Management of anticoagulation in patients with metastatic castration–resistant prostate cancer receiving abiraterone + prednisone

  • Samuel DubinskyEmail author
  • Alia Thawer
  • Anne G. McLeod
  • Thomas R.J. McFarlane
  • Urban Emmenegger
Review Article



Abiraterone has been proven to be an effective agent used in the management of metastatic castration–resistant prostate cancer, significantly improving overall and progression-free survival. Due to the pharmacodynamic and pharmacokinetic properties of abiraterone, concurrent use with anticoagulation may pose a challenge for clinicians. Thrombosis within the cancer setting continues to increase patient mortality; therefore, appropriate anticoagulation through the use of a management algorithm can reduce adverse events and increase quality of life.


A review of the literature was preformed by a medical oncologist, haematologist and pharmacists to identify relevant randomized controlled trials, meta-analyses and retrospective studies. Major society guidelines were reviewed to further aid in developing the anticoagulation protocol for non-valvular atrial fibrillation and venous thromboembolism within this patient population. After reviewing the literature, a clinical framework was designed to aid clinicians in the management of those patients receiving abiraterone concurrently with an anticoagulant.


In this review, we describe the potential interactions between abiraterone and various anticoagulants and provide management strategies based on the most recent literature for atrial fibrillation, venous thromboembolism and mechanical heart valves to avoid potential drug–drug interactions.


Abiraterone therapy has become a mainstay of the management of advanced prostate cancer and is often used over prolonged years. In this review, we have summarized a framework of how to use abiraterone in men with prostate cancer on anticoagulants. Evidence available to date suggests that patients with an indication for anticoagulation such as atrial fibrillation, venous thromboembolism and mechanical heart valves can be treated safely with abiraterone in the appropriate setting, with appropriate monitoring.


Anticoagulation Abiraterone Pharmacokinetics Supportive care Prostate cancer 



I would like to extend sincere gratitude to Dr. Alia Thawer; she provided extensive support in addition to her expertise that greatly assisted this research. I would also like to show gratitude to Dr. Thomas McFarlane, Dr. Anne McLeod and Dr. Urban Emmenegger for sharing their pearls of wisdom and assistance in critical appraisal during the course of this research.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. Dr. Urban Emmenegger has received clinical research support (personal and institutional) from Janssen Inc., Canada, and has attended advisory board meetings.


The authors of this manuscript have full control of the data presented. We agree to let the Journal of Supportive Care in Cancer review the data if requested.


  1. 1.
    Cooperberg MR, Chan JM (2017) Epidemiology of prostate cancer. World J Urol 35(6):849. CrossRefGoogle Scholar
  2. 2.
    Torre LA, Bray F, Siegal RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. CrossRefGoogle Scholar
  3. 3.
    Stein PD, Hull RD, Kayali F et al (2004) Venous thromboembolism according to age: the impact of an aging population. Arch Intern Med 164(20):2260–2265CrossRefGoogle Scholar
  4. 4.
    Marinigh R, Lip GYH, Fiotti N, Giansanate C, Lane DA (2010) Age as a risk factor for stroke in atrial fibrillation patients: implications for thromboprophylaxis. JACC 56(11).
  5. 5.
    Khorana AA, Connolly GC (2009) Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 27:4839–4847. CrossRefGoogle Scholar
  6. 6.
    Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM (2016) Increasing incidence of metastatic prostate cancer in the United States (2004-2013). Prostate Cancer Prostatic Dis 19:395–397. CrossRefGoogle Scholar
  7. 7.
    Lane DA, Skjoth F, Lip GYH, Larsen TB, Kotecha D (2017) Temporal trends in incidence, prevalence, and mortality of atrial fibrillation in primary care. JAHA 6(5).
  8. 8.
    Easaw JC, Shea-Budgell MA, Wu CMJ et al (2015) Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis. Curr Oncol 22(2):133–143. CrossRefGoogle Scholar
  9. 9.
    Horsted F, West J, Grainge MJ (2012) Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 9:e1001275. CrossRefGoogle Scholar
  10. 10.
    Rehman Y, Rosenberg JE (2012) Abiraterone acetate: oral androgen biosynthesis inhibitor for treatment of castration-resistant prostate cancer. Drug Des Devel Ther 6:13–18. CrossRefGoogle Scholar
  11. 11.
    Agarwal N, Hutson TE, Sonpavde G, Vogelzang (2010) Abiraterone acetate: a promising drug for the treatment of castration-resistant prostate cancer. Future Oncol 6(5):665–679. CrossRefGoogle Scholar
  12. 12.
    Bruno RD, Njar VCO, Vasaitis TS (2011) CYP17 inhibitors for prostate cancer therapy. J Steroid Biochem Mol Biol 125(1–2):23–31. Google Scholar
  13. 13.
    Ryan CJ, Smith MR, de Bono J et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148. CrossRefGoogle Scholar
  14. 14.
    James ND, de Bono JS, Spears MR et al (2017) Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 377:388–351. CrossRefGoogle Scholar
  15. 15.
    Fizazi K, Tran NP, Fein L et al (2017) Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med 377:352–360. CrossRefGoogle Scholar
  16. 16.
    Han CS, Kim IY, Patel R (2015) Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer. Expert Opin Drug Metab Toxicol 11(6):967–975. CrossRefGoogle Scholar
  17. 17.
    Benoist GE, Hendriks RJ, Mulders PFA et al (2016) Pharmacokinetic aspect of the two novel oral drugs used for metastatic castration-resistant prostate cancer: abiraterone acetate and enzalutamide. Clin Pharmacokinet 55(11):1369–1380. CrossRefGoogle Scholar
  18. 18.
    Pia A, Vignani F, Attard G et al (2013) Strategies for managing ACTH dependent mineralocorticoid excess induced by abiraterone. Cancer Treat Rev 39(8):966–973. ReviewCrossRefGoogle Scholar
  19. 19.
    Narum S, Westergren T, Klemp M (2014) Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open 4(5).
  20. 20.
    Lanza FL, Chan FKL, Quigley EMM et al (2009) Prevention of NSAID-related ulcer complications. Am J Gastroenterol 104:728–738. CrossRefGoogle Scholar
  21. 21.
    Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 5:632–634CrossRefGoogle Scholar
  22. 22.
    Macle L, Cairns J, Leblanc L et al (2016) 2016 focused update of the Canadian cardiovascular society guidelines for the management of atrial fibrillation. CJC 32(10):1170–1185. Google Scholar
  23. 23.
    Patel R, Gutierrez A, Rybicki L, Khorana AA (2017) Usefulness of CHADS2 and CHA2DS2-VASc scores for stroke prediction in patients with cancer and atrial fibrillation. Am J Cardiol 120(12):2182–2186CrossRefGoogle Scholar
  24. 24.
    Yeh CH, Gross PL, Weitz JI (2014) Evolving use of new oral anticoagulants for treatment of venous thromboembolism. Blood. 124(7):1020–1028CrossRefGoogle Scholar
  25. 25.
    Dickmann B, Ahlbrecht J, Ay C, Dunkler D, Thaler J, Scheithauer W, Quehenberger P, Zielinski C, Pabinger I (2013) Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study. Haematologica. 98:1309–1314. CrossRefGoogle Scholar
  26. 26.
    Van Hemelrijck MV, Adolfsson J, Garmo H et al (2010) Risk of thromboembolic disease in men with prostate cancer: results from the population-based PCBaSe Sweden. Lancet Oncol 11(5):450–458. CrossRefGoogle Scholar
  27. 27.
    Jamani R, Lee EK, Berry SR et al (2016) High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate. Eur J Clin Pharmacol 72(11):1391–1399CrossRefGoogle Scholar
  28. 28.
    Elyamany G, Alzahrani AM, Bukary E (2014) Cancer-associated thrombosis: an overview. Clin Med Insights Oncol 8:129–137CrossRefGoogle Scholar
  29. 29.
    Kearon C, Akl EA, Comerota AJ et al (2012) Antithrombotic therapy for VTE. CHEST. 141(2):419–494CrossRefGoogle Scholar
  30. 30.
    Eikelboom J, Merli G (2016) Bleeding with direct oral anticoagulants vs. warfarin: clinical experience. Am J Med 129(11):33–40. CrossRefGoogle Scholar
  31. 31.
    Fitzgerald JL, Howes LG (2016) Drug interactions of direct acting oral anticoagulants. Drug Saf 39(9):841–845. CrossRefGoogle Scholar
  32. 32.
    Di Minno A, Frigerio B, Spadarella G. et. al. Old and new oral anticoagulants: food, herbal medicines and drug interactions. Blood Rev 2017; 31(4): 193–203Google Scholar
  33. 33.
    Burnett A, Siegal D, Crowther M (2017) Specific antidotes for bleeding associated with direct oral anticoagulants. BMJ 357:j2216. CrossRefGoogle Scholar
  34. 34.
    Nutescu EA, Burnett A, Fanikos J, Spinler S, Wittkowsky A (2016) Pharmacology of anticoagulants used in the treatment of venous thromboembolism. J Thromb Thrombolysis 41:15–31. CrossRefGoogle Scholar
  35. 35.
    Patel MR, Mahaffey KW, Jyotsna G (2011) Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 365:883–891. CrossRefGoogle Scholar
  36. 36.
    EINSTEIN Investigators (2010) Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 363:2499–2510. CrossRefGoogle Scholar
  37. 37.
    EINSTEIN-PE Investigators (2012) Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 366:1287–1297. CrossRefGoogle Scholar
  38. 38.
    Young A, Marshall A, Thirlwall J et al (2018) 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:JCO2018788034.
  39. 39.
    Bayer INC (2018) Xarelto product monograph. Bayer INC., MississaugaGoogle Scholar
  40. 40.
    Giugliano RP, Ruff CT, Braunwald E et al (2013) Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 269:2093–2104. CrossRefGoogle Scholar
  41. 41.
    Servier Pharmaceuticals (2016) Lixiana product monograph. Servier Canada INC., LavalGoogle Scholar
  42. 42.
    Hokusai-VTE Investigators (2013) Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism. N Engl J Med 369:1406–1415. CrossRefGoogle Scholar
  43. 43.
    Raskob GE, van Es N, Verhamme P et al (2018) Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 378:615–624. CrossRefGoogle Scholar
  44. 44.
    Parasrampuria DA, Truitt KE (2016) Pharmacokinetics and pharmacodynamics of edoxaban, a non-vitamin K antagonist oral anticoagulant that inhibits clotting factor Xa. Clin Pharmacokinet 55:641–655. CrossRefGoogle Scholar
  45. 45.
    Granger CB, Alexander JH, McMurray JJV et al (2011) Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 365:981–992. CrossRefGoogle Scholar
  46. 46.
    Agnelli G, Buller HR, Cohen A et al (2013) Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 369:799–808. CrossRefGoogle Scholar
  47. 47.
    Agnelli G, Buller HR, Cohen A et al (2015) Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost 13:2187–2191CrossRefGoogle Scholar
  48. 48.
    Lyman GH, Bohlke K, Khorana AA et al (2015) Venous thromboembolism prophylaxis and treatment in patients with cancer: American society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 33(6):654–656CrossRefGoogle Scholar
  49. 49.
    Wagman LD, Baird MF, Bennett CL et al (2006) Venous thromboembolic disease: clinical practice guidelines in oncology. J Natl Compr Cancer Netw 4:838–869CrossRefGoogle Scholar
  50. 50.
    Pfizer Pharmaceuticals (2016) Eliquis product monograph. Pfizer Canada INC., KirklandGoogle Scholar
  51. 51.
    Connolly SJ, Ezekowitz MD, Yusuf S et al (2009) Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 361:1139–1151. CrossRefGoogle Scholar
  52. 52.
    Schulman S, Kearon C, Kakkar AK et al (2009) Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 361:2342–2352. CrossRefGoogle Scholar
  53. 53.
    Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL (2013) New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 145(1):105–112. CrossRefGoogle Scholar
  54. 54.
    Abraham NS, Singh S, Alexander GC et al (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:1857. CrossRefGoogle Scholar
  55. 55.
    Boehringer Ingelhem Pharmaceuticals (2016) Pradaxa product monograph. Boehringer Ingelheim Canada Ltd, BurlingtonGoogle Scholar
  56. 56.
    Lee AYY, Levine MN, Baker RI et al (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349:146–153. CrossRefGoogle Scholar
  57. 57.
    Vedovati MC, Germini F, Agnelli G, Becattini C (2015) Direct oral anticoagulants in patients with VTE and cancer. CHEST. 147(2):475–483CrossRefGoogle Scholar
  58. 58.
    Sobieraj DM, Baker WL, Smith E et al (2018) Anticoagulation for the treatment of cancer-associated thrombosis: a systematic review and network meta-analysis of randomized trials. Clin Appl Thromb Hemost 24(9S):182S–187S. CrossRefGoogle Scholar
  59. 59.
    Camm AJ (2001) Atrial fibrillation: is there a role for low-molecular-weight heparin? Clin Cariol 24(3):115–119Google Scholar
  60. 60.
    Sands CD, Chan ES, Welty TE (2002) Revisiting the significance of warfarin protein-binding displacement interactions. Ann Pharmacother 36:1642–1644CrossRefGoogle Scholar
  61. 61.
    Schmidt S, Gonzalez D, Derendorf H (2010) Significance of protein binding in pharmacokinetics and pharmacodynamics. J Pharm Sci 99(3):1107–1112. CrossRefGoogle Scholar
  62. 62.
    Juurlink DN (2007) Drug interactions with warfarin: what clinicians need to know. CMAJ. 177(4):369–371CrossRefGoogle Scholar
  63. 63.
    Holbrook A, Schulman S, Guyatt GH et al (2012) Evidence-based management of anticoagulant therapy. CHEST. 141(2):152–184CrossRefGoogle Scholar
  64. 64.
    Nishimura RA, Otto CM, Bonow RO et al (2017) 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. JACC. 70(2):252–289CrossRefGoogle Scholar
  65. 65.
    Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest physicians evidence-based clinical practice guidelines. CHEST 141(2):576–600.
  66. 66.
    Van de Werf F, Brueckmann M, Connolly SJ et al (2012) A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN). AHJ. 163(6):931–937CrossRefGoogle Scholar
  67. 67.
    Goldberg T, Berrios-Colon E (2013) Abiraterone (Zytiga), a novel agent for the management of castration-resistant prostate cancer. PT. 38(1):23–26Google Scholar
  68. 68.
    Carrier M, Blais N, Crowther M et al (2018) Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus. Curr Oncol 5:329–337Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.University of Waterloo School of PharmacyKitchenerCanada
  2. 2.Odette Cancer CentreSunnybrook Health Sciences CentreTorontoCanada
  3. 3.Department of Medicine, Division of Medical Oncology and HematologySunnybrook Hospital, University of TorontoTorontoCanada

Personalised recommendations