非诺贝特与华法林相互作用致血尿1例及文献复习

Interaction Between Fenofibrate and Warfarin Experienced Hematuria: Case Report and Review of the Literature

关键词:  华法林  非诺贝特  相互作用

Key words:  warfarin  fenofibrate  interaction

摘要:

目的 探讨非诺贝特对华法林抗凝作用的影响、作用机制和处理方法。方法 1位78岁老年男性患者长期稳定服用华法林抗凝治疗，在服用非诺贝特2周后出现咳血、血尿和左下肢疼痛，急诊查INR值为5.9，予停用华法林、肌注维生素K1 10 mg处理后出院，随后根据INR值调整华法林周剂量下降40%后INR值达到稳定，半个月后患者因肌痛停用非诺贝特，INR值连续2周持续下降，调整华法林剂量至接近服用非诺贝特前。结果 患者在稳定的华法林治疗剂量基础上加用非诺贝特后，增加了华法林的抗凝效果。非诺贝特蛋白结合率高，可能把与白蛋白结合的华法林置换下来，导致抗凝效果增强；非诺贝特也是轻到中度的CYP2C9抑制剂，CYP2C9为S型华法林的代谢酶。这2种作用合起来可增强华法林的药效。结论 在长期华法林稳定抗凝治疗的情况下加用非诺贝特后，建议连续监测INR值并考虑经验性降低华法林剂量20%，之后根据INR值继续调整剂量至稳定。

Abstract:

OBJECTIVE To explore the interaction between fenofibrate and warfarin as well as the mechanism of action. METHODS The case of 78-year-old man received stable warfarin therapy before initiation of fenofibrate. After 1 week, the patient experienced hemoptysis and hematuria. On admission to the emergency department, the INR was 5.9, so warfarin was discontinued and using vitamin K1 administered intramuscularly. Adjusted the dosage of warfarin based on the INR after discharge and warfarin dose was reduced by 40%. Half month later he discontinued fenofibrate because of myalgia and INR declined for two consecutive weeks. The dosage of warfarin was adjusted and the patient’s INR remained stable. RESULTS The addition of fenofibrate on stable and therapeutic doses of warfarin increased the anticoagulant response to warfarin. Fenofibrate was highly protein bound, with the potential to displace warfarin from its binding protein, leading to an enhanced anticoagulant effect. Fenofibrate was also a mild to moderate inhibitor of CYP2C9, the enzyme was responsible for S-warfarin metabolism. The combination of the two effects may increase the anticoagulant response to warfarin. CONCLUSION It is suggested that serial monitoring of INR and consider an empiric 20% reduction in warfarin dosage when fenofibrate is initiated when patient on stable and therapeutic dose of warfarin.