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Clin Pharmacol Ther ; 108(5): 1090-1097, 2020 11.
Article in English | MEDLINE | ID: covidwho-615066

ABSTRACT

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.


Subject(s)
Azithromycin , Coronavirus Infections , Drug Monitoring , Electrocardiography/methods , Hydroxychloroquine , Long QT Syndrome , Pandemics , Pneumonia, Viral/drug therapy , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Anti-Infective Agents/pharmacokinetics , Azithromycin/administration & dosage , Azithromycin/adverse effects , Azithromycin/pharmacokinetics , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/physiopathology , Dimensional Measurement Accuracy , Drug Monitoring/instrumentation , Drug Monitoring/methods , Drug Monitoring/standards , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Hydroxychloroquine/pharmacokinetics , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Male , Middle Aged , Outcome Assessment, Health Care , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Torsades de Pointes/chemically induced , Torsades de Pointes/prevention & control , COVID-19 Drug Treatment
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