Gooderham M J, Bolli P, Fernandez P G
University of Western Ontario, London, Canada.
Ann Pharmacother. 1999 Jul-Aug;33(7-8):796-9. doi: 10.1345/aph.18330.
To report a case of a clarithromycin-associated warfarin interaction and digoxin toxicity in a patient.
A 72-year-old white woman with chronic atrial fibrillation receiving long-standing therapy with digoxin 0.25 mg/d and warfarin 22.5 mg/wk was prescribed clarithromycin 500 mg three times daily for eradication of Helicobacter pylori. The patient presented to the emergency department with gastrointestinal symptoms, weakness, dizziness, and visual changes 12 days after initiation of clarithromycin. Laboratory results revealed a serum digoxin concentration of 4.6 ng/mL (normal 1.0-2.6) and an international normalized ratio of 7.3 (2.0-3.0). Digoxin, warfarin, and clarithromycin were discontinued and the patient was admitted to the hospital for treatment to resolve the symptoms and to return laboratory values to a safe range. Reduced dosages of digoxin (0.125 mg/d) and warfarin (17.5 mg/wk) were restarted on day 7 of hospitalization. The patient was discharged on day 11 in good condition.
Several reports of clarithromycin-induced drug interactions with digoxin and with warfarin have been published. Previously, case reports of macrolide-associated interactions mainly involved erythromycin, but more recently have implicated clarithromycin. The interaction between clarithromycin and warfarin is thought to occur from an inhibition of the cytochrome P450 drug metabolizing system. Clarithromycin is thought to cause digoxin toxicity by an alteration of the digoxin-metabolizing gut flora, thereby causing an increase in the digoxin concentration in susceptible individuals. Drug interactions can occur by different mechanisms in the same patient.
Potential drug interactions can occur between commonly prescribed medications. It is important to monitor patients for symptoms and alterations in laboratory values to prevent not only serious complications, but also unnecessary hospitalizations.
报告1例患者中克拉霉素与华法林相互作用及地高辛中毒的病例。
一名72岁白人女性，患有慢性心房颤动，长期接受地高辛0.25mg/d和华法林22.5mg/周治疗，为根除幽门螺杆菌，给予克拉霉素500mg每日3次。开始使用克拉霉素12天后，患者因出现胃肠道症状、乏力、头晕和视力变化就诊于急诊科。实验室检查结果显示血清地高辛浓度为4.6ng/mL（正常范围1.0 - 2.6），国际标准化比值为7.3（2.0 - 3.0）。停用了地高辛、华法林和克拉霉素，患者入院治疗以缓解症状并使实验室检查值恢复到安全范围。住院第7天重新开始使用剂量减少的地高辛（0.125mg/d）和华法林（17.5mg/周）。患者于第11天康复出院。
已有多篇关于克拉霉素与地高辛及华法林药物相互作用的报道。此前，大环内酯类药物相关相互作用的病例报告主要涉及红霉素，但最近也涉及到克拉霉素。克拉霉素与华法林之间的相互作用被认为是由于抑制细胞色素P450药物代谢系统所致。克拉霉素被认为通过改变地高辛代谢的肠道菌群导致地高辛中毒，从而使易感个体的地高辛浓度升高。在同一患者中，药物相互作用可能通过不同机制发生。
常用药物之间可能发生潜在的药物相互作用。监测患者的症状和实验室检查值变化非常重要，这不仅可以预防严重并发症，还能避免不必要的住院治疗。
