唑类抗真菌药物对华法林抗凝活性影响的临床分析和比较

摘要

Objective To investigate the inlfuencing 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 lfuconazole 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 lfuconazole and voriconazole. Warfarin sensitivity index (WSI) was also calculated in order to diminish the inlfuence 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 lfuconazole and voriconazole. INR values in some cases rose signiifcantly 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 signiifcantly 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.%目的：研究临床联用唑类抗真菌药对华法林抗凝活性影响的频率和程度,以降低潜在的出血风险,为临床安全用药提供指导。方法通过电子病历系统筛选并纳入自2010年1月1日~2015年11月1日期间联用华法林和唑类抗真菌药的住院患者,提取患者临床资料。结果共纳入27例患者,其中21例联用氟康唑,6例联用伏立康唑,22例（81.48%）患者INR值升高超过20%。与单用华法林相比,联用氟康唑和伏立康唑后INR值分别平均升高2.18倍（P<0.0001）和2.59倍（P=0.0069）。计算华法林敏感指数（INR/华法林日剂量, WSI）以减少华法林剂量调整对INR值的影响。与单用华法林的WSI值相比,联用氟康唑和伏立康唑后INR值分别升高2.07倍（P<0.0001）和3.28倍（P=0.0096）。联用2天即可出现INR值明显升高,联用1周时相互作用达到峰值。结论联用唑类抗真菌药可显著增强华法林抗凝作用2倍左右,联用1周内应密切监测患者的INR值,以避免出血事件发生。