s-1743 and Arrhythmias--Cardiac

Recent results from data mining analyses and reports of adverse drug events suggest a QT-prolonging drug-drug interaction resulting from the combination of distinct proton pump inhibitors and cephalosporins. Therefore, this study aimed at investigating the effect of the suspected QT-prolonging combinations of lansoprazole + ceftriaxone and esomeprazole + cefazolin, respectively. 26 hearts of New Zealand White rabbits were retrogradely perfused and paced at different cycle lengths. After generating baseline data, the hearts were assigned to two groups: In group 1, hearts were treated with 5 µM lansoprazole. Thereafter, 200 µM ceftriaxone was infused additionally. Group 2 was perfused with 10 µM esomeprazole followed by 250 µM cefazolin. In group 1, lansoprazole did not significantly alter QT intervals and APD

Topics: Action Potentials; Animals; Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Ceftriaxone; Drug Interactions; Esomeprazole; Female; Heart Conduction System; Heart Rate; Isolated Heart Preparation; Lansoprazole; Proton Pump Inhibitors; Rabbits; Refractory Period, Electrophysiological; Risk Assessment; Time Factors

We report a case of ventricular bigeminy with concomitant administration of methadone, voriconazole and esomeprazole in a Caucasian woman aged 26 with acute lymphoblastic leukaemia. Plasma concentrations of voriconazole and methadone were high, 12.4 mg/l (therapeutic range: 1-4 mg/l) and 1.6 mg/l (therapeutic range: 0.2-0.4 mg/l), respectively. In the absence of esomeprazole, no more episode of cardiac arrhythmia occurred and 7 days after, methadone plasma concentration fell at 0.57 ml/l while voriconazole concentration was at 5.5 mg/l. We speculate that a pharmacokinetic interaction between methadone and voriconazole was amplified by the addition of esomeprazole. This led to the large increase of the plasma concentration of methadone and was potentially responsible for its cardiac toxicity.. Physicians should be aware of the potential interaction between voriconazole, esomeprazole and methadone leading to arrhythmia. The inhibitory potential of voriconazole is possibly increased by esomeprazole.

Topics: Adult; Analgesics, Opioid; Antifungal Agents; Arrhythmias, Cardiac; Drug Interactions; Esomeprazole; Female; Humans; Methadone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Proton Pump Inhibitors; Pyrimidines; Triazoles; Ventricular Dysfunction; Voriconazole