Shaukat Aasma, Benekli Mustafa, Vladutiu Georgirene D, Slack James L, Wetzler Meir, Baer Maria R
School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
Ann Pharmacother. 2003 Jul-Aug;37(7-8):1032-5. doi: 10.1345/aph.1C467.
To report a case of rhabdomyolysis after concomitant use of simvastatin, a commonly used hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and fluconazole, an azole antifungal agent.
An 83-year-old white man with a history of congestive heart failure and hyperlipidemia presented to the hospital 1 week following the addition of fluconazole to a medication regimen that included simvastatin 40 mg once daily. The patient had severe muscle weakness and a markedly elevated serum creatine kinase activity, which resolved following discontinuation of simvastatin and fluconazole.
Rhabdomyolysis is a recognized adverse effect of HMG-CoA reductase inhibitors (statins), commonly caused by their interaction with other drugs, such as azole antifungals, that inhibit the cytochrome P450 isoenzyme family. An objective causality assessment revealed that the adverse drug event was probable. Although drug interactions have been described for combinations of other HMG-CoA reductase inhibitors and azole antifungals, rhabdomyolysis likely caused by the interaction between simvastatin and fluconazole has not yet been reported. This case reinforces the importance of being vigilant for drug interactions, particularly in connection with commonly prescribed medications such as statins.
Patients receiving statins who have cancer may receive azole antifungals and other drugs that inhibit CYP3A4 during treatment, predisposing them to toxicity. These patients should therefore be monitored closely for drug interactions.
报告一例在同时使用常用的羟甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂辛伐他汀和唑类抗真菌药氟康唑后发生横纹肌溶解的病例。
一名83岁白人男性,有充血性心力衰竭和高脂血症病史,在其每日一次服用40mg辛伐他汀的药物治疗方案中加用氟康唑1周后入院。患者出现严重肌无力,血清肌酸激酶活性显著升高,停用辛伐他汀和氟康唑后症状缓解。
横纹肌溶解是HMG-CoA还原酶抑制剂(他汀类药物)公认的不良反应,通常由其与其他抑制细胞色素P450同工酶家族的药物(如唑类抗真菌药)相互作用引起。客观因果关系评估显示该药物不良事件很可能发生。虽然已有其他HMG-CoA还原酶抑制剂与唑类抗真菌药联合使用时药物相互作用的报道,但辛伐他汀与氟康唑相互作用导致横纹肌溶解的情况尚未见报道。该病例强化了警惕药物相互作用的重要性,尤其是与他汀类等常用处方药相关的相互作用。
接受他汀类药物治疗的癌症患者在治疗期间可能会使用唑类抗真菌药和其他抑制CYP3A4的药物,从而使他们易发生毒性反应。因此,应对这些患者密切监测药物相互作用。