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. 2020 Jul;43(7):657-660.
doi: 10.1007/s40264-020-00955-y.

A New Drug-Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study

Jean-Louis Montastruc  1 , Pierre-Louis Toutain  2   3
Affiliations

A New Drug-Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study

Jean-Louis Montastruc et al. Drug Saf. 2020 Jul.

Abstract

Introduction: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice.

Objective: The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data.

Methods: Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval.

Results: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8).

Conclusion: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.

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Conflict of interest statement

The authors declare that they have no competing interests.

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References

    1. Vinetz JM. Chemotherapy of malaria. In: Brunton LL, Hilal-Dandan R, Knollmann BJ, editors. Goodman and Gilman’s the pharmacological basis of therapeutics. 13. New York: McGraw Hill; 2018. pp. 968–986.
    1. Moore N. Chloroquine for COVID-19 infection. Drug Saf. 2020 doi: 10.1007/s40264-020-00933-4. - DOI - PMC - PubMed
    1. Roustit M, Guilhaumou R, Molimard M, Milou Drici M, Laporte S, Montastruc JL, On behalf of the French Society of Pharmacology and Therapeutics (SFPT) Chloroquine and hydroxychloroquine in the management of COVID-19: much kerfuffle but little evidence. Therapie. 2020 doi: 10.1016/j.therap.2020.05.010Reference. - DOI - PMC - PubMed
    1. Lenzer J. Covid-19: US gives emergency approval to hydroxychloroquine despite lack of evidence. BMJ. 2020;369:m1335. doi: 10.1136/bmj.m1335. - DOI - PubMed
    1. Rajeshkumar NV, Yabuuchi S, Pai SG, Maitra A, Hidalgo M, Dang CV. Fatal toxicity of chloroquine or hydroxychloroquine with metformin in mice. Biorxiv. 2020 doi: 10.1101/2020.03.31.018556. - DOI

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