Drug Interaction Report

Acenocoumarol 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

Acenocoumarol

No brand names on record
+

Simvastatin

Flolipid Flolipid® Zocor Zocor®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Jul 4, 2026
LinkedIn
Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 95 documented Acenocoumarol interactions, 68 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
At a glance + Effects may be stronger
The Bottom Line
Simvastatin can strengthen acenocoumarol's blood-thinning effect and slightly raise the risk of a rare muscle problem, so your team will monitor your INR closely and adjust your dose. Keep taking both as prescribed and report unusual bleeding or muscle pain.

Taking these two together needs a little extra attention. Acenocoumarol is a blood thinner, and simvastatin is a cholesterol medicine. When used together, simvastatin can make your blood thinner work a bit stronger, which raises your risk of bleeding. There is also a small chance of a rare muscle problem called rhabdomyolysis, where muscles break down.

The good news is this is very manageable. Your care team can check your INR (a simple blood test for how thin your blood is) around the time simvastatin is started, changed, or stopped, and adjust your dose as needed. Keep taking both as prescribed, and let your team know about any unusual bruising, bleeding, or muscle pain or weakness.

Effect: Concurrent simvastatin and acenocoumarol may increase INR, raising bleeding risk; severe rhabdomyolysis has also been reported.

  • Direction: Enhanced anticoagulant effect of acenocoumarol (a narrow-therapeutic-index coumarin); increased myopathy risk.
  • Mechanism: Unknown/not fully characterized.
  • Onset: Delayed. Evidence: Probable. Severity: Major.
  • Management: Obtain baseline INR before initiating simvastatin, then monitor frequently after initiation, dose titration, or discontinuation until stable; resume routine INR intervals thereafter. Counsel on bleeding and myopathy signs (muscle pain, weakness, dark urine). Adjust acenocoumarol dose as guided by INR.
Onset
delayed
Evidence
probable
Severity
Major

What happens

An increased risk of bleeding and increased risk of rhabdomyolysis

Interaction Deep Dive

Taking simvastatin together with coumarin anticoagulants may raise the INR. For patients on coumarin anticoagulants, measure the INR prior to beginning simvastatin, and check it often enough following the start of therapy, any dose adjustment, or withdrawal to confirm that no meaningful change in INR develops. After the INR has stabilized, continue monitoring it at the usual recommended intervals1. Exercise caution when acenocoumarol and simvastatin are used together, since severe rhabdomyolysis has been reported 2.

Why it happens (mechanism)

Unknown

How to manage this interaction

Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This interaction is managed mainly by watching your INR closely.

  • Your team will typically check an INR before starting simvastatin, and then more often after it is started, changed, or stopped.
  • Your acenocoumarol dose may need to be adjusted and individualized based on those results, then monitored at regular intervals once stable.
  • Report any unusual bruising or bleeding, and any unexplained muscle pain, tenderness, weakness, or dark urine.

Ask your pharmacist or prescriber before making any changes.

Management is individual — confirm any change with your pharmacist or prescriber.

Literature reports

2 reports — tap to read

a) Across 2 clinical studies, one conducted in patients with hypercholesterolemia and the other in healthy volunteers, simvastatin 20 to 40 mg daily enhanced the action of coumarin anticoagulants; the INR rose from a baseline of 1.7 to 1.8 in the volunteer study and from 2.6 to 3.4 in the patient study 1.

b) A 69-year-old man taking simvastatin developed thigh muscle pain and weakness 3 weeks after starting acenocoumarol for a lung thromboembolism. His medical history included hypertension, peripheral vascular disease, diabetes mellitus, hypercholesterolemia, and heart allotransplant. Along with simvastatin, he was also taking diltiazem, repaglinide, cyclosporine, azathioprine, pentoxifylline, and pantoprazole, each of which he had used for an extended period without any dosage adjustments. Notable laboratory results included WBC 13,640/mm(3), creatinine 2.24 mg/dL (198 mcmol/L), and creatine kinase 29,674 Units/liter (U/L). Both acenocoumarol and simvastatin were stopped and intravenous fluids were given. By day 9, the muscle pain had fully resolved, and creatinine and creatine kinase had fallen to 1.38 mg/dL (122 mcmol/L) and 668 U/L, respectively 2.

Common questions

Can I take Acenocoumarol and Simvastatin together?

Simvastatin can strengthen acenocoumarol's blood-thinning effect and slightly raise the risk of a rare muscle problem, so your team will monitor your INR closely and adjust your dose. Keep taking both as prescribed and report unusual bleeding or muscle pain. Always confirm with your pharmacist or prescriber before making any change.

How serious is the Acenocoumarol 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 "delayed". Effects tend to build up gradually over days to weeks.

How is the Acenocoumarol and Simvastatin interaction managed?

Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This interaction is managed mainly by watching your INR closely. Your team will typically check an INR before starting simvastatin, and then more often after it is started, changed, or stopped. Your acenocoumarol dose may need to be adjusted and individualized based on those results, then monitored at regular inte… 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 Acenocoumarol 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 (2)

  1. Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
  2. Salinas A, Solis J, & Rico LA: Severe rhabdomyolysis secondary to simvastatin and acenocoumarol. Eur J Intern Med 2007; 18(2):165-165. PubMed
Was this write-up helpful?
Beyond drug–drug

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.

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist
This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.