Key result
Pharmacogenetic variants significantly alter DOAC pharmacokinetics and increase risk of adverse drug reactions.
Why the study?
Given the widespread use of DOACs and their variable pharmacokinetics, exploring pharmacogenetics is critical to optimize dosing and mitigate the risk of serious adverse drug reactions.
Does pharmacogenetic profiling prevent adverse drug reactions in patients receiving direct oral anticoagulants?
Does pharmacogenetic profiling prevent adverse drug reactions in patients receiving direct oral anticoagulants?
Integrating pharmacogenetic data could allow for personalized DOAC dosing, maximizing efficacy while minimizing serious bleeding complications.
Hypothesis-generating for pharmacogenetic-guided DOAC dosing; prospective trials needed before clinical adoption.
Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.
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Shnayder et al. (2021) conducted a review in High risk of thromboembolism requiring anticoagulant therapy. Direct oral anticoagulants (DOACs) and pharmacogenetics was evaluated. Genetic variants in genes encoding biotransformation enzymes and transporters significantly affect the pharmacokinetics of direct oral anticoagulants and the risk of adverse drug reactions.
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