Verapamil 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
Verapamil
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.
Verapamil can raise the level of simvastatin in your body. Verapamil slows down the liver enzyme (called CYP3A4) that normally breaks simvastatin down. With that clean-up slowed, simvastatin builds up higher than usual. In one study, blood levels of simvastatin roughly doubled.
The main worry with too much simvastatin is muscle trouble, called myopathy. Watch for unexplained muscle pain, tenderness, or weakness, especially with dark urine. This is a well-known combination, and your care team can manage it easily, often by keeping your simvastatin dose low. Please talk with your pharmacist or doctor before making any changes, and tell them right away if your muscles start aching.
Mechanism: Verapamil inhibits CYP3A4, the primary enzyme metabolizing simvastatin (an active drug, not a prodrug in this context). Result is increased simvastatin exposure and elevated myopathy/rhabdomyolysis risk.
- Direction: Increased simvastatin effect and toxicity risk.
- Magnitude: Simvastatin AUC increased ~2.5x, acid metabolite ~2.3x; Cmax ~2.1x and ~2.4x respectively.
- Onset: Rapid. Evidence: Established.
- Management: Do not exceed simvastatin 10 mg daily with verapamil. Monitor for muscle pain/weakness and check CK if symptomatic. Discontinue if myopathy is diagnosed or suspected. Consider a non-CYP3A4 statin (e.g., pravastatin, rosuvastatin) if higher LDL-lowering is needed.
What happens
Increased simvastatin exposure and an increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
Taking verapamil at the same time as simvastatin raises simvastatin exposure and can heighten the likelihood of myopathy or rhabdomyolysis. When the two must be given together, simvastatin should be limited to no more than 10 mg per day. Should myopathy be diagnosed or suspected, the drug should be stopped1. A drug interaction study administered a single 20 mg dose of simvastatin along with verapamil dosed at 240 mg once daily on days 1 through 7 and then 240 mg twice daily on days 8 through 10; this produced increases in the AUC of simvastatin and simvastatin acid of 2.5 and 2.3, respectively, and increases in Cmax of 2.1 and 2.4, respectively 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism by simvastatin
How to manage this interaction
This combination is used, but it is dosed carefully. Keep taking both medications as prescribed unless your care team tells you otherwise.
- Your prescriber will typically keep simvastatin at a low dose (no more than 10 mg daily) while you are also taking verapamil.
- Your team may monitor you more closely and can individualize your statin choice or dose.
- Report any muscle pain, tenderness, weakness, or dark-colored urine to your pharmacist or doctor promptly, since these can signal muscle injury.
- Do not start, stop, or change either drug on your own. Ask your pharmacist if you are unsure about your current dose.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) In a pharmacokinetic study, the simvastatin AUC rose by as much as 2.5 times when simvastatin and verapamil were given together. Participants took verapamil sustained-release 240 mg once daily on days 1 through 7, then 240 mg twice daily on days 8 through 10, and on day 10 a single 80-mg dose of simvastatin was given. For simvastatin, the mean ratio (with verapamil versus without verapamil) was 2.5 for AUC and 2.1 for Cmax. The corresponding ratios for simvastatin acid (the beta-hydroxyacid of simvastatin) were 2.3 for AUC and 2.4 for Cmax 1.
b) In a randomized, double-blind crossover study, 12 young healthy volunteers took either erythromycin 500 mg three times daily, verapamil 80 mg three times daily, or placebo over two days. On day 2, simvastatin 40 mg was also given. In the presence of verapamil, the simvastatin maximum concentration (Cmax) rose from 10.5 ng/mL to 36.9 ng/mL (25.1 nanomol/L to 88.2 nanomol/L) and the area under the concentration-time curve (AUC) from 0 to 24 hours increased from 17.7 ng/mL/hr to 82.3 ng/mL/hr 3.
c) In a drug interaction study, giving a single 20-mg dose of simvastatin along with verapamil 240 mg once daily on days 1 to 7 and then 240 mg twice daily on days 8 to 10 led to increases in simvastatin and simvastatin acid AUC of 2.5 fold and 2.3 fold, and Cmax of 2.1 fold and 2.4 fold, respectively 2.
Common questions
Can I take Verapamil and Simvastatin together?
Verapamil raises simvastatin levels and muscle-injury risk, so simvastatin is usually capped at 10 mg daily when the two are taken together. Report any muscle pain or weakness to your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Verapamil 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Verapamil and Simvastatin interaction managed?
This combination is used, but it is dosed carefully. Keep taking both medications as prescribed unless your care team tells you otherwise. Your prescriber will typically keep simvastatin at a low dose (no more than 10 mg daily) while you are also taking verapamil. Your team may monitor you more closely and can individualize your statin choice or dose. Report any muscle pain, tenderness, weakness,… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Verapamil 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 (3)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2024. DailyMed
- Kantola T, Kivisto KT, & Neuvonen PJ: Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 1998; 64:177-182. DOI
Keep reading about Verapamil
Keep reading about Simvastatin
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