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Warfarin Drug Interactions
Aka: Warfarin Drug Interactions, Drug Interactions with Coumadin, Coumadin Drug Interactions
- See Also
- Coumadin (Warfarin)
- Coumadin Protocol
- Coumadin Protocol for the Perioperative Period
- Risk Factors: Drug Interaction with Warfarin
- Older age
- Acutely ill
- Dietary change
- Concurrent infection
- Precautions
- Avoid using agents with major Drug Interactions with Warfarin
- When using medications known to affect INR, monitor INR closely
- Check INR 3-5 days after starting medication
- Check INR 3-5 days after stopping the medication
- Other non-medication factors potentiate Anticoagulation effect
- Diarrhea
- Fever
- Hyperthyroidism
- Congestive Heart Failure
- Liver Disease
-
Drug Interactions: Agents that increase INR or bleeding risk
- Acetaminophen (Tylenol)
- Limit Acetaminophen dose to 2 grams per day for 7 days
- Consistent use of Acetaminophen may require more frequent monitoring of INR
- Alcohol (acute intake)
- Amiodarone (Cordarone)
- Precaution
- Amiodarone has a very long half-life and interaction persist for weeks after discontinuation
- Adjustment per Amiodarone maintenance dose
- Amiodarone 400 mg/day: Reduce Warfarin dose 40%
- Amiodarone 300 mg/day: Reduce Warfarin dose 35%
- Amiodarone 200 mg/day: Reduce Warfarin dose 30%
- Amiodarone 100 mg/day: Reduce Warfarin dose 25%
- Reference
- Sanoski (2002) Chest 121:19-23 [PubMed]
- Anabolic Steroids
- Antifungal Medications (Azoles)
- High risk Drug Interaction
- May significantly increase INR and bleeding risk
- Avoid if possible and if not, consider decreasing Warfarin dose by 25-30%
- Fluconazole (Diflucan)
- Ketoconazole (Nizoral)
- Itraconazole (Sporanox)
- Miconazole (Monistat)
- Voriconazole (Vfend)
- Aspirin and Salicylates
- Increased risk of gastric erosions and irritation with secondary Gastrointestinal Bleeding risk (as with NSAIDs)
- Platelet inhibition increases overall bleeding risk
- When required (e.g. Coronary Artery Disease, prior CVA), limit Aspirin dose to 81 mg orally daily
- Cephalosporins
- Cefoperazone (Cefobid)
- Cefamandole (Mandol)
- Cefotetan (Cefotan)
- Cefmetazole (Zefazone)
- Chloral Hydrate
- Cimetidine (Tagamet)
- Clofibrate
- Cranberry Juice (CYP2C9 inhibitor)
- Appears safe in at least one clinical trial
- Greenblatt (2006) Clin Pharmacol Ther 79:125-33 [PubMed]
- Danazol (Danocrine)
- Devil's Claw
- Diflunisal (Dolobid)
- Diltiazem
- Disulfiram (Antabuse)
- Garlic
- Gemfibrozil (Lopid)
- Ginkgo Biloba (independent effect due to antiplatelet activity)
- Heparin
- HMG CoA Reductase inhibitors or Statins (via CYP2C9 inhibition)
- Highest risk: Fluvastatin, Lovastatin, Rosuvastatin, Simvastatin
- Lowest risk: Atorvastatin, Pravastatin
- Isoniazid (INH)
- Macrolides
- Erythromycin
- Clarithromycin
- Metronidazole (Flagyl)
- High risk Drug Interaction (can significantly increase INR with bleeding risk 2-4 fold over baseline)
- Avoid if possible and if not, consider decreasing Warfarin dose by 25-40%
- Nalidixic Acid
- NSAIDs
- Increased risk of gastric erosions and irritation with secondary Gastrointestinal Bleeding risk
- Avoid NSAIDs in those on Warfarin (use other Analgesics)
- Omeprazole (Prilosec)
- Penicillin
- Propafenone (Rythmol)
- Quinidine
- Quinolones (e.g. Ciprofloxacin)
- Selective Serotonin Reuptake Inhibitors (SSRI) and Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
- Fluvoxamine (Luvox)
- Fluoxetine (Prozac)
- Paroxetine (Paxil)
- Sertraline (Zoloft)
- One additional patient on Warfarin for Atrial Fibrillation with SNRI or SSRI will have have a major bleeding event
- (2014) Presc Lett 21(11): 65
- Sansone (2009) Psychiatry 6(7): 24–29 [PubMed]
- Sulfinpyrazone (Anturane)
- Tamoxifen
- Tetracycline
- Thyroid Hormone (Thyroxine or Synthroid)
- Ticlopidine (Ticlid)
- Trimethoprim-Sulfamethoxazole (Bactrim, Septra)
- High risk Drug Interaction (can significantly increase INR with bleeding risk 2-4 fold over baseline)
- Avoid if possible and if not, consider decreasing Warfarin dose by 25-40%
- Vitamin E
- Theoretical bleeding risk, but appears to be safe in clinical trials
- Dereska (2006) J Surg Res 132:121-9 [PubMed]
-
Drug Interactions: Drugs that decrease INR or increase clotting risk
- American Ginseng (no effect on Warfarin with Asian Ginseng)
- Barbiturates
- Binding Resins
- Carbamazepine (Tegretol)
- Oral Contraceptives
- Penicillin
- Rifampin
- Avoid if possible and if not, consider increasing Warfarin dose by 25-50%
- St. John's Wort
- Vitamin K
-
Drug Interactions: Drugs that have a variable effect on INR or bleeding risk
- Allopurinol
- Corticosteroids
- Phenytoin (Dilantin)
-
Drug Interactions: Lowest risk antibiotics for interaction
- Amoxicillin
- Azithromycin
- Cepahlosporins
- References
- Carpenter (2019) Am Fam Physician 99(9): 558-64 [PubMed]
- Horton (1999) Am Fam Physician [PubMed]
- Gage (2000) Am J Med 109:484 [PubMed]
- Wigle (2019) Am Fam Physician 100(7): 426-34 [PubMed]