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

Montastruc, J L; Toutain, P L

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.

Citation

Montastruc, J. L., & Toutain, P. L. (2020). A New Drug–Drug Interaction Between Hydroxychloroquine and Metformin? A Signal Detection Study. Drug Safety, 43(7), 657-660. https://doi.org/10.1007/s40264-020-00955-y

• Journal Article Type: Article
• Acceptance Date: Jun 2, 2020
• Publication Date: Jun 3, 2020
• Deposit Date: Sep 4, 2020
• Publicly Available Date: Jun 4, 2021
• Journal: Drug Safety
• Print ISSN: 0114-5916
• Publisher: Springer
• Peer Reviewed: Peer Reviewed
• Volume: 43
• Issue: 7
• Pages: 657-660
• DOI: https://doi.org/10.1007/s40264-020-00955-y
• Public URL: https://rvc-repository.worktribe.com/output/1377154
• Publisher URL: https://doi.org/10.1007/s40264-020-00955-y