Kanathur N, Mathai M G, Byrd R P, Fields C L, Roy T M
Veterans Affairs Medical Center 111-B, PO Box 4000, Mountain Home, TN 37684-4000, USA.
Tenn Med. 2001 Sep;94(9):339-41.
Simvastatin, a hydroxymethyl glutarate coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used cholesterol lowering agent. The long-term safety profile of simvastatin, established over ten-years of clinical use, is excellent. Both rhabdomyolysis and hepatitis, however, are recognized toxic effects of this medication, and generally occur when the patients are taking more than 40 mg of simvastatin a day. Potent inhibitors of the cytochrome P450 3A4 (CYP3A4) enzyme increase the incidence of simvastatin toxicity. Calcium channel blockers are weak inhibitors of the CYP3A4 enzyme. Diltiazem is known to increase the serum concentration of simvastatin. Many patients who take both simvastatin and diltiazem require lower doses of simvastatin to achieve the recommended reduction in cholesterol. Since diltiazem is known to increase plasma levels of lovastatin, a similar phenomenon may occur with simvastatin. Our patient had been stable for three years on simvastatin therapy. His rhabdomyolysis and hepatitis coincided with the addition of diltiazem. This is the first report of the combined toxicities of rhabdomyolysis and hepatitis being induced by the addition of diltiazem to simvastatin therapy. This patient serves as a reminder to the clinician of the potential interaction of these two commonly used drugs.
辛伐他汀是一种羟甲基戊二酸单酰辅酶A（HMG-CoA）还原酶抑制剂，是常用的降胆固醇药物。经过十年临床应用确立的辛伐他汀长期安全性良好。然而，横纹肌溶解症和肝炎都是该药物公认的毒性作用，通常发生在患者每日服用辛伐他汀超过40毫克时。细胞色素P450 3A4（CYP3A4）酶的强效抑制剂会增加辛伐他汀毒性的发生率。钙通道阻滞剂是CYP3A4酶的弱抑制剂。已知地尔硫䓬会增加辛伐他汀的血清浓度。许多同时服用辛伐他汀和地尔硫䓬的患者需要降低辛伐他汀剂量以达到推荐的胆固醇降低水平。由于已知地尔硫䓬会增加洛伐他汀的血浆水平，辛伐他汀可能会出现类似现象。我们的患者接受辛伐他汀治疗三年来病情一直稳定。他的横纹肌溶解症和肝炎与加用地尔硫䓬同时出现。这是关于在辛伐他汀治疗中加用地尔硫䓬导致横纹肌溶解症和肝炎联合毒性的首例报告。该患者提醒临床医生注意这两种常用药物之间的潜在相互作用。
