Abstract
Objective:
To determine whether acetaminophen, opiates, or acetaminophen–opiate combinations potentiate the effect of warfarin.
Data Sources:
Previous studies or reports of interactions between warfarin and acetaminophen, opiates, or acetaminophen–opiate combinations (MEDLINE search, January 1976 to January 1996).
Study Selection:
All articles were included in the review. Pertinent information was selected for discussion.
Data Synthesis:
Studies of the effects of acetaminophen on anticoagulation with warfarin and other oral anticoagulants have yielded conflicting results. In three placebo-controlled studies of patients or healthy men, acetaminophen 2–4 g/d for 2–3 weeks potentiated the anticoagulant effect of warfarin and other related drugs compared with placebo. Similar findings were seen in one uncontrolled study of patients taking acetaminophen 2.6 g/d for 4 weeks, but not in another in which patients took acetaminophen 3.25 g/d for 14 days. Other studies showed that two doses of acetaminophen 650 mg for 1 day did not influence the prothrombin time. There were six reports of adverse interactions between warfarin and acetaminophen–opiate combinations. Of five patients who were given an acetaminophen–propoxyphene combination, the equivalent daily doses of acetaminophen and propoxyphene were specified for four and ranged from 1.95 to 6.5 g and from 195 to 1,000 mg, respectively. The duration of therapy in the five patients ranged from less than 1 day to 10 days. One of these patients also received ibuprofen. Another patient took an unspecified acetaminophen–codeine product equivalent to acetaminophen 1.56 g/d. The exact mechanism underlying such interactions is not clear.
Conclusions:
During the combined use of warfarin and acetaminophen (in high daily doses for 2–3 wk) or acetaminophen–propoxyphene combinations, patients should be closely monitored for anticoagulant control and bleeding complications.
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