays in the body a long time.
- Report any unexplained muscle pain, weakness, or dark urine right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a pharmacokinetic study, giving miFEPRIStone 1200 mg once daily for 10 days together with a single 80-mg dose of simvastatin in healthy subjects markedly raised the exposure and plasma concentrations of both simvastatin and simvastatin acid. Relative to simvastatin given alone, coadministration with miFEPRIStone produced mean AUC and Cmax ratios of 15.7 and 18.2, respectively, for simvastatin acid, and 10.4 and 7.02, respectively, for simvastatin 1.
Common questions
Can I take Simvastatin and Mifepristone together?
Do not take mifepristone and simvastatin together, since mifepristone can raise simvastatin levels about tenfold and greatly increase the risk of serious muscle damage. If you have stopped mifepristone, wait at least 2 weeks before starting simvastatin, and ask your care team about a safer cholesterol option. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Mifepristone interaction?
It is rated contraindicated. These should generally not be used together.
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 Mifepristone interaction managed?
These drugs are not meant to be used together. Because mifepristone can push simvastatin levels far higher, your care team will avoid this combination and choose a safer option. Keep taking your medicines as prescribed, and do not stop either one on your own. Ask your pharmacist or prescriber whether a different cholesterol medicine is a better fit while you are on mifepristone. If you have recent… 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 Simvastatin or Mifepristone 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: KORLYM(R) oral tablets, mifepristone oral tablets. Corcept Therapeutics Incorporated (per Dailmed), Redwood City, CA, 2024. DailyMed
Keep reading about Mifepristone
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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