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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1418997

Interactions of Warfarin with COVID-19 Vaccine/Drugs, Monoclonal Antibodies, and Targeted Anticancer Agents from Real-World Data Mining

Provisionally accepted
Yan Gao Yan Gao 1Qingsong Huang Qingsong Huang 1Jun Li Jun Li 2Junsheng He Junsheng He 2Fang Qian Fang Qian 1Juanjuan Yi Juanjuan Yi 2,3*
  • 1 Shanghai Jiading District Hospital of Traditional Chinese Medicine, Shanghai, China
  • 2 City University of Hong Kong, Kowloon, Hong Kong, SAR China
  • 3 Department of Infectious Diseases and Public Health, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, SAR China

The final, formatted version of the article will be published soon.

    Objective:This study aims to examine the unresolved drug-drug interactions of warfarin using realworld data.Methods: Electronic medical records from a hospital in Shanghai, China, were used to summarize drug-related problems (DRPs) among inpatients taking warfarin in 2022. Additionally, adverse event data for warfarin from January 2004 to December 2023 were extracted from the U.S. adverse event reporting system to evaluate the bleeding risk associated with the concomitant use of warfarin and COVID-19 Vaccine/drugs, monoclonal antibodies, and targeted anticancer agents.The electronic clinical records yielded 180 cases, of which 130 cases (72.22%) had 276 DRPs identified. DRP5 (n = 172, 64.13%) was identified as the most common issue, comprising 145 drug interactions and 27 adverse drug reactions (ADRs). The analyses of warfarin ADR records (n = 53709) from the database revealed that tocilizumab (adjusted Odds Ratio (aOR): 3.39[95% CI: 1.77-7.03]; P < 0.001), ibrutinib (aOR: 2.53[1.61-4.19]; P < 0.001), and cabozantinib (aOR: 3.34[1.40-9.85]; P = 0.013) significantly increased the risk of warfarin bleeding. In contrast, nirmatrelvir-ritonavir (aOR: 0.32[0.14-0.69]; P = 0.004), adalimumab (aOR: 0.72[0.56-0.93]; P = 0.012), golimumab (aOR: 0.18[0.05-0.50]; P = 0.02), tofacitinib (aOR: 0.51[0.29-0.86]; P = 0.013), and dabrafenib (aOR: 0.17[0.04-0.55]; P = 0.007) significantly reduced the risk of bleeding when combined with warfarin. Remdesivir combined with warfarin was associated with a statistically significant increase in bleeding events (P = 0.047); while the risk was not significant after adjusting for age and sex (aOR: 1.79; P = 0.2). No significant effect was observed with the COVID-19 vaccine (aOR: 0.89; P = 0.8).Drug-drug interactions contribute to the adverse effects of warfarin. This study provides real-world evidence of newly identified drug interactions with warfarin. It reminds clinicians to monitor INR and adjust warfarin doses accordingly when used in combination with these medications.

    Keywords: DRP, ADR, Warfarin, VKA, DDI, bleeding, Safety, risk

    Received: 23 Apr 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Gao, Huang, Li, He, Qian and Yi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Juanjuan Yi, City University of Hong Kong, Kowloon, Hong Kong, SAR China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.