Piquette R K
Department of Pharmaceutical Services, Ottawa Hospital, Ontario, Canada.
Ann Pharmacother. 1999 Jan;33(1):22-6. doi: 10.1345/aph.18107.
To highlight a case of torsade de pointes ventricular arrhythmia induced by the concomitant use of cisapride and clarithromycin.
A 77-year-old white woman was admitted to the hospital with a diagnosis of pneumonia and exacerbation of congestive heart failure. In addition to her usual medications, which included cisapride, the patient was prescribed trimethoprim/sulfamethoxazole and clarithromycin for pneumonia. Within 48 hours, the patient had documented episodes of symptomatic torsade de pointes arrhythmia, which eventually responded to therapy. Both cisapride and clarithromycin were discontinued, and the patient did not have any recurring episodes during a 32-month follow-up.
Cisapride has been implicated in causing adverse cardiac events, including torsade de pointes arrhythmia. In most cases, the patients had preexisting risk factors for torsade de pointes and/or were receiving other medications known to inhibit the hepatic CYP3A4 enzyme system and the metabolism of cisapride. There is evidence that clarithromycin, a relatively new macrolide antibiotic, also inhibits the isoenzyme CYP3A4. The resulting accumulation of cisapride caused by concomitant clarithromycin therapy was believed to have been the cause of the torsade de pointes arrhythmia in this patient.
Concomitant use of cisapride and clarithromycin may cause torsade de pointes arrhythmia.
强调一例因同时使用西沙必利和克拉霉素诱发尖端扭转型室性心律失常的病例。
一名77岁白人女性因肺炎和充血性心力衰竭加重入院。除了常用药物（包括西沙必利）外，该患者因肺炎还被处方了甲氧苄啶/磺胺甲恶唑和克拉霉素。在48小时内，患者记录到有症状的尖端扭转型心律失常发作，最终对治疗有反应。西沙必利和克拉霉素均停药，在32个月的随访期间患者未出现任何复发发作。
西沙必利已被认为可导致不良心脏事件，包括尖端扭转型心律失常。在大多数情况下，患者存在尖端扭转型心律失常的既往危险因素和/或正在接受其他已知可抑制肝脏CYP3A4酶系统及西沙必利代谢的药物。有证据表明，相对较新的大环内酯类抗生素克拉霉素也抑制同工酶CYP3A4。据信，克拉霉素联合治疗导致的西沙必利蓄积是该患者尖端扭转型心律失常的原因。
西沙必利和克拉霉素同时使用可能会导致尖端扭转型心律失常。
