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Eur J Clin Pharmacol ; 67(3): 309-14, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21191575

ABSTRACT

PURPOSE: We investigated whether acetaminophen, given at 2 g/day and 3 g/day might potentiate the anticoagulant effect of warfarin. METHODS: Forty-five patients on stable warfarin therapy, enrolled in this prospective, randomized, parallel (three arms), placebo-controlled study, received a 10-day regimen of acetaminophen (2 g/day or 3 g/day) or placebo. RESULTS: The mean maximal INR increase was 0.70 ± 0.49 and 0.67 ± 0.62 in patients receiving acetaminophen at 2 g/day and 3 g/day, respectively (P=0.01 for the respective comparisons versus placebo). The INR increase became significant on day 3 and was independently and significantly predicted by a maximal decrease in factor II (R(2)=0.36, P<0.0001), factor VII (R (2)=0.46, P<0.0001) and a maximal increase in acetaminophen plasma concentrations (R(2)=0.563, P<0.0001). CONCLUSION: Acetaminophen, at 2 g/day or 3 g/day, enhanced the anticoagulant effect of warfarin in stable patients, thus requiring close INR monitoring in the clinical setting.


Subject(s)
Acetaminophen/pharmacology , Analgesics, Non-Narcotic/pharmacology , Anticoagulants/pharmacology , Warfarin/pharmacology , Acetaminophen/administration & dosage , Acetaminophen/pharmacokinetics , Administration, Oral , Adult , Aged , Aged, 80 and over , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/pharmacokinetics , Dose-Response Relationship, Drug , Double-Blind Method , Drug Interactions , Drug Monitoring/methods , Female , Humans , International Normalized Ratio , Male , Middle Aged , Prospective Studies , Young Adult
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