Concentration-dependent mortality of chloroquine in overdose
Open Access
- 8 July 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
Hydroxychloroquine and chloroquine are used extensively in malaria and rheumatological conditions, and now in COVID-19 prevention and treatment. Although generally safe they are potentially lethal in overdose. In-vitro data suggest that high concentrations and thus high doses are needed for COVID-19 infections, but as yet there is no convincing evidence of clinical efficacy. Bayesian regression models were fitted to survival outcomes and electrocardiograph QRS durations from 302 prospectively studied French patients who had taken intentional chloroquine overdoses, of whom 33 died (11%), and 16 healthy volunteers who took 620 mg base chloroquine single doses. Whole blood concentrations of 13.5 µmol/L (95% credible interval 10.1–17.7) were associated with 1% mortality. Prolongation of ventricular depolarization is concentration-dependent with a QRS duration >150 msec independently highly predictive of mortality in chloroquine self-poisoning. Pharmacokinetic modeling predicts that most high dose regimens trialled in COVID-19 are unlikely to cause serious cardiovascular toxicity.Keywords
Funding Information
- Wellcome Trust (Principal Research Fellowship 093956/Z/10/C)
This publication has 50 references indexed in Scilit:
- Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosusEP Europace, 2013
- Chloroquine cardiomyopathy – a review of the literatureImmunopharmacology and Immunotoxicology, 2013
- Blood concentrations are better predictors of chioroquine poisoning severity than plasma concentrations: a prospective study with modeling of the concentration/effect relationshipsClinical Toxicology, 2010
- Emergency feasibility in medical intensive care unit of extracorporeal life support for refractory cardiac arrestIntensive Care Medicine, 2007
- Chloroquine poisoning in Zimbabwe: a toxicoepidemiological studyJournal of Applied Toxicology, 2002
- Treatment of acute chloroquine poisoningCritical Care Medicine, 1996
- Hypokalaemia related to acute chloroquine ingestionThe Lancet, 1995
- Treatment of Severe Chloroquine PoisoningNew England Journal of Medicine, 1988
- Animal toxicity and pharmacokinetics of hydroxychloroquine sulfateAmerican Journal Of Medicine, 1983
- The treatment of hepatic amebiasis with chloroquineAmerican Journal Of Medicine, 1949