Wong Siu-Fun, Jakowatz James G, Taheri Reza
Western University College of Pharmacy, Pomona, California 91766-1854, USA.
Clin Ther. 2005 Dec;27(12):1942-8. doi: 10.1016/j.clinthera.2005.12.002.
In the United States, patients with high-risk stage II or III melanoma are often treated with adjuvant interferon (IFN) therapy for 1 year after surgery. Adverse events associated with IFN alfa-2b use are primarily constitutional symptoms. However, hypertriglyceridemia requiring treatment has been reported.
The aim of this report was to describe a potential drug-drug interaction between IFN alfa-2b and gemfibrozil in a patient with malignant melanoma. The possible mechanism of this potential interaction was examined.
This report presents the case of a 43-year-old male patient weighing 101 kg with newly diagnosed stage III melanoma of the left arm, with metastasis to the supraclavicular node. The patient presented to the University of California Irvine Medical Center, Orange, California with severe gastrointestinal (GI) symptoms and elevated hepatic enzyme concentrations at week 48 of 104 of adjuvant treatment of malignant melanoma (IFN alfa 11 MU SC TIW in combination with the investigational melanoma vaccine melanoma theraccine 1.25 mL [I mL lysate + 0.25 mL vaccine adjuvant] given SC at weeks 1, 2, 3, 4, 8, 16, 24, 32, 40, and 48 and then every 8 weeks until week 104), and IFN-induced hypertriglyceridemia (gemfibrozil 600 mg PO BID). The patient had no history of cardiovascular or GI disease and was not receiving any concomitant medication. The possible mechanism of this potential IFN alfa-gemfibrozil interaction as related to the cytochrome P450 (CYP) enzyme system was assessed.
In this case of a possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID in a patient undergoing treatment for IFN-induced hypertriglyceridemia, the Naranjo Adverse Drug Reactions (ADR) Probability Scale score was 7 (ie, ADR possibly related to treatment).
Both IFN and gemfibrozil inhibit the activity of the hepatic enzymes CYP1A2 and CYP2C19. A possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID was reported in a patient undergoing treatment for IFN-induced hypertriglyceridemia.
在美国，高危II期或III期黑色素瘤患者术后常接受1年的辅助干扰素（IFN）治疗。与使用干扰素α-2b相关的不良事件主要是全身性症状。然而，已有报道出现需要治疗的高甘油三酯血症。
本报告旨在描述1例恶性黑色素瘤患者中干扰素α-2b与吉非贝齐之间潜在的药物相互作用，并探讨这种潜在相互作用的可能机制。
本报告介绍了1例43岁男性患者，体重101kg，新诊断为左臂III期黑色素瘤，已转移至锁骨上淋巴结。该患者在接受恶性黑色素瘤辅助治疗的第48周（共104周，治疗方案为皮下注射干扰素α 11MU，每周3次，联合研究性黑色素瘤疫苗melanoma theraccine 1.25mL[1mL裂解物+0.25mL疫苗佐剂]，分别在第1、2、3、4、8、16、24、32、40和48周皮下注射，之后每8周注射1次直至第104周）时，因严重胃肠道（GI）症状和肝酶浓度升高就诊于加利福尼亚州奥兰治的加州大学欧文医学中心，同时该患者存在干扰素诱导的高甘油三酯血症（口服吉非贝齐600mg，每日2次）。该患者无心血管或胃肠道疾病史，未同时服用任何其他药物。评估了这种潜在的干扰素α-吉非贝齐相互作用与细胞色素P450（CYP）酶系统相关的可能机制。
在1例接受干扰素诱导的高甘油三酯血症治疗的患者中，干扰素α 11MU每周3次与吉非贝齐600mg每日2次之间可能存在药物相互作用，根据Naranjo药物不良反应（ADR）概率量表评分，该评分结果为7分（即ADR可能与治疗相关）。
干扰素和吉非贝齐均可抑制肝酶CYP1A2和CYP2C19的活性。在1例接受干扰素诱导的高甘油三酯血症治疗的患者中，报告了干扰素α 11MU每周3次与吉非贝齐600mg每日2次之间可能存在药物相互作用。
