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KMID : 0869620130300010052
Journal of Korean Society of Hospital Pharmacists
2013 Volume.30 No. 1 p.52 ~ p.63
Proposal for Warfarin Dosage Guideline during Warfarin-Propafenone Combination Therapy
Park Seon-Mi

Min Kyoung-A
In Yong-Won
Lee Young-Mee
Abstract
Oral anticoagulation therapy with warfarin is effective in the prevention of stroke during atrial fibrillation, but it needs careful monitoring because of its narrow therapeutic range and complexity of interaction with other medications. Propafenone is an antiarrhythmic agent
classified in the class I c category. A previous study provided clinical evidence for a possible interaction between warfarin and propafenone. The addition of propafenone can potentiate the anticoagulant effect of warfarin so the previous study recommended a close monitoring and reduction of warfarin dosage when co-administered with propafenone. However, no reports have established an appropriate warfarin dosage guideline. Therefore, this study was conducted to determine the appropriate dosage of warfarin when co-administered with propafenone in regards to developing a practical guideline.
A retrospective analysis was done for all patients who received propafenone, seen by the anticoagulation service (ACS) at Samsung Medical Center from January 1, 2008 to January 31, 2011.
Patients who had consistent therapeutic INR values (1.8-3.2) with the same dose of warfarin for at least 1 month and who had not received any drugs known to alter INR values or interact with warfarin were included in the study.
A total of twenty four patients met the inclusion criteria. The 1st ACS follow-ups were performed on day 7.63¡¾3.85 and increases in INR were observed. The reduction rate in the warfarin dose for maintaining therapeutic INR was 10.08¡¾6.79%. There was a significant difference in the reduction of the warfarin dose between the baseline and the 1st ACS follow-up. No significant differences were observed in the reduction of warfarin dose between the 1st ACS follow-up and 2nd ACS follow-up. Although no major bleeding was observed in the study group, 2 cases of minor bleeding (bruise and gingival bleeding) occurred during the study period. Based on these findings, we recommend a 10-15% reduction in the dose of warfarin at the time propafenone treatment is started and INR values should be determined on day 7-10 to ensure that therapeutic INR levels are maintained.
This study provides a clinically available warfarin dosage guideline in the concomitant use of propafenone and warfarin. In addition, based on the results of this study, additional prospective study should be needed.
KEYWORD
Warfarin, Propafenone, Drug interaction, INR (International Normalized Ratio)
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