Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions

Abstract

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.

Direct Oral Anticoagulants (DOAC): Are We Ready for a Pharmacogenetic Approach?

“…Similarly, other recent studies have confirmed the correlation between ABCB1 and CES1 SNPs and plasma levels of dabigatran in Chinese patient populations [14]. Recent additional reviews of literature do not add much to what has been previously described [15,16].…”

Cutaneous Ulcer Caused by Apixaban Treatment Is Resolved after Replacement with Dabigatran

“…apixaban is also a substrate of P-gp transport proteins and breast cancer resistance protein (BCRP). Cytochrome P450 (especially CYP3A4/5) [ 40 , 41 ] and advanced age represent two of the contributing factors to the reduction in cytochrome P450 functionality [ 42 ]. However, we cannot exclude that an overexpression or an increase in CYP3A4/5 activity (on a genetic basis) significantly may have reduced apixaban levels in our patient, by inducing vascular thromboembolic microphenomena downstream.…”

The role of direct oral anticoagulants in the era of COVID-19: are antiviral therapy and pharmacogenetics limiting factors?

“…The pharmacogenetics of DOACs affect their pharmacokinetic properties. Interindividual variability regarding the efficacy and safety profile of direct anticoagulants could be related to polymorphism of the genes responsible for pharmacokinetic processes (17). To date, several single nucleotide polymorphisms (SNPs) of genes coding the proteins participating in the metabolism of DOACs have been correlated with anticoagulant treatment response.…”