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Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review Cover

Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review

Open Access
|Jun 2021

Abstract

Concomitant treatment with drugs that inhibit drug metabolising enzymes and/or transporters, such as commonly prescribed statins and nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated with prolonged drug exposure and increased risk of adverse drug reactions (ADRs) due to drug-drug interactions. The risk is further increased in patients with chronic diseases/comorbidities who are more susceptible because of their genetic setup or external factors. In that light, we present a case of a 46-year-old woman who had been experiencing acute renal and hepatic injury and myalgia over two years of concomitant treatment with diclofenac, atorvastatin, simvastatin/fenofibrate, and several other drugs, including pantoprazole and furosemide. Our pharmacogenomic findings supported the suspicion that ADRs, most notably the multi-organ toxicity experienced by our patient, may be owed to drug-drug-gene interactions and increased bioavailability of the prescribed drugs due to slower detoxification capacity and decreased hepatic and renal elimination. We also discuss the importance of CYP polymorphisms in the biotransformation of endogenous substrates such as arachidonic acid and their modulating role in pathophysiological processes. Yet even though the risks of ADRs related to the above mentioned drugs are substantially evidenced in literature, pre-emptive pharmacogenetic analysis has not yet found its way into common clinical practice.

DOI: https://doi.org/10.2478/aiht-2021-72-3549 | Journal eISSN: 1848-6312 | Journal ISSN: 0004-1254
Language: English, Croatian, Slovenian
Page range: 114 - 128
Submitted on: Apr 1, 2021
Accepted on: May 1, 2021
Published on: Jun 28, 2021
Published by: Institute for Medical Research and Occupational Health
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2021 Nada Božina, Lana Ganoci, Livija Simičević, Katarina Gvozdanović, Iva Klarica Domjanović, Margareta Fistrek Prlić, Tena Križ, Ana Borić Bilušić, Mario Laganović, Tamara Božina, published by Institute for Medical Research and Occupational Health
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.