II. Risk Factors: Drug Interaction with Warfarin

  1. Older age
  2. Acutely ill
  3. Dietary change
  4. Concurrent infection

III. 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 5 days after starting medication
    2. Check INR after stopping the medication

IV. Drug Interactions: Agents that increase INR or bleeding risk

  1. Acetaminophen (Tylenol)
  2. Alcohol
  3. Amiodarone (Cordarone)
    1. 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%
    2. Reference
      1. Sanoski (2002) Chest 121:19-23
  4. Anabolic Steroids
  5. Antifungal Medications
    1. Fluconazole (Diflucan)
    2. Ketoconazole (Nizoral)
    3. Itraconazole (Sporanox)
    4. Miconazole (Monistat)
  6. Aspirin and Salicylates
  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
  12. Danazol (Danocrine)
  13. Diflunisal (Dolobid)
  14. Disulfiram (Antabuse)
  15. Fluvoxamine (Luvox)
  16. Ginkgo Biloba (independent effect due to antiplatelet activity)
  17. Heparin
  18. HMG CoA Reductase inhibitors
  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 Septra dose by 25-40%
  22. Nalidixic Acid
  23. NSAIDs
  24. Omeprazole (Prilosec)
  25. Paroxetine (Paxil)
  26. Penicillin
  27. Propafenone (Rythmol)
  28. Quinidine
  29. Quinolones
  30. Sulfinpyrazone (Anturane)
  31. Tamoxifen
  32. Tetracycline
  33. Thyroid Hormone (Thyroxine or Synthroid)
  34. Ticlopidine (Ticlid)
  35. 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 Septra dose by 25-40%
  36. Vitamin E
    1. Theoretical bleeding risk, but appears to be safe in clinical trials
    2. Dereska (2006) J Surg Res 132:121-9

V. 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 25-40%
  8. St. John's Wort
  9. Vitamin K

VI. Drug Interactions: Drugs that have a variable effect on INR or bleeding risk

VII. Drug Interactions: Lowest risk antibiotics for interaction

  1. Amoxicillin
  2. Azithromycin
  3. Cepahlosporins

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