Abstract: Objective To investigate the influencing frequency and degree of azole antifungal agents on anticoagulation activity of warfarin in order to reduce potential bleeding risk and provide reference for safe drug use. Methods Inpatient cases from January 1st 2010 to November 1st 2015 were screened to identify those who used warfarin in combination with azole antifungal agents, and relevant clinical data was extracted for analysis. Results Totaled 27 cases were included among which 21 cases received fluconazole and 6 cases received voriconazole in combination with warfarin therapy. 22 cases (81.48%) had INR values higher by 20% after co-administration than baseline levels with warfarin alone. Compared with the INR values with warfarin alone, INR values increased by 2.18 folds (P<0.000 1) and 2.59 folds (P=0.006 9) respectively after co-administration with fluconazole and voriconazole. Warfarin sensitivity index (WSI) was also calculated in order to diminish the influence of warfarin dosage adjustment on INR values. Compared with the WSI values with warfarin alone, INR values increased by 2.07 folds (P<0.000 1) and 3.28 folds (P=0.009 6) respectively after co-administration with fluconazole and voriconazole. INR values in some cases rose significantly as early as 2 days after co-administration and reached peak values on the 7th day. Conclusion Co-administration of warfarin and azole antifungal agents can significantly enhance anticoagulation activity of warfarin by 2 folds and INR values should be closely monitored within 1 week after co-administration in order to prevent bleeding events.

Key words: warfarin, azole antifungal agents, drug interaction