Drug-drug-gene interactions as mediators of adverse drug reactions to diclofenac and statins: a case report and literature review.
Arh Hig Rada Toksikol
; 72(3): 114-128, 2021 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-34187111
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pharmaceutical Preparations
/
Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Drug-Related Side Effects and Adverse Reactions
Limits:
Female
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Humans
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Middle aged
Language:
En
Journal:
Arh Hig Rada Toksikol
Year:
2021
Document type:
Article
Affiliation country: