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

Author:

Božina Nada12,Ganoci Lana2,Simičević Livija2,Gvozdanović Katarina3,Domjanović Iva Klarica3,Fistrek Prlić Margareta4,Križ Tena5,Borić Bilušić Ana3,Laganović Mario14,Božina Tamara6

Affiliation:

1. University of Zagreb School of Medicine , Zagreb , Croatia

2. University Hospital Centre Zagreb, Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics , Zagreb , Croatia

3. Croatian Agency for Medicinal Products and Medical Devices , Zagreb , Croatia

4. University Hospital Centre Zagreb, Department of Nephrology, Hypertension, Dialysis, and Transplantation , Zagreb , Croatia

5. University Hospital Centre “Sestre milosrdnice”, Department of Ophthalmology , Zagreb , Croatia

6. University of Zagreb School of Medicine, Department of Medical Chemistry, Biochemistry, and Clinical Chemistry , Zagreb , Croatia

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Public Health, Environmental and Occupational Health,Toxicology

Cited by 5 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. When the same treatment has different response: The role of pharmacogenomics in statin therapy;Biomedicine & Pharmacotherapy;2024-01

2. Topical Diclofenac-Induced Hepatotoxicity;Journal of Community Hospital Internal Medicine Perspectives;2023-05-10

3. UGT2B7 c.-161C>T polymorphism frequency in Croatian population;Archives of Industrial Hygiene and Toxicology;2022-12-01

4. Progression of precision statin prescribing for reduction of statin-associated muscle symptoms;Pharmacogenomics;2022-07

5. Multiple drugs interactions;Reactions Weekly;2021-07

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