Tsiattalos Andrew S, Patel Anita
Clinical Pharmacist, Critical Care, VA New Jersey Healthcare System, East Orange, NJ, USA.
J Med Case Rep. 2014 Dec 17;8:433. doi: 10.1186/1752-1947-8-433.
Chronic hepatitis C is a leading cause of severe liver disease. Protease inhibitors used to treat these patients are known to have many drug interactions, although there is limited data available between boceprevir and warfarin. This case report is the first in vivo drug interaction reported in the literature.
A 73-year-old African American man was diagnosed with hepatitis C in 2004, and had decided to not initiate therapy. In 2006, he was diagnosed with deep vein thrombosis and pulmonary embolism and was started on warfarin. His international normalized ratio had been stable on a dose of 13.75 mg to 20mg/week over a period of 6 years. A liver biopsy in 2012 revealed marked fibrosis, leading the patient to start hepatitis C treatment with peginterferon alfa-2a, ribavirin and boceprevir. Three weeks after starting boceprevir, his international normalized ratio became subtherapeutic at 1.2. Upon increasing the warfarin dose by 16%, his international normalized ratio remained at 1.2 6 days later. Two months after initiating boceprevir, he reached a therapeutic international normalized ratio. His warfarin dose had been increased by 75% from his dose prior to starting boceprevir, from 15 mg/week to 26.25mg/week. His hepatitis C treatment was discontinued at week 39 of the intended 48 weeks of treatment due to severe thrombocytopenia. Upon discontinuation of boceprevir, his warfarin dose was prophylactically decreased by 17%, which resulted in a subtherapeutic international normalized ratio of 1.48 1 week later. The warfarin dose was subsequently increased by 10% which resulted, 2 weeks later, in a therapeutic international normalized ratio of 2.8. Once stabilized, his new warfarin dose was 23.75 mg/week, 37% higher than his original maintenance dose of 15 mg/week prior to starting boceprevir.
The co-administration of boceprevir and warfarin resulted in a subtherapeutic international normalized ratio. Upon starting boceprevir, his warfarin dose was increased by 75% over 2 months to achieve a therapeutic international normalized ratio. After discontinuing boceprevir, his maintenance dose of warfarin was 37% greater than his original dose. This is an original case report which demonstrates the significant effects of this drug interaction and the importance of monitoring international normalized ratio.
慢性丙型肝炎是严重肝脏疾病的主要病因。用于治疗这些患者的蛋白酶抑制剂已知存在许多药物相互作用，尽管博赛匹韦与华法林之间的可用数据有限。本病例报告是文献中首次报道的体内药物相互作用。
一名73岁的非裔美国男性于2004年被诊断为丙型肝炎，当时决定不开始治疗。2006年，他被诊断为深静脉血栓形成和肺栓塞，并开始使用华法林治疗。在6年的时间里，他的国际标准化比值在每周13.75毫克至20毫克的剂量下一直保持稳定。2012年的肝脏活检显示有明显纤维化，促使患者开始使用聚乙二醇化干扰素α-2a、利巴韦林和博赛匹韦进行丙型肝炎治疗。开始使用博赛匹韦三周后，他的国际标准化比值降至治疗水平以下，为1.2。将华法林剂量增加16%后，6天后他的国际标准化比值仍为1.2。开始使用博赛匹韦两个月后，他的国际标准化比值达到治疗水平。他的华法林剂量比开始使用博赛匹韦前的剂量增加了75%，从每周15毫克增至每周26.25毫克。由于严重血小板减少，他在计划的48周治疗中的第39周停止了丙型肝炎治疗。停用博赛匹韦后，他的华法林剂量预防性降低了17%，导致1周后国际标准化比值低于治疗水平，为1.48。随后将华法林剂量增加10%，2周后国际标准化比值达到治疗水平，为2.8。一旦稳定，他的新华法林剂量为每周23.75毫克，比开始使用博赛匹韦前最初的维持剂量每周15毫克高出37%。
博赛匹韦与华法林联合使用导致国际标准化比值低于治疗水平。开始使用博赛匹韦后，他的华法林剂量在2个月内增加了75%以达到治疗性国际标准化比值。停用博赛匹韦后，他的华法林维持剂量比原来的剂量高37%。这是一份原始病例报告，证明了这种药物相互作用的显著影响以及监测国际标准化比值的重要性。
