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

  • Nada Božina Klinički bolnički centar Zagreb, Klinički zavod za laboratorijsku dijagnostiku
  • Lana Ganoci Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb https://orcid.org/0000-0003-3898-4554
  • Livija Simicevic Division of Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb https://orcid.org/0000-0002-2491-1920
  • Katarina Gvozdanovic Croatian Agency for Medicinal Products & Medical Devices, Zagreb, Croatia https://orcid.org/0000-0002-7943-3030
  • Iva Klarica Domjanovic Croatian Agency for Medicinal Products & Medical Devices, Zagreb, Croatia https://orcid.org/0000-0001-5488-5893
  • Margareta Fistrek Prlic Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Croatia https://orcid.org/0000-0002-9169-2190
  • Tena Kriz Department of Ophthalmology, University Hospital Centre 'Sestre milosrdnice', Zagreb, Croatia
  • Ana Boric Bilusic Croatian Agency for Medicinal Products & Medical Devices, Zagreb, Croatia
  • Mario Laganovic Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Croatia https://orcid.org/0000-0002-0240-4178
  • Tamara Bozina Department of Medical Chemistry, Biochemistry & Clinical Chemistry, School of Medicine, University of Zagreb, Croatia. https://orcid.org/0000-0001-5883-7979
Keywords: drug interactions, hepatotoxicity, myotoxicity, nephrotoxicity, pharmacogenetics

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.

Published
2021-06-07
How to Cite
1.
Božina N, Ganoci L, Simicevic L, Gvozdanovic K, Klarica Domjanovic I, Fistrek Prlic M, Kriz T, Boric Bilusic A, Laganovic M, Bozina T. Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review. Arh Hig Rada Toksikol [Internet]. 2021Jun.7 [cited 2021Jul.31];72(2). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/1405
Section
Review