Drug–Drug Interactions of FXI Inhibitors: Clinical Relevance

Author:

Ferri Nicola123ORCID,Colombo Elisa34,Corsini Alberto34

Affiliation:

1. Department of Medicine, University of Padova, 35128 Padova, Italy

2. Veneto Institute of Molecular Medicine (VIMM), 35129 Padova, Italy

3. Coordinating Research Centre on Pharmacological Interactions, University of Milan, 20133 Milan, Italy

4. Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti”, University of Milan, 20133 Milan, Italy

Abstract

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug–drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.

Publisher

MDPI AG

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