Warfarin Drug Interactions

Aka: Warfarin Drug Interactions, Drug Interactions with Coumadin, Coumadin Drug Interactions

1. See Also
   1. Coumadin (Warfarin)
   2. Coumadin Protocol
   3. Coumadin Protocol for the Perioperative Period
2. Risk Factors: Drug Interaction with Warfarin
   1. Older age
   2. Acutely ill
   3. Dietary change
   4. Concurrent infection
3. Precautions
   1. Avoid using agents with major Drug Interactions with Warfarin
   2. When using medications known to affect INR, monitor INR closely
      1. Check INR 3-5 days after starting medication
      2. Check INR 3-5 days after stopping the medication
4. Drug Interactions: Agents that increase INR or bleeding risk
   1. Acetaminophen (Tylenol)
      1. Limit Acetaminophen dose to 2 grams per day for 7 days
      2. Consistent use of Acetaminophen may require more frequent monitoring of INR
   2. Alcohol
   3. Amiodarone (Cordarone)
      1. Precaution
         1. Amiodarone has a very long half-life and interaction persist for weeks after discontinuation
      2. Adjustment per Amiodarone maintenance dose
         1. Amiodarone 400 mg/day: Reduce Warfarin dose 40%
         2. Amiodarone 300 mg/day: Reduce Warfarin dose 35%
         3. Amiodarone 200 mg/day: Reduce Warfarin dose 30%
         4. Amiodarone 100 mg/day: Reduce Warfarin dose 25%
      3. Reference
         1. Sanoski (2002) Chest 121:19-23 [PubMed]
   4. Anabolic Steroids
   5. Antifungal Medications (Azoles)
      1. High risk Drug Interaction
         1. May significantly increase INR and bleeding risk
         2. Avoid if possible and if not, consider decreasing Warfarin dose by 25-30%
      2. Fluconazole (Diflucan)
      3. Ketoconazole (Nizoral)
      4. Itraconazole (Sporanox)
      5. Miconazole (Monistat)
   6. Aspirin and Salicylates
      1. Increased risk of gastric erosions and irritation with secondary Gastrointestinal Bleeding risk (as with NSAIDs)
      2. Platelet inhibition increases overall bleeding risk
      3. When required (e.g. Coronary Artery Disease, prior CVA), limit Aspirin dose to 81 mg orally daily
   7. Cephalosporins
      1. Cefoperazone (Cefobid)
      2. Cefamandole (Mandol)
      3. Cefotetan (Cefotan)
      4. Cefmetazole (Zefazone)
   8. Chloral Hydrate
   9. Cimetidine (Tagamet)
   10. Clofibrate
   11. Cranberry Juice (CYP2C9 inhibitor)
       1. Appears safe in at least one clinical trial
       2. Greenblatt (2006) Clin Pharmacol Ther 79:125-33 [PubMed]
   12. Danazol (Danocrine)
   13. Diflunisal (Dolobid)
   14. Diltiazem
   15. Disulfiram (Antabuse)
   16. Ginkgo Biloba (independent effect due to antiplatelet activity)
   17. Heparin
   18. HMG CoA Reductase inhibitors or Statins (via CYP2C9 inhibition)
       1. Highest risk: Fluvastatin, Lovastatin, Rosuvastatin, Simvastatin
       2. Lowest risk: Atorvastatin, Pravastatin
   19. Isoniazid (INH)
   20. Macrolides
       1. Erythromycin
       2. Clarithromycin
   21. Metronidazole (Flagyl)
       1. High risk Drug Interaction (can significantly increase INR with bleeding risk 2-4 fold over baseline)
       2. Avoid if possible and if not, consider decreasing Warfarin dose by 25-40%
   22. Nalidixic Acid
   23. NSAIDs
       1. Increased risk of gastric erosions and irritation with secondary Gastrointestinal Bleeding risk
       2. Avoid NSAIDs in those on Warfarin (use other Analgesics)
   24. Omeprazole (Prilosec)
   25. Paroxetine (Paxil)
   26. Penicillin
   27. Propafenone (Rythmol)
   28. Quinidine
   29. Quinolones
   30. Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
       1. Fluvoxamine (Luvox)
       2. Fluoxetine (Prozac)
       3. One additional patient on Warfarin for Atrial Fibrillation with SNRI or SSRI will have have a major bleeding event
          1. (2014) Presc Lett 21(11): 65
          2. Sansone (2009) Psychiatry 6(7): 24–29 [PubMed]
   31. Sulfinpyrazone (Anturane)
   32. Tamoxifen
   33. Tetracycline
   34. Thyroid Hormone (Thyroxine or Synthroid)
   35. Ticlopidine (Ticlid)
   36. Trimethoprim-Sulfamethoxazole (Bactrim, Septra)
       1. High risk Drug Interaction (can significantly increase INR with bleeding risk 2-4 fold over baseline)
       2. Avoid if possible and if not, consider decreasing Warfarin dose by 25-40%
   37. Vitamin E
       1. Theoretical bleeding risk, but appears to be safe in clinical trials
       2. Dereska (2006) J Surg Res 132:121-9 [PubMed]
5. Drug Interactions: Drugs that decrease INR or increase clotting risk
   1. American Ginseng (no effect on Warfarin with Asian Ginseng)
   2. Barbiturates
   3. Binding Resins
   4. Carbamazepine (Tegretol)
   5. Oral Contraceptives
   6. Penicillin
   7. Rifampin
      1. Avoid if possible and if not, consider increasing Warfarin dose by 25-50%
   8. St. John's Wort
   9. Vitamin K
6. Drug Interactions: Drugs that have a variable effect on INR or bleeding risk
   1. Allopurinol
   2. Corticosteroids
   3. Phenytoin (Dilantin)
7. Drug Interactions: Lowest risk antibiotics for interaction
   1. Amoxicillin
   2. Azithromycin
   3. Cepahlosporins
8. References
   1. Carpenter (2019) Am Fam Physician 99(9): 558-64 [PubMed]
   2. Horton (1999) Am Fam Physician [PubMed]
   3. Gage (2000) Am J Med 109:484 [PubMed]