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Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice

N.V Rajeshkumar, Shinichi Yabuuchi, Shweta G. Pai, Anirban Maitra, Manuel Hidalgo, Chi V. Dang
doi: https://doi.org/10.1101/2020.03.31.018556
N.V Rajeshkumar
1Department of Oncology, Pathology, Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
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  • For correspondence: rnv1@jhmi.edu cdang@licr.org
Shinichi Yabuuchi
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
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Shweta G. Pai
2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
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Anirban Maitra
3Sheikh Ahmed Center for Pancreatic Cancer Research, M.D. Anderson Cancer Center, Houston, TX
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Manuel Hidalgo
4Division of Hematology and Medical Oncology, Weill Department of Medicine, Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY
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Chi V. Dang
5Ludwig Institute for Cancer Research, New York, NY
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  • For correspondence: rnv1@jhmi.edu cdang@licr.org
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 04, 2020.
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Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice
N.V Rajeshkumar, Shinichi Yabuuchi, Shweta G. Pai, Anirban Maitra, Manuel Hidalgo, Chi V. Dang
bioRxiv 2020.03.31.018556; doi: https://doi.org/10.1101/2020.03.31.018556
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Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice
N.V Rajeshkumar, Shinichi Yabuuchi, Shweta G. Pai, Anirban Maitra, Manuel Hidalgo, Chi V. Dang
bioRxiv 2020.03.31.018556; doi: https://doi.org/10.1101/2020.03.31.018556

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