Drug–Drug Interactions in the Treatment of Cancer-Associated Venous Thromboembolism with Direct Oral Anticoagulants

Abstract

Venous thromboembolism (VTE) is a frequent complication of cancer, and management of cancer-associated thrombosis (CAT) is challenging due to increased risks of bleeding and recurrent VTE. Recent trials have shown an acceptable efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of CAT compared to low-molecular weight heparin. Although DOACs provide an effective and convenient treatment option in CAT, the need to assess the risk of drug–drug interactions (DDI) with antineoplastic therapies poses a barrier to their use in clinical practice. With the aim of supporting the assessment of CAT patients for treatment with DOAC, this review provides a comprehensive overview of the compatibility of antineoplastic therapies with the individual DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban). Using several data sources, we characterized 100 widely used antineoplastic agents with regard to their effect on p-glycoprotein and cytochrome P450, both important in the transport and elimination of DOACs. This enabled us to evaluate 400 “DOAC-antineoplastic agent”-pairs regarding their likelihood to interact (unlikely, potential, or likely), ultimately leading to clinical recommendations on the appropriateness of concomitant use for each pair. A potential or likely DDI was identified for 12% of the evaluated pairs. For nearly all antineoplastic agents, at least one DOAC was considered compatible.

2024 Eberhard F. Mammen Award Announcements: Part I—Most Popular Articles

“…Consequently, the most popular papers from each category are identified separately. Tables 3 and 4 respectively list the top 25 downloaded articles from STH in 2023 (from 2022 and 2023 inclusive), as eligible for either the “free access” ( Table 3 ) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 or “general category” ( Table 4 ) 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 awards.…”

“…The publisher of STH, Thieme, had in the past provided most material related to COVID-19 as free to download, and so COVID19-related material is less likely to be itemized in the “general category” list of most popular. 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 The 25 most popular non-free to download papers are listed in Table 4 . The first two papers listed are the official winners of the 2024 Most Popular in the general category.…”

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients—A Review

“…Other groups are small-molecule inhibitors [119], monoclonal antibodies i.e., alemtuzumab, hormonal agents, i.e., enzalutamide, and immune-modulating agents, i.e., cyclosporine [118]. It is important to highlight that DOACs will interfere differently with antineoplastic agents, with apixaban having the lowest potential to interact with antineoplastic agents [120]. There is still a lot of research to be done to investigate possible drug-drug interactions.…”

Cancer-Associated Thrombosis and Beyond: Biomarkers, Treatments, and Cancer-Hemostasis Interactions

“…The issue is concluded with an extensive work by Hellfritzsch et al evaluating possible interactions between DOACs and antineoplastic agents. 23 This has been a concern with many CAT patients and their caregivers. Unfortunately, there are not many in vivo interaction studies in this field, and therefore some guidelines have recommended a cautious approach.…”