Colchicine-induced rhabdomyolysis following a concomitant use of clarithromycin in a haemodialysis patient with familial Mediterranean fever.
Colchicine-induced rhabdomyolysis following a concomitant use of clarithromycin in a haemodialysis patient with familial Mediterranean fever.
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DOI：
10.1093/ckj/sft129
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发表时间：
2013-12
影响因子：
4.6
通讯作者：
Keven K
中科院分区：
文献类型：
--
作者：
Çelebi ZK;Akturk S;Oktay EI;Duman N;Keven K
讨论继发于FMF的淀粉样变性导致ESRD后，大多数患者仍需要继续使用秋水仙碱以预防FMF发作，并延缓组织中淀粉样蛋白沉积的进展，特别是肾脏。通常的预防剂量为0.5 mg，每日1 - 3次，建议老年人、儿童和肝肾衰竭患者减少剂量[3]。秋水仙碱主要在肝脏中通过CYP 3A 4代谢，是P-糖蛋白转运蛋白（也称为多药物转运蛋白1和ATP结合盒B1转运蛋白）的底物。P-糖蛋白与药物从细胞中流出有关，秋水仙碱的排泄主要依赖于P-糖蛋白。秋水仙碱的尿排泄率约为10- 20%，建议肾衰竭患者常规减量[2-4]。因此，许多临床医生减少透析患者的秋水仙碱剂量，以避免毒性，而不完全停止。CYP 3A 4抑制剂（如地尔硫卓、大环内酯类抗生素、三唑类等）增加秋水仙碱的毒性[2-4]。大环内酯类也是P-糖蛋白的抑制剂，其可进一步损害秋水仙碱消除，这已被充分报道[5-7]。此外，在联合使用秋水仙碱和HMG-CoA还原酶抑制剂的患者中也报告了严重的相互作用，其中肌肉症状（包括虚弱和疼痛）是主要的初步结果[6]。
DiscussionAfter development of ESRD due to amyloidosis secondary to FMF, most patients still need to continue colchicine to prevent FMF attacks and also retard the progression of amyloid deposition in the tissues, especially of the kidneys. The usual prophylactic dose is 0.5 mg once to thrice daily, and dose reductions are suggested for elderly, children and liver and renal failure patients [3]. Colchicine is mainly metabolized in the liver by CYP3A4 and is a substrate for the P-glycoprotein transporter (also known as multidrug transporter 1 and ATP-binding cassette B1 transporter). P-glycoprotein is associated with drug efflux from cells and colchicine excretion is largely dependent on P-glycoprotein. Urinary excretion of colchicine is about 10–20%, and a routine dose reduction is recommended for renal failure patients [2–4]. Therefore, many clinicians reduce the dose of colchicine for dialysis patients to avoid toxicity without complete cessation. Inhibitors of CYP3A4 (such as diltiazem, macrolide antibiotics, triazoles, etc.) increase the toxicity of colchicine [2–4]. Macrolides are also inhibitors of P-glycoproteins which can further impair colchicine elimination which is well reported [5–7]. Moreover, severe interactions have also been reported in patients using a combination of colchicine and HMG-CoA reductase inhibitors in which muscle symptoms, including weakness and pain, are the main initial findings [6].