Division of Internal Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Ann Pharmacother. 2010 May;44(5):926-8. doi: 10.1345/aph.1M715. Epub 2010 Mar 23.
To report a case of imatinib-induced hepatotoxicity after concurrent ginseng ingestion in a patient with chronic myelogenous leukemia (CML).
A 26-year-old man with CML who had taken imatinib 400 mg daily for 7 years with no complications presented with right upper quadrant pain. Laboratory test results included alanine aminotransferase 1069 U/L, aspartate aminotransferase 481 U/L, alkaline phosphatase 124 IU/L, total bilirubin 1.4 mg/dL, albumin 4.0 g/dL, and international normalized ratio 1.08. Liver biopsy showed acute lobular hepatitis favoring a drug-induced etiology, and a diagnosis of imatinib-induced hepatotoxicity was made. The patient's only lifestyle modification prior to the diagnosis of hepatotoxicity was daily ingestion of Panax ginseng via energy drinks for the past 3 months. Both imatinib and ginseng were discontinued, and the patient was treated with a short course of corticosteroids. Imatinib was later restarted at the same dose with no recurrent elevations in his liver enzyme levels.
Imatinib-associated hepatotoxicity usually presents within 1-2 years of therapy initiation, with the median time to hepatotoxicity being 100 days. Ginseng is an herb that is not known to be hepatotoxic. In vivo, ginseng is known to inhibit CYP3A4, the primary enzyme involved in the metabolism of imatinib. We propose that our patient's late-onset imatinib-associated hepatotoxicity was due to an interaction between ginseng and imatinib through CYP3A4. Based on the Naranjo probability scale, it is probable that imatinib caused this patient's hepatotoxicity, and the Horn drug interaction probability scale also indicates a probable interaction between imatinib and ginseng.
This case emphasizes the importance of continuous monitoring of liver function tests even after several years of imatinib therapy and the importance of advising patients to avoid ginseng and any other over-the-counter herbal supplements that may interact with imatinib.
报告 1 例慢性髓性白血病（CML）患者同时服用人参后伊马替尼诱导的肝毒性。
1 例 26 岁男性，CML 患者，每日服用伊马替尼 400mg 已 7 年，无并发症，出现右上腹疼痛。实验室检查结果包括丙氨酸氨基转移酶 1069U/L、天冬氨酸氨基转移酶 481U/L、碱性磷酸酶 124IU/L、总胆红素 1.4mg/dL、白蛋白 4.0g/dL、国际标准化比值 1.08。肝活检显示急性肝小叶肝炎，支持药物引起的病因，诊断为伊马替尼诱导的肝毒性。在诊断肝毒性之前，患者唯一的生活方式改变是过去 3 个月每天通过能量饮料摄入人参。伊马替尼和人参均已停用，患者接受了短期皮质类固醇治疗。随后以相同剂量重新开始使用伊马替尼，其肝酶水平未再次升高。
伊马替尼相关肝毒性通常在治疗开始后 1-2 年内出现，肝毒性的中位时间为 100 天。人参是一种已知无肝毒性的草药。在体内，人参已知可抑制 CYP3A4，这是参与伊马替尼代谢的主要酶。我们提出，我们患者的迟发性伊马替尼相关肝毒性是由于人参和伊马替尼通过 CYP3A4 相互作用引起的。根据 Naranjo 概率量表，伊马替尼极有可能导致该患者的肝毒性，Horn 药物相互作用概率量表也表明伊马替尼和人参之间可能存在相互作用。
该病例强调了即使在伊马替尼治疗数年后也需要持续监测肝功能检查，并告知患者避免人参和任何其他可能与伊马替尼相互作用的非处方药草药补充剂的重要性。
