Simvastatin and Phenprocoumon: 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
Phenprocoumon
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.
You've been prescribed simvastatin (a cholesterol medicine) along with phenprocoumon, which is a blood thinner in the same family as warfarin. When these two are taken together, the blood thinner can become a little stronger than expected. Doctors track blood thinners with a test called the INR, and this combination can push that number up, which means a higher chance of bleeding or bruising.
The good news is that this is very manageable. Your care team simply checks your INR more often when simvastatin is started, changed, or stopped, and adjusts your dose as needed. Watch for unusual bruising, nosebleeds, or blood in your urine or stool, and let your doctor know if you see anything.
Effect: Concurrent simvastatin and phenprocoumon (a coumarin anticoagulant) may potentiate anticoagulant effect, increasing INR and bleeding risk.
Mechanism: Additive effects on hemostasis (pharmacodynamic). Neither agent requires the other for activation, so the direction is increased anticoagulant effect.
- Direction: Increased phenprocoumon effect / elevated INR
- Onset: Delayed
- Evidence: Probable
- Severity: Major (phenprocoumon is narrow therapeutic index)
Management: Obtain baseline INR before starting simvastatin, then monitor frequently after initiation, dose titration, or discontinuation. Once stable, resume routine INR intervals. Titrate anticoagulant dose individually to target INR.
What happens
Increased risk of bleeding, increased INR and potentiated effect of coumarin anticoagulants
Interaction Deep Dive
Taking simvastatin together with coumarin anticoagulants such as phenprocoumon can raise the INR. For patients on coumarin anticoagulants, check the INR prior to beginning simvastatin, and repeat testing often enough following the start of therapy, any dose adjustment, or withdrawal to confirm that the INR does not change significantly. After the INR has stabilized, continue monitoring it at the standard recommended intervals12.
Why it happens (mechanism)
Additive effects on hemostasis
How to manage this interaction
Keep taking both medications as prescribed unless your doctor or pharmacist tells you otherwise. This combination is used safely all the time with proper monitoring.
- Your team will typically check your INR before starting simvastatin, then check it more often after starting, changing, or stopping it.
- Once your INR is stable, testing goes back to your usual schedule.
- Your blood thinner dose may need to be adjusted and individualized by your care team based on those results.
- Report any unusual bruising, bleeding gums, nosebleeds, or dark/bloody stools or urine promptly.
Ask your pharmacist to confirm your INR check-in plan whenever your simvastatin changes.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) Across 2 clinical trials, one enrolling patients with hypercholesterolemia and the other involving healthy volunteers, simvastatin at 20 to 40 mg per day enhanced the action of coumarin anticoagulants; the INR rose from a starting value of 1.7 to 1.8 in the volunteer study and from 2.6 to 3.4 in the patient study 12.
b) Giving simvastatin together with warfarin caused marked elevations in the international normalized ratio (INR) values of patients who had previously been maintained on stable warfarin doses. In a cohort study, patients (n=29) whose warfarin dose requirements had been stable for at least 3 preceding clinic visits (with the time frame not specified) were assessed for INR changes after starting concurrent simvastatin. INR values were documented immediately before simvastatin was begun and at the clinic visit right after simvastatin was started, and the daily warfarin dose requirement was tracked until a stable requirement was reached over 3 consecutive clinic visits. Following the initiation of simvastatin, mean INR values (baseline of 2.5) rose by 27% (to 3.15) and the mean required warfarin dose fell by 9% (from 4.2 milligrams (mg) to 3.8 mg daily) 3.
c) A 61-year-old man who had been on warfarin therapy for five years was begun on simvastatin for hypercholesterolemia. Four months afterward he sustained a minor head injury, and two weeks later he reported a severe headache and neck stiffness. An MRI showed bilateral subdural hematoma. The hematoma was ascribed to the heightened anticoagulant effect of warfarin brought about by simvastatin 4.
d) An 82-year-old male patient was admitted to the hospital reporting bilateral lower extremity muscle pain and weakness lasting seven days. He had been maintained on furosemide, digoxin, potassium, and simvastatin 20 mg daily for the prior 18 months. One week before admission, warfarin 5 mg daily had been started for deep venous thrombosis. Laboratory findings at admission showed acute renal failure (serum creatinine 3.4 mg/dL [301 mcmol/L]), hyperkalemia (8.2 mEq/L [8.2 mmol/L]), a raised international normalized ratio (4.3), and a serum creatine phosphokinase of 785 U/L. Simvastatin was stopped while his renal failure and hyperkalemia were managed appropriately, and the laboratory abnormalities and symptoms resolved within five days. Because this patient's symptoms cleared after simvastatin was discontinued, the acute renal failure and rhabdomyolysis were attributed to an interaction between warfarin and simvastatin, possibly owing to competition for cytochrome P450 3A4-mediated metabolism 5.
e) A case report described a considerable rise in INR 4 weeks after switching from oral atorvastatin 10 mg once daily to oral simvastatin 10 mg once daily in an 82-year-old Caucasian woman. The patient had been stable on 2.5 mg of oral warfarin for 2 years before the event (therapeutic INR range, 2.0 to 3.5) and had been on warfarin for 30 years because of several episodes of deep venous thrombosis and one episode of lung embolism. A routine anticoagulant follow-up visit 4 weeks after she began simvastatin found her INR above the detection range of the equipment (greater than 8). The patient denied taking any extra medications and stated she was adherent to her warfarin regimen. Her comorbidities included polycythemia, intermittent claudication, migraines, gout, glaucoma, and hypertension. Her hypertension was untreated because of a history of syncope while taking antihypertensives. Her only other medication was oral aspirin 75 mg/day for 9 years due to an episode of transient ischemic attack and a cerebral infarction. Her reported blood pressure (BP) at presentation was 198/118 millimeters of Mercury (mmHg). She was administered 5 mg of oral vitamin K and placed on bed rest. A few hours later the patient experienced a left cerebral hemorrhage with a reported systolic BP of 220 mg Hg and died shortly afterward. The Naranjo probability scale indicated the reaction was probably caused by a warfarin-simvastatin interaction. Among the possible mechanisms, it was suggested that simvastatin adversely affected the metabolism of warfarin, as well as this patient's unique sensitivity to changes in warfarin metabolism (as shown by her very low warfarin dose) 6.
Common questions
Can I take Simvastatin and Phenprocoumon together?
Simvastatin can strengthen phenprocoumon's blood-thinning effect and raise your INR, so your care team should check your INR more closely when simvastatin is started, changed, or stopped and adjust your dose as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Phenprocoumon 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 Simvastatin and Phenprocoumon interaction managed?
Keep taking both medications as prescribed unless your doctor or pharmacist tells you otherwise. This combination is used safely all the time with proper monitoring. Your team will typically check your INR before starting simvastatin, then check it more often after starting, changing, or stopping it. Once your INR is stable, testing goes back to your usual schedule. Your blood thinner dose may nee… 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 Phenprocoumon 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 (6)
- 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
- Hickmott H, Wynne H, & Kamali F: The effect of simvastatin co-medication on warfarin anticoagulation response and dose requirements (letter). Thromb Haemost 2003; 89:949-950. DOI
- Rise IR: Bilateral subdural hematoma caused by simvastatin during warfarin treatment. Case report. Acta Neurol Scand 1997; 96:339.
- Mogyorosi A, Bradley B, Showalter A, et al: Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin. J Intern Med 1999; 246:559-602. PubMed
- Westergren T, Johansson P, & Molden E: Probable Warfarin-Simvastatin Interaction (July/August). Ann Pharmacother 2007; -(-):---. PubMed
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Keep reading about Phenprocoumon
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