Phenprocoumon and Mercaptopurine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mercaptopurine
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.
What happens
Reduced phenprocoumon efficacy
Interaction Deep Dive
Two patients who experienced a decrease in their international normalized ratio (INR) when azathioprine was added to phenprocoumon therapy have been described1. Possible mechanisms for this interaction include induction of phenprocoumon metabolism, decreased gastrointestinal absorption of phenprocoumon, and an increase in prothrombin synthesis.
Why it happens (mechanism)
Unknown
Literature reports
1 report — tap to read
a) Two case reports describe a decrease in phenprocoumon efficacy when azathioprine was added to therapy. Both patients had systemic lupus erythematosus (SLE). Patient 1, a 19-year-old female, received phenprocoumon as prophylaxis against thromboses. Cyclophosphamide treatment was replaced by azathioprine 100 mg daily, and the international normalized ratio (INR) decreased from 2.5 to 1.1 four weeks after azathioprine was initiated. The phenprocoumon dose was increased from an average of 2.35 mg daily to 4.5 mg daily to maintain the INR in a therapeutic range (2.0-3.0). Patient 2, a 49-year-old female, was stabilized on phenprocoumon when her cyclophosphamide treatment was also changed to azathioprine 100 mg daily. Her INR decreased from 2.4 to 1.2 during the first six weeks of concomitant therapy. The average phenprocoumon dose was increased from 3.32 mg daily to 5.79 mg daily to return the INR to 2.0 1.
Common questions
Can I take Phenprocoumon and Mercaptopurine together?
Reduced phenprocoumon efficacy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenprocoumon and Mercaptopurine interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Phenprocoumon or Mercaptopurine 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 anything you'd monitor while I'm on both?
References (1)
- Jeppesen U, Rasmussen JM, & Brosen K: Clinically important interaction between azathioprine (Imurel) and phenprocoumon (Marcoumar) (letter). Eur J Clin Pharmacol 1997; 52:503-504. PubMed
Keep reading about Mercaptopurine
Keep reading about Phenprocoumon
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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