Review article

https://doi.org/10.2478/aiht-2021-72-3549

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

Nada Božina orcid.org/0000-0001-6016-1699 ; 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
Lana Ganoci ; University Hospital Centre Zagreb, Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, Zagreb, Croatia
Livija Simičević orcid.org/0000-0002-2491-1920 ; University Hospital Centre Zagreb, Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, Zagreb, Croatia
Katarina Gvozdanović ; Croatian Agency for Medicinal Products and Medical Devices, Zagreb, Croatia
Iva Klarica Domjanović ; Croatian Agency for Medicinal Products and Medical Devices, Zagreb, Croatia
Margareta Fistrek Prlić ; University Hospital Centre Zagreb, Department of Nephrology, Hypertension, Dialysis, and Transplantation, Zagreb, Croatia
Tena Križ ; University Hospital Centre “Sestre milosrdnice”, Department of Ophthalmology, Zagreb, Croatia
Ana Borić Bilušić ; Croatian Agency for Medicinal Products and Medical Devices, Zagreb, Croatia
Mario Laganović orcid.org/0000-0002-0240-4178 ; University of Zagreb School of Medicine, Zagreb, Croatia, 4 University Hospital Centre Zagreb, Department of Nephrology, Hypertension, Dialysis, and Transplantation, Zagreb, Croatia
Tamara Božina orcid.org/0000-0001-5883-7979 ; University of Zagreb School of Medicine, Department of Medical Chemistry, Biochemistry, and Clinical Chemistry, Zagreb, Croatia

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.

Keywords

drug interactions; hepatotoxicity; myotoxicity; nephrotoxicity; pharmacogenetics

Hrčak ID:

258902

URI

https://hrcak.srce.hr/258902

Publication date:

15.6.2021.

Article data in other languages: croatian

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