OBJECT DRUGS

Anticoagulants, Oral:

• Acenocoumarol
• Phenprocoumon
• Warfarin (Coumadin, etc.)

PRECIPITANT DRUGS

Analgesics:

• Acetaminophen (Tylenol, etc.)
• Aspirin

Comment:

Aspirin increases the risk of bleeding in anticoagulated patients due to inhibition of platelet function and gastric erosions. Large doses of aspirin (e.g. 3g/day or more) can increase the hypoprothrombinemic response. However, low (antiplatelet) doses of aspirin appear to increase primarily minor bleeding and the combination is used intentionally in many patients. In some patients, acetaminophen can increase the hypoprothrombinemic response to warfarin and probably other oral anticoagulants. In most cases the interaction is small, but in predisposed patients marked hypoprothrombinemia has been reported. It would be prudent to limit acetaminophen dosage to 2 g/day or less for no more than a few days, and to monitor the INR.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative: As an analgesic, acetaminophen appears safer than aspirin for patients on warfarin (but avoid large or prolonged doses of acetaminophen). If a NSAID is required, see Anticoagulants, Oral+NSAIDs. Most opiates appear to have little effect on the anticoagulant response to warfarin, but there are case reports of increased warfarin effect due to tramadol (Ultram).
• Circumvent/Minimize: Advise patients on oral anticoagulants to avoid taking acetaminophen, aspirin or other salicylates unless instructed to do so by the prescriber of the oral anticoagulant.
• Monitor: Monitor the INR if acetaminophen or large doses of salicylates are given for more than a few days. Note that the increased bleeding risk from small doses of aspirin (e.g., less than 2 to 3 g/day) is usually not reflected in an increased INR or prothrombin time. Monitor carefully for clinical evidence of bleeding, especially from the gastrointestinal tract.