Simvastatin and Mibefradil: 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
Simvastatin
Mibefradil
No brand names on record
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. Simvastatin (Zocor) is a cholesterol medicine that your body clears using a liver enzyme called CYP3A4. Mibefradil strongly blocks that enzyme. When the enzyme is blocked, simvastatin builds up to higher levels than it should.
Too much simvastatin can cause muscle problems. This can range from muscle aches to a rare but serious condition called rhabdomyolysis, where muscle tissue breaks down and can harm the kidneys. The good news is this is easy to avoid. Never combine these two, and always talk with your pharmacist or doctor before starting any new medicine.
Contraindicated combination. Simvastatin undergoes extensive CYP3A4-mediated metabolism. Mibefradil is a potent CYP3A4 inhibitor, so co-administration markedly increases simvastatin systemic exposure (AUC/Cmax).
- Effect: elevated risk of myopathy and rhabdomyolysis (dose-dependent statin toxicity).
- Direction: increased simvastatin effect and toxicity (neither drug is a prodrug requiring activation).
- Onset: delayed.
- Evidence: probable.
- Management: concurrent use is contraindicated; do not combine. If a CYP3A4 inhibitor is required, an alternative lipid-lowering agent less dependent on CYP3A4 should be considered by the prescriber.
What happens
An increased risk of myopathy and/or rhabdomyolysis
Interaction Deep Dive
Cases of myopathy and rhabdomyolysis have been reported both when simvastatin is used by itself and when it is given together with mibefradil. Because the metabolic clearance of simvastatin relies on CYP450 3A4, and mibefradil acts as a strong inhibitor of that same enzyme, using simvastatin and mibefradil at the same time is contraindicated34.
Why it happens (mechanism)
Inhibition of cytochrome P450 3A4-mediated simvastatin metabolism by mibefradil
How to manage this interaction
The key step here is simple: these two are not used together.
- Do not take simvastatin and mibefradil at the same time. This combination is contraindicated.
- Keep taking your prescribed medicines, but let your pharmacist and prescriber know your full medication list so they can confirm you are not on both.
- Your care team may choose a different cholesterol medicine or a different alternative agent so you can be treated safely.
- Report any unexplained muscle pain, tenderness, weakness, or dark-colored urine to your prescriber right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) An 83-year-old woman was hospitalized one week after developing an immobilizing myopathy accompanied by low-back pain and oliguria. Before admission, she had been maintained on simvastatin 20 mg once daily for one year, and mibefradil 50 mg daily had been added four weeks before admission to manage her blood pressure. At admission, her creatine phosphokinase (CPK) measured 50125 U/L, her alanine aminotransferase was 1179 U/L, and her aspartate aminotransferase was 998 U/L. She was also hyperkalemic and had severe renal failure. Rhabdomyolysis was diagnosed, and all of her medications were stopped. Over the next 10 days, she recovered the use of her legs and her muscle pain resolved. She was discharged in good physical condition four weeks after admission 1.
b) A 47-year-old man who had received a kidney transplant and was being treated with simvastatin 40 mg daily and cyclosporine for two weeks developed rhabdomyolysis one month after mibefradil 50 mg daily was added to his regimen. He was admitted after reporting progressive muscle weakness, myalgia, hematuria, and oliguria. His laboratory values on admission included CPK 150,698 U/L, LDH 2986 U/L, creatinine 4.8 mg/dL, and SGOT 3101 U/L. At admission, his simvastatin concentration was measured at 135 ngEq/mL. Four days afterward, the simvastatin level remained detectable at 6.4 ngEq/mL. The plasma half-life of simvastatin acid is under two hours, and chronic therapy does not lead to accumulation of simvastatin or simvastatin acid. This patient's rhabdomyolysis was attributed to mibefradil's inhibition of the cytochrome P450 3A4-mediated metabolism of cyclosporine and simvastatin 2.
Common questions
Can I take Simvastatin and Mibefradil together?
Simvastatin and mibefradil should not be taken together because mibefradil blocks the enzyme that clears simvastatin, raising the risk of serious muscle breakdown. Ask your pharmacist or doctor to pick a safer alternative. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Mibefradil interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How is the Simvastatin and Mibefradil interaction managed?
The key step here is simple: these two are not used together. Do not take simvastatin and mibefradil at the same time. This combination is contraindicated. Keep taking your prescribed medicines, but let your pharmacist and prescriber know your full medication list so they can confirm you are not on both. Your care team may choose a different cholesterol medicine or a different alternative agent so… 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 Mibefradil 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 (4)
- Schmassmann-Suhijar D, Bullingham R, Gasser R, et al: Rhabdomyolysis due to interaction of simvastatin and mibefradil. Lancet 1998; 351:1929-1930.
- Wombolt DG, Jackson A, Punn R, et al: Case report: rhabdomyolysis induced by mibefradil in a patient treated with cyclosporine and simvastatin. J Clin Pharmacol 1999; 39:310-312. DOI
- Product Information: Posicor(R), mibefradil dihydrochloride. Roche Laboratories Inc. Nutley, NJ, 1997.
- Product Information: Zocor(R), simvastatin. Merck & Co. Inc. West Point, PA, 1998. DailyMed
Keep reading about Simvastatin
Keep reading about Mibefradil
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