RT Journal Article
SR Electronic
T1 Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.31.018556
DO 10.1101/2020.03.31.018556
A1 N.V Rajeshkumar
A1 Shinichi Yabuuchi
A1 Shweta G. Pai
A1 Anirban Maitra
A1 Manuel Hidalgo
A1 Chi V. Dang
YR 2020
UL http://biorxiv.org/content/early/2020/04/04/2020.03.31.018556.abstract
AB Guided by the principle of primum non nocere (first do no harm), we report a cautionary note on the potential fatal toxicity of chloroquine (CQ) or hydroxychloroquine (HCQ) in combination with anti-diabetic drug metformin. We observed that the combination of CQ or HCQ and metformin, which were used in our studies as potential anti-cancer drugs, killed 30-40% of mice. While our observations in mice may not translate to toxicity in humans, the reports that CQ or HCQ has anti-COVID-19 activity, the use of CQ resulting in toxicity and at least one death, and the recent Emergency Use Authorization (EUA) for CQ and HCQ by the US Food and Drug Administration (FDA) prompted our report. Here we report the lethality of CQ or HCQ in combination with metformin as a warning of its potential serious clinical toxicity. We hope that our report will be helpful to stimulate pharmacovigilance and monitoring of adverse drug reactions with the use of CQ or HCQ, particularly in combination with metformin.