Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a...
Transcript of Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a...
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Interaction between acetaminophen and warfarin in adults
receiving long-term oral anticoagulants: a
randomized controlled trial
นศภ.ณั�ฐวุ�ฒิ ดวุงแดง มหาวุทยาลั�ยเชี�ยงใหม�นสภ.จตุ�พร ใจเคลั !อน มหาวุทยาลั�ยพะเยานสภ.อ�งสนา เพ$ญสมบู'รณั(มหาวุทยาลั�ยพะเยา
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Title
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impact factor = 2.743
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Abstract
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IntroductionThe mean INR increase in
patients receiving acetaminophen at the highest recommended dosage (4 g/day)
No prospective study has yet evaluated the effect of acetaminophen at 3 g/day
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Acetaminophen given at 2 g/day and
3 g/day might potentiate the anticoagulant
effect of warfarin
Research questions
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Objective
To evaluate the effect of acetaminophen, given at 2 g/day and 3 g/day, on INR in stable patients treated with warfarin
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Study Designrandomized, parallel (three arms), double-blind, placebo-controlled study
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Inclusion criteria
Patients treated with warfarin (target INR 2 to 3) stable anticoagulation at 2 to 9 mg for more than 30 days
Aged 18 years or olderLaboratory values remained within normal limits
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Exclusion criteriaAny treatment change
within 7 days before enrollment
Any paracetamol intake within the last 14 days
St John's wort treatment
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Exclusion criteriaDrug allergy Concomitant
drug ( 5-fluorouracile, acetylsalicylic acid, non steroidal anti-inflammatory drugs, chloramphenicol, diflunisal, miconazole)
Pregnancy
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Drop outINR value were higher than 3.5
Drug known to interact with warfarin or acetaminophen
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Method45 Patients
Control group (9)Experimental group (36)
2 g/day (18) 3 g/day (18)
Placebo (9) Acetaminophen
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Method
Placebo two placebo tablets three times a day
two placebo tablets three times a day
2 g/daytwo 500 mg tablets twice a day+ two placebo tablets once dailytwo 500 mg tablets twice a day
+ two placebo tablets once daily
3 g/daytwo 500 mg tablets three times a day
two 500 mg tablets three times a day
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Outcome Primary outcome - The mean maximum increase in INR from
baseline to Day 10 secondary outcome - The mean maximum INR - Day 10 - Day 1 differences in factors II, V, VII, AT-III plasma concentrations between groups
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Outcome secondary outcome - Day 10 - Day 1 differences in acetaminophen plasma concentration between groups- Day 10 - Day 1 differences in R(-), S(-)warfarin plasma concentrations between groups- Day 10 - Day 1 differences in Gla-type Osteocalcin and undercarboxylated Osteocalcin plasma concentrations between groups
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StatisticsSample size and percent drop out
There are 45 pt. in these study.- intra-individual INR variability is 0.3
- expected INR increase of at least 0.5- bilateral α level of 5% แลัะ β level of 10%-No drop out
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Statisticsควุามเหมาะสมของสถิตุท�!ใชี+กั�บูชีนดของตุ�วุแปร
- ANOVA-post-hoc test-All statistical analyses were implemented by using Statview v8.0 (SAS Institute, Cary, NC, USA)- Results were expressed as mean and 95% confidence interval (CI), or as a percentage, as appropriate. A P value of 0.05 or less indicated statistical significance
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Result
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Result
Fig. 1 Correlation between INR changes and
acetaminophen plasma concentrations
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Result
Fig. 2 Correlation between INR changes and factors II
plasma concentrations
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Result
Fig. 3 Correlation between INR changes and factors VII
plasma concentrations
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The lack of variables follow up after withdrawal of acetaminophen
The unexpected imbalance observed in the randomization of the population regarding age, gender and basal warfarin dose
Limitation of Research
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Conclusion
- Acetaminophen, 2 g/day and 3 g/day significantly increased the INR in patients treated with warfarin - Recommend close INR monitoring in patients taking acetaminophen during warfarin therapy
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Generalizability
- European pt. -> Genetics variation- Life style and environment- Other drugs and agents- Disease
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Thank you