Ciorciaro C, Hartmann K, Stoller R, Kuhn M
Schweizerische Arzneimittel-Nebenwirkungszentrale (SANZ), Chur.
Schweiz Med Wochenschr. 1996 Dec 7;126(49):2109-13.
Drug-induced liver diseases are potentially avoidable. Hepatotoxic drugs can mimic virtually any form of liver disease. Among all voluntary adverse drug reaction reports to central registries, 4-7% refer to drug-induced liver diseases. We analyze all cases of coumarin-induced hepatic injuries reported on a voluntary basis to the Swiss Drug Monitoring Centre (SANZ) and the Pharmacovigilance Centre (IKS) from 1981 to 1995. During this period the SANZ collected 9720 reports, 674 of which (6.9%) referred to the liver and the biliary tract. In only 11 reports an oral anticoagulant was involved. In 8 cases we assumed at least a possible causal relationship. 2 more cases were reported directly to the IKS. Among these 10 cases 7 were related to phenprocoumon and 3 to acenocoumarol. In 4 cases elevated concentrations of liver enzymes were measured 2-7 days after the beginning of therapy. In the remaining 6 cases the clinical picture was so severe that the patients had to be hospitalized. These 10 cases are discussed and compared with the cases published in the literature. According to our data, hepatic disorders induced by coumarin-anti-coagulants are rare. If hepatitis is diagnosed in a patient treated with oral anticoagulants, the differential diagnosis of a coumarin-induced hepatic injury has to be considered. Crossreactions between the coumarin derivatives phenprocoumon and acenocoumarol are possible.
药物性肝病是有可能避免的。肝毒性药物几乎可以模拟任何形式的肝病。在所有向中央登记处自愿报告的药物不良反应中,4%至7%涉及药物性肝病。我们分析了1981年至1995年期间自愿向瑞士药物监测中心(SANZ)和药物警戒中心(IKS)报告的所有香豆素引起的肝损伤病例。在此期间,SANZ收集了9720份报告,其中674份(6.9%)涉及肝脏和胆道。只有11份报告涉及口服抗凝剂。在8例中,我们认为至少存在可能的因果关系。另外2例直接报告给了IKS。在这10例中,7例与苯丙香豆素有关,3例与醋硝香豆素有关。4例在治疗开始后2至7天测量到肝酶浓度升高。其余6例临床表现严重,患者不得不住院治疗。对这10例病例进行了讨论,并与文献中发表的病例进行了比较。根据我们的数据,香豆素类抗凝剂引起的肝脏疾病很少见。如果在接受口服抗凝剂治疗的患者中诊断出肝炎,必须考虑香豆素引起的肝损伤的鉴别诊断。香豆素衍生物苯丙香豆素和醋硝香豆素之间可能存在交叉反应。