Proceedings of the 13th International Conference on Thrombosis and Hemostasis Issues in Cancer, 2026
Vol. 5 No. s1 (2026)
Pharmacokinetic interactions between anticancer drugs and direct oral anticoagulants: clinical implications for safe anticoagulation
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 16 April 2026
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Patients with cancer have an increased risk of thrombosis requiring anticoagulation. Direct oral anticoagulants have become the primary anticoagulant of choice in most patients with cancer. Patients with cancer also receive many concomitant medications, including anticancer therapies with potential risks of drug-drug interactions with anticoagulants that can lead to concerns of bleeding or recurrent thrombosis. The best management strategies remain unclear. In this article, we aim to review the available literature pertaining to pharmacokinetic interactions between anticancer therapies and direct oral anticoagulants and provide guidance based on the evidence.
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1. Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018;378:615-24. DOI: https://doi.org/10.1056/NEJMoa1711948
2. Young AM, Marshall A, Thirlwall J, et al. Comparison of an oral factor Xa Inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018;36:2017-23. DOI: https://doi.org/10.1200/JCO.2018.78.8034
3. Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020;382:1599-607. DOI: https://doi.org/10.1056/NEJMoa1915103
4. Frere C, Farge D, Schrag D, et al. Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials. J Hematol Oncol 2022;15:69. DOI: https://doi.org/10.1186/s13045-022-01289-1
5. Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019;380:711-9. DOI: https://doi.org/10.1056/NEJMoa1814468
6. Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019;380:720-8. DOI: https://doi.org/10.1056/NEJMoa1814630
7. Delluc A, Wang TF, Yap ES, et al. Anticoagulation of cancer patients with non-valvular atrial fibrillation receiving chemotherapy: guidance from the SSC of the ISTH. J Thromb Haemost 2019;17:1247-52. DOI: https://doi.org/10.1111/jth.14478
8. Khorana AA, Noble S, Lee AYY, et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018;16:1891-4. DOI: https://doi.org/10.1111/jth.14219
9. Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO guideline update. J Clin Oncol 2023;41:3063-71. DOI: https://doi.org/10.1200/JCO.23.00294
10. Lyman GH, Carrier M, Ay C, et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv 2021;5927-74.
11. Farge D, Frere C, Connors JM, et al. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 2019;20e566-e81. DOI: https://doi.org/10.1016/S1470-2045(19)30750-8
12. Lees J, Chan A. Polypharmacy in elderly patients with cancer: clinical implications and management. Lancet Oncol 2011;12:1249-57. DOI: https://doi.org/10.1016/S1470-2045(11)70040-7
13. Daiichi Sankyo, Inc. Savaysa (edoxaban) prescribing information. Basking Ridge, Daiichi Sankyo, Inc.; 2024.
14. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013;369:507-16. DOI: https://doi.org/10.1056/NEJMoa1306220
15. Patel SH, George TL, Wang TF, et al. Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low-molecular-weight heparin. Cancer 2021;127:938-45. DOI: https://doi.org/10.1002/cncr.33337
16. Vrotniakaite-Bajerciene K, Tsang C, Wang TF, Carrier M. Drug-drug interactions in anticoagulant therapy: a focus on oncology patients. Expert Rev Clin Pharmacol 2025;18:847-59. DOI: https://doi.org/10.1080/17512433.2025.2585448
17. Kraaijpoel N, Carrier M. How I treat cancer-associated venous thromboembolism. Blood 2019;133:291-8. DOI: https://doi.org/10.1182/blood-2018-08-835595
18. Short NJ, Connors JM. New oral anticoagulants and the cancer patient. Oncologist 2014;19:82-93. DOI: https://doi.org/10.1634/theoncologist.2013-0239
19. Musgrave KM, Power K, Laffan M, et al. Practical treatment guidance for cancer-associated thrombosis - Managing the challenging patient: A consensus statement. Crit Rev Oncol Hematol 2022;171:103599. DOI: https://doi.org/10.1016/j.critrevonc.2022.103599
20. Bellesoeur A, Thomas-Schoemann A, Allard M, et al. Pharmacokinetic variability of anticoagulants in patients with cancer-associated thrombosis: Clinical consequences. Crit Rev Oncol Hematol 2018;129:102-12. DOI: https://doi.org/10.1016/j.critrevonc.2018.06.015
21. Bolek H, Urun Y. Cancer-associated thrombosis and drug-drug interactions of antithrombotic and antineoplastic agents. Cancer 2023;129:3216-29. DOI: https://doi.org/10.1002/cncr.34937
22. Verso M, Munoz A, Bauersachs R, et al. Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism. Eur J Cancer 2021;148:371-81. DOI: https://doi.org/10.1016/j.ejca.2021.02.026
23. Wang TF, Hill M, Mallick R, et al. The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies. Thromb Res 2023;231:128-34. DOI: https://doi.org/10.1016/j.thromres.2023.10.004
24. Anderson WF, Katki HA, Rosenberg PS. Incidence of breast cancer in the United States: current and future trends. J Natl Cancer Inst 2011;103:1397-402. DOI: https://doi.org/10.1093/jnci/djr257
25. Bekaii-Saab TS, Perloff MD, Weemhoff JL, et al. Interactions of tamoxifen, N-desmethyltamoxifen and 4-hydroxytamoxifen with P-glycoprotein and CYP3A. Biopharm Drug Dispos 2004;25:283-9. DOI: https://doi.org/10.1002/bdd.411
26. Wang CL, Wu VC, Tu HT, et al. Risk of major bleeding associated with concomitant use of anticancer drugs and direct oral anticoagulant in patients with cancer and atrial fibrillation. J Thromb Thrombolysis 2022;53633-45.
27. Wang TF, Clarke AE, Awan AA, et al. Hemorrhage risk among patients with breast cancer receiving concurrent direct oral anticoagulants with tamoxifen vs aromatase inhibitors. JAMA Netw Open 2022;5:e2219128. DOI: https://doi.org/10.1001/jamanetworkopen.2022.19128
28. Bosch F, Mulder F, Franken L, et al. Effect of the P-glycoprotein inhibitor tamoxifen on edoxaban plasma levels in women with breast cancer. Thromb Res 2023;228:46-53. DOI: https://doi.org/10.1016/j.thromres.2023.05.021
29. Beavers CJ, Rodgers JE, Bagnola AJ, et al. Cardio-oncology drug interactions: a scientific statement from the American Heart Association. Circulation 2022;145:e811-e38. DOI: https://doi.org/10.1161/CIR.0000000000001056
30. Wang TF, Baumann Kreuziger L, Leader A, et al. Characteristics and outcomes of patients on concurrent direct oral anticoagulants and targeted anticancer therapies-TacDOAC registry: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy. J Thromb Haemost 2021;19:2068-81. DOI: https://doi.org/10.1111/jth.15367
31. Samant TS, Huth F, Umehara K, et al. Ribociclib drug-drug interactions: clinical evaluations and physiologically-based pharmacokinetic modeling to guide drug labeling. Clin Pharmacol Ther 2020;108:575-85. DOI: https://doi.org/10.1002/cpt.1950
32. Liu Z, Du W, Wang Q, et al. In vivo pharmacokinetic interactions of ribociclib with rivaroxaban and apixaban in rats: implications for increased drug exposure and dose adjustments. Front Pharmacol 2025;16:1530806. DOI: https://doi.org/10.3389/fphar.2025.1530806
33. Sahin TK, Kavgaci G, Guven DC, Aksoy S. Drug-drug interactions and special considerations in breast cancer patients treated with CDK4/6 inhibitors: A comprehensive review. Cancer Treat Rev 2025;137:102956. DOI: https://doi.org/10.1016/j.ctrv.2025.102956
34. Leigh J, Qureshi D, Sucha E, et al. A population-based study of factors associated with systemic treatment in advanced prostate cancer decedents. Cancer Med 2023;12:5569-79. DOI: https://doi.org/10.1002/cam4.5401
35. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology, Prostate Cancer, version 2.2020. Plymouth Meeting, National Comprehensive Cancer Networ; 2020.
36. Boujonnier F, Lemaitre F, Scailteux LM. Pharmacokinetic interactions between abiraterone, apalutamide, darolutamide or enzalutamide and antithrombotic drugs: prediction of clinical events and review of pharmacological information. Cardiovasc Drugs Ther 2024;38:757-67. DOI: https://doi.org/10.1007/s10557-023-07453-0
37. Potdar R, Gartrell BA, Given R, et al. Concomitant use of oral anticoagulants in patients with advanced prostate cancer receiving apalutamide: A post-hoc analysis of TITAN and SPARTAN studies. Am J Cancer Res 2022;12:445-50.
38. Wang T-F, Clarke A, Yoo S, et al. Risks of thrombosis and hemorrhage in concurrent use of anticoagulants and potential interacting prostate cancer agents. Cancer 2025;132:e70266. DOI: https://doi.org/10.1002/cncr.70266
39. Lafaie L, Hodin S, Saib S, et al. Tyrosine kinase inhibitors and direct oral anticoagulants: In vitro evaluation of drug-drug interaction mediated by P-glycoprotein. Fundam Clin Pharmacol 2022;36:860-8. DOI: https://doi.org/10.1111/fcp.12769
40. Ng HK, Rogala BG, Ades S, et al. Prospective evaluation of drug-drug interactions in ambulatory cancer patients initiated on prophylactic anticoagulation. J Oncol Pharm Pract 2020;26:1637-42. DOI: https://doi.org/10.1177/1078155220901569
41. Shayeb AM, Urman D, Dizman N, et al. Evaluation of cabozantinib in combination with diret oral anticoagulants or low molecualr weight heparin in renal cell carcinoma. J Clin Oncol 2021;39:291. DOI: https://doi.org/10.1200/JCO.2021.39.6_suppl.291
42. Serrao A, Scalzulli E, Fiori L, et al. Concomitant Administration of direct oral anticoagulants in chronic phase chronic myeloid leukemia patients treated with tyrosine kinase inhibitors. Clin Drug Investig 2020;40:1177-81. DOI: https://doi.org/10.1007/s40261-020-00980-w
CRediT authorship contribution
All authors contributed equally to the composition of this work including review of available literature, drafting the manuscript, and providing critical edits.
How to Cite
1.
Wang T-F, Sanfilippo KM, Carrier M. Pharmacokinetic interactions between anticancer drugs and direct oral anticoagulants: clinical implications for safe anticoagulation. Bleeding Thromb Vasc Biol [Internet]. 2026 Apr. 16 [cited 2026 Oct. 18];5(s1). Available from: https://www.btvb.org/btvb/article/view/434
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