Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial

Zhang, Qian; Bal-dit-Sollier, Claire; Drouet, Ludovic; Simoneau, Guy G.; Alvarez, Jean‐Claude; Pruvot, S.; Aubourg, R.; Berge, Natacha; Bergmann, Jean‐François; Mouly, Stéphane; Mahé, Isabelle

doi:10.1007/s00228-010-0975-2

Cited by 36 publications

(24 citation statements)

References 16 publications

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“…In addition, statins have been shown to exhibit anticoagulant properties [40]. Paracetamol, when used at daily doses exceeding 2000 mg, is suspected to potentiate warfarin response [41][42][43] A Incident users without previous use of NSAIDs, paracetamol or tramadol B Incident users with previous use of NSAIDs C Incident users with previous use of paracetamol D Incident users with previous use of tramadol NSAIDs = Non-steroidal anti-inflammatory drugs Fig. 1.…”

Section: Discussionmentioning

confidence: 99%

Co‐Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population‐Based Register Study

Rikala

Hauta-Aho

Helin‐Salmivaara

et al. 2015

Basic Clin Pharma Tox

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Abstract:We analysed the occurrence of co-prescribing of potentially interacting drugs during warfarin therapy in the community-dwelling population of Finland. We identified drugs having interaction potential with warfarin using the Swedish Finnish INteraction X-referencing drug-drug interaction database (SFINX) and obtained data on drug purchases from the nationwide Prescription Register. We defined warfarin users as persons purchasing warfarin in 2010 (n = 148,536) and followed them from their first prescription in 2010 until the end of the calendar year. Co-prescribing was defined as at least 1-day overlap between warfarin and interacting drug episodes. In addition, we identified persons who initiated warfarin therapy between 1 January 2007 and 30 September 2010 (n = 110,299) and followed these incident users for a 3-month period since warfarin initiation. Overall, 74.4% of warfarin users were co-prescribed interacting drugs. Co-prescribing covered 46.4% of the total person-years of warfarin exposure. Interacting drugs that should be avoided with warfarin were co-prescribed for 13.4% of warfarin users. The majority of the co-prescriptions were for drugs that are not contraindicated during warfarin therapy but require special consideration. Among incident users, 57.1% purchased potentially interacting drugs during the 3-month period after initiation, while 9.0% purchased interacting drugs that should be avoided with warfarin. To conclude, the occurrence of co-prescribing of potentially interacting drugs was high during warfarin therapy. Our findings highlight the importance of close monitoring of warfarin therapy and the need for further studies on the clinical consequences of co-prescribing of interacting drugs with warfarin.

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Section: Discussionmentioning

confidence: 99%

Co‐Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population‐Based Register Study

Rikala

Hauta-Aho

Helin‐Salmivaara

et al. 2015

Basic Clin Pharma Tox

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“…McNemar test was used for comparing the differences in the use of individual drugs between time points, and Fisher's exact test was for comparing the differences between frailty groups No statistically significant differences were observed in the proportions of users between frailty categories at discharge a NSAIDs include indomethacin, meloxicam and ibuprofen (combination products) Tramadol impairs platelet function by inhibiting serotonin reuptake to platelets [30] and its concomitant use with warfarin is also associated with excess anticoagulation [31][32][33][34]. A metabolite of acetaminophen, N-acetyl-p-benzoquinone, interferes with vitamin K metabolism and the synthesis of coagulation factors [35] thereby potentiating the warfarin response [36][37][38]. Moreover, acetaminophen may also have antiaggregatory effects [39].…”

Section: Discussionmentioning

confidence: 99%

Frailty and Co-Prescribing of Potentially Interacting Drugs in New Users of Warfarin

et al. 2020

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Background Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known. Objective The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients. Methods We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation. Results In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively. Conclusions The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

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“…The assertion that APAP affects vitamin K-dependent factor activation is further supported by several other studies that found that APAP increased the INR in patients previously on stable warfarin therapy. This typically occurred when daily doses of APAP exceed 2-4 g/day for several days [14][15][16][17]. There was significant debate in the literature regarding these findings as there did not appear to be a plausible explanation based on pharmacokinetic and cytochrome P450 mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Prothrombin Time and Aspartate Aminotransferase in Predicting Hepatotoxicity After Acetaminophen Overdose

et al. 2015

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Despite decades of experience with acetaminophen (APAP) overdoses, it remains unclear whether elevated hepatic transaminases or coagulopathy develop first. Furthermore, comparison of the predictive value of these two variables in determining hepatic toxicity following APAP overdoses has been poorly elucidated. The primary objective of this study is to determine the test characteristics of the aspartate aminotransferase (AST) and the prothrombin time (PT) in patients with APAP toxicity. A retrospective chart review of APAP overdoses treated with IV N-acetylcysteine at a tertiary care referral center was performed. Of the 304 subjects included in the study, 246 with an initial AST less than 1000 were analyzed to determine predictors of hepatic injury, defined as an AST exceeding 1000 IU/L. The initial AST >50 was 79.5 % sensitive and 82.6 % specific for predicting hepatic injury. The corresponding negative and positive predictive values were 95.5 and 46.3 %, respectively. In contrast, an initial abnormal PT had a sensitivity of 82.1 % and a specificity of 63.6 %. The negative and positive predictive values for initial PT were 94.9 and 30.2 %, respectively. Although the two tests performed similarly for predicting a composite endpoint of death or liver transplant, neither was a useful predictor. Initial AST performed better than the initial PT for predicting hepatic injury in this series of patients with APAP overdose.

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Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial

Abstract: 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.

Cited by 36 publications

References 16 publications

Co‐Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population‐Based Register Study

Co‐Prescribing of Potentially Interacting Drugs during Warfarin Therapy – A Population‐Based Register Study

Frailty and Co-Prescribing of Potentially Interacting Drugs in New Users of Warfarin

Comparison of Prothrombin Time and Aspartate Aminotransferase in Predicting Hepatotoxicity After Acetaminophen Overdose

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