Drug Interactions

Drug/Drug ClassEffect on INRRecommendations/Comments
Acetaminophen/APAP↑ with higher dosesLimit APAP to 2000mg/day
↑ with binging
↓ with chronic use
Limit to 1-2 EtOH drinks/day
Amiodaroneslow ↑ over timeComplex interaction that takes place over 6-8 weeks. Ultimately expect 25-50% warfarin dose reduction. Check INR q1-2 weeks and make serial adjustments per INR.
Bosentan (Tracleer)
Capecitabine (Xeloda)
DicloxacillinMore significant if course >14 days.
DoxycyclineNot always clinically significant if pt not systemically ill.
Flu VaccineVaries from year to year, but may cause transient rise in INR.
FluconazoleHold warfarin x1 for single dose. Expect 25-50% warfarin dose reduction for extended course.
FluoroquinolonesNot always clinically significant if pt not systemically ill.
Metronidazole (Flagyl)Expect 25-50% warfarin dose reduction.
Phenytoin↓ or ↑ Complex interaction: initially ↑ INR, but then ↓ after prolonged administration. Additionally, warfarin may alter serum phenytoin concentrations.
RifampinExpect 2- to 5-fold increase in warfarin dose requirements.
Sulfamethoxazole (Septra/Bactrim)Expect 25-50% warfarin dose reduction
Thyroid replacement


Increased Risk of Bleeding is Possible when Combining Warfarin With:

  • Antiplatelets
  • Fish Oil/Omega 3 Fatty Acids
  • NSAIDs
  • Other Anticoagulants
  • Steroids
  • Vitamin E