Dosage Adjustment before and after Warfarin - Rifampin Combination Therapy

Kim, Dong Hyun; Kim, Kyung Hwan; Choi, Kyung Hee; Lee, Kwang Ja; Lee, Hye Suk; Son, In Ja; Kim, Ki Bong; Lee, Jae Woong; Ahn, Hyuk

Abstract

BACKGROUND: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin - rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. MATERIAL AND METHOD: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan 1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). RESULT: The average INR of all the patient before rifampin administration was 2.25+/-0.52 (mean+/-SD), and that value for the first 100 days after rifampin administration was 1.98+/-0.28. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was 2.19+/-0.34, and the value after rifampin cessation was 2.49+/-0.43. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range.
CONCLUSION
The warfarin dose adjustment equation of before and after warfarin - rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.