Dabigatran etexilate: A review of its use in the treatment of acute venous thromboembolism and prevention of venous thromboembolism recurrence

Drugs

Volumn 74, Issue 15, 2014, Pages 1785-1800

  Greig, Sarah L ^a   McKeage, Kate ^a  

^a Springer   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

DABIGATRAN; DABIGATRAN ETEXILATE; PLACEBO; WARFARIN; BENZIMIDAZOLES; PYRIDINES;

ACUTE CORONARY SYNDROME; ANTICOAGULATION; ARTHRALGIA; BACKACHE; BLEEDING; BRAIN HEMORRHAGE; COMPARATIVE STUDY; DIARRHEA; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; DYSPNEA; EPIDURAL HEMATOMA; GASTROINTESTINAL HEMORRHAGE; GENITAL BLEEDING; GINGIVA BLEEDING; HEADACHE; HEART INFARCTION; HUMAN; INCIDENCE; LIMB PAIN; LONG TERM CARE; LUNG EMBOLISM; MODERATE RENAL IMPAIRMENT; MUSCLE BLEEDING; NAUSEA; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RECTUM HEMORRHAGE; RECURRENCE RISK; RETROPERITONEAL HEMORRHAGE; REVIEW; RHINOPHARYNGITIS; RISK ASSESSMENT; SPINAL HEMATOMA; TREATMENT DURATION; UNSTABLE ANGINA PECTORIS; VENOUS THROMBOEMBOLISM; ACUTE DISEASE; ADMINISTRATION, ORAL; HUMANS; RECURRENCE;

ACUTE DISEASE; ADMINISTRATION, ORAL; BENZIMIDAZOLES; HUMANS; PYRIDINES; RECURRENCE; VENOUS THROMBOEMBOLISM;

EID: 84910125053     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-014-0304-7     Document Type: Review

References (66)

1. Spyropoulos AC, Turpie AG. Venous thromboembolism management: where do novel anticoagulants fit? Curr Med Res Opin. 2013;29(7):783-90.
2. Beckman MG, Hooper WC, Critchley SE, et al. Venous thromboembolism: a public health concern. Am J Prev Med. 2010;38(4 Suppl):S495-501.
3. Louzada ML, Carrier M, Lazo-Langner A, et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation. 2012;126(4):448-54.
4. Calder KK, Herbert M, Henderson SO. The mortality of untreated pulmonary embolism in emergency department patients. Ann Emerg Med. 2005;45(3):302-10.
5. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e419S-94S.
6. Pollak AW, McBane RD 2nd. Succinct review of the new VTE prevention and management guidelines. Mayo Clin Proc. 2014;89(3):394-408.
7. Abad Rico JI, Llau Pitarch JV, Paramo Fernandez JA. Topical issues in venous thromboembolism. Drugs. 2010;70(Suppl 2):11-8.
8. Boehringer Ingelheim Pharma GmbH & Co. KG. PRADAXA® (dabigatran etexilate mesylate) capsules for oral use: US prescribing information. 2014. http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Accessed 22 Sep 2014.
9. Boehringer Ingelheim Pharma GmbH & Co. KG. Pradaxa 110 mg and 150 mg hard capsules: EU summary of product characteristics. 2014. http://www.ema.europa.eu/docs/en-GB/document-library/EPAR-Product-Information/human/000829/WC500041059.pdf. Accessed 22 Sep 2014.
10. Bauer KA. Pros and cons of new oral anticoagulants. Hematol Am Soc Hematol Educ Program. 2013;2013:464-70.
11. Reilly PA, Lehr T, Haertter S, et al. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63(4):321-8.
12. Burness CB, McKeage K. Dabigatran etexilate: a review of its use for the prevention of venous thromboembolism after total hip or knee replacement surgery. Drugs. 2012;72(7):963-86.
13. Garnock-Jones KP. Dabigatran etexilate: a review of its use in the prevention of stroke and systemic embolism in patients with atrial fibrillation. Am J Cardiovasc Drugs. 2011;11(1):57-72.
14. Sanford M, Plosker GL. Dabigatran etexilate. Drugs. 2008;68(12):1699-709.
15. Eriksson BI, Quinlan DJ, Weitz JI. Comparative pharmacodynamics and pharmacokinetics of oral direct thrombin and factor Xa inhibitors in development. Clin Pharmacokinet. 2009;48(1):1-22.
16. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285-95.
17. Stangier J, Stahle H, Rathgen K, et al. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet. 2008;47(1):47-59.
18. Wienen W, Stassen JM, Priepke H, et al. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost. 2007;98(1):155-62.
19. van Ryn J, Goss A, Hauel N, et al. The discovery of dabigatran etexilate. Front Pharmacol. 2013. doi: 10.3389/fphar.2013.00012.
20. van Ryn J, Grottke O, Spronk H. Measurement of dabigatran in standardly used clinical assays, whole blood viscoelastic coagulation, and thrombin generation assays. Clin Lab Med. 2014;34(3):479-501.
21. Stangier J, Feuring M. Using the HEMOCLOT direct thrombin inhibitor assay to determine plasma concentrations of dabigatran. Blood Coagul Fibrinolysis. 2012;23(2):138-43.
22. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate - a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116-27.
23. Stangier J, Rathgen K, Stahle H, et al. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol. 2007;64(3):292-303.
24. Ring A, Rathgen K, Stangier J, et al. Dabigatran does not prolong the QT interval with supratherapeutic exposure: a thorough QT study in healthy subjects. Clin Drug Investig. 2013;33(5):333-42.
25. Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos. 2008;36(2):386-99.
26. Stangier J, Rathgen K, Stahle H, et al. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49(4):259-68.
27. Stangier J, Stahle H, Rathgen K, et al. Pharmacokinetics and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor, are not affected by moderate hepatic impairment. J Clin Pharmacol. 2008;48(12):1411-9.
28. Hartter S, Sennewald R, Nehmiz G, et al. Oral bioavailability of dabigatran etexilate (Pradaxa®) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 2013;75(4):1053-62.
29. Hartter S, Koenen-Bergmann M, Sharma A, et al. Decrease in the oral bioavailability of dabigatran etexilate after co-medication with rifampicin. Br J Clin Pharmacol. 2012;74(3):490-500.
30. Stangier J, Rathgen K, Stahle H, et al. Coadministration of dabigatran etexilate and atorvastatin: assessment of potential impact on pharmacokinetics and pharmacodynamics. Am J Cardiovasc Drugs. 2009;9(1):59-68.
31. Hartter S, Sennewald R, Schepers C, et al. Pharmacokinetic and pharmacodynamic effects of comedication of clopidogrel and dabigatran etexilate in healthy male volunteers. Eur J Clin Pharmacol. 2013;69(3):327-39.
32. Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-52.
33. Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation. 2014;129(7):764-72.
34. Schulman S, Kearon C, Kakkar AK, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. N Engl J Med. 2013;368(8):709-18.
35. Schulman S, Eriksson H, Goldhaber SZ, et al. Treatment of acute pulmonary embolism with dabigatran or warfarin: a pooled analysis of data from RE-COVER™ and RE-COVER™ II [abstract plus poster]. In: European Society of Cardiology Congress 2014; 30 Aug-3 Sep 2014; Barcelona, Spain.
36. Schulman S, Eriksson H, Goldhaber SZ, et al. Influence of cancer on the efficacy and safety of dabigatran vs warfarin for the acute and extended treatment of venous thromboembolism [abstract no. PO-80]. In: 7th International Conference on Thrombosis and Hemostasis Issues in Cancer; 9-11 May 2014; Bergamo, Italy.
37. Agnelli G, Becattini C. Risk assessment for recurrence and optimal agents for extended treatment of venous thromboembolism. Hematol Am Soc Hematol Educ Program. 2013;2013:471-7.
38. Schulman S, Eriksson H, Goldhaber SZ, et al. Major bleeding events with dabigatran versus warfarin in patients with acute venous thromboembolism: a pooled analysis of RE-COVER and RE-COVER II [abstract no. PC107]. J Thromb Haemost. 2014;12(Suppl. 1):62-3.
39. Burness CB, Perry CM. Rivaroxaban: a review of its use in the treatment of deep vein thrombosis or pulmonary embolism and the prevention of recurrent venous thromboembolism. Drugs. 2014;74(2):243-62.
40. Bristol-Myers Squibb Company. ELIQUIS® (apixaban) tablets for oral use: US prescribing information. 2014. http://packageinserts.bms.com/pi/pi-eliquis.pdf. Accessed 22 Sep 2014.
41. Bloom BJ, Filion KB, Atallah R, et al. Meta-analysis of randomized controlled trials on the risk of bleeding with dabigatran. Am J Cardiol. 2014;113(6):1066-74.
42. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51.
43. Ezekowitz MD, Reilly PA, Nehmiz G, et al. Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007;100(9):1419-26.
44. Majeed A, Hwang HG, Connolly SJ, et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013;128(21):2325-32.
45. Southworth MR, Reichman ME, Unger EF. Dabigatran and postmarketing reports of bleeding. N Engl J Med. 2013;368(14):1272-4.
46. U.S. Food and Drug Administration. FDA drug safety communication: update on the risk for serious bleeding events with the anticoagulant Pradaxa (dabigatran) [media release]. 2 Feb 2012. http://www.fda.gov/Drugs/DrugSafety/ucm326580.htm.
47. European Medicines Agency. European Medicines Agency updates on safety of Pradaxa [media release]. 18 Nov 2011. http://www.ema.europa.eu/docs/en-GB/document-library/Press-release/2011/11/WC500117818.pdf.
48. Harper P, Young L, Merriman E. Bleeding risk with dabigatran in the frail elderly. N Engl J Med. 2012;366(9):864-6.
49. Pfeilschifter W, Luger S, Brunkhorst R, et al. The gap between trial data and clinical practice - an analysis of case reports on bleeding complications occurring under dabigatran and rivaroxaban anticoagulation. Cerebrovasc Dis. 2013;36(2):115-9.
50. U.S. Food and Drug Administration. FDA drug safety communication: FDA study of Medicare patients finds risks lower for stroke and death but higher for gastrointestinal bleeding with Pradaxa (dabigatran) compared to warfarin [media release]. 13 May 2014. http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm397179.htm.
51. Cohen D. Dabigatran: how the drug company withheld important analyses. BMJ. 2014. doi: 10.1136/bmj.g4670.
52. Boehringer Ingelheim Pharma GmbH & Co. KG. Benefits and safety of Pradaxa® (dabigatran etexilate mesylate) repeatedly confirmed [media release]. 23 Jul 2014. http://us.boehringer-ingelheim.com/news-events/press-releases/press-release-archive/2014/07-23-14-benefits-safety-pradaxa-dabigatran-etexilate-mesylate-repeatedly-confirmed.html.
53. Clemens A, Fraessdorf M, Friedman J. Cardiovascular outcomes during treatment with dabigatran: comprehensive analysis of individual subject data by treatment. Vasc Health Risk Manag. 2013;9:599-615.
54. Artang R, Rome E, Nielsen JD, et al. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors. Am J Cardiol. 2013;112(12):1973-9.
55. Hoffman A, Galle PR. Gastrointestinal disorders and dabigatran. Scand J Gastroenterol. 2013;48(1):9-16.
56. Schulman S. Treatment of venous thromboembolism with dabigatran. Curr Opin Pulm Med. 2012;18(5):410-5.
57. Nieuwlaat R, Healey JS, Ezekowitz M, et al. Management of dyspepsia symptoms on dabigatran during RELY-ABLE: long-term follow-up study after RE-LY [abstract no. P549]. In: 35th Congress of the European Society of Cardiology; 31 Aug-4 Sep 2013; Amsterdam, The Netherlands.
58. Kang N, Sobieraj DM. Indirect treatment comparison of new oral anticoagulants for the treatment of acute venous thromboembolism. Thromb Res. 2014;133(6):1145-51.
59. Mantha S, Ansell J. Indirect comparison of dabigatran, rivaroxaban, apixaban and edoxaban for the treatment of acute venous thromboembolism. J Thromb Thrombolysis. 2014. doi: 10.1007/s11239-014-1102-5.
60. Steiner T, Bohm M, Dichgans M, et al. Recommendations for the emergency management of complications associated with the new direct oral anticoagulants (DOACs), apixaban, dabigatran and rivaroxaban. Clin Res Cardiol. 2013;102(6):399-412.
61. Kaatz S, Kouides PA, Garcia DA, et al. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol. 2012;87(Suppl 1):S141-5.
62. Levine M, Goldstein JN. Emergency reversal of anticoagulation: novel agents. Curr Neurol Neurosci Rep. 2014;14(8). doi: 10.1007/s11910-014-0471-7 (article no. 417).
63. Boehringer Ingelheim Pharma GmbH & Co. KG. Boehringer Ingelheim's investigational antidote for Pradaxa® (dabigatran etexilate mesylate) receives FDA Breakthrough Therapy Designation [media release]. 26 Jun 2014. http://us.boehringer-ingelheim.com/news-events/press-releases/press-release-archive/2014/06-26-14-boehringer-ingelheim-investigational-antidote-pradaxa-dabigatran-etexilate-mesylate-fda-breakthrough-therapy-designation.html.
64. Glund S, Stangier J, Schmohl M, et al. A specific antidote for dabigatran: immediate, complete and sustained reversal of dabigatran induced anticoagulation in healthy male volunteers [abstract no. 17765]. In: American Heart Association Scientific Sessions; 16-20 Nov 2013; Dallas.
65. Boehringer Ingelheim. A phase III case series clinical study of the reversal of the anticoagulant effects of dabigatran by intravenous administration of 5.0 g idarucizumab (BI 655075) in patients treated with dabigatran etexilate who have uncontrolled bleeding or require emergency surgery or procedures. RE-VERSE AD (a study of the RE-VERSal Effects of idarucizumab on Active Dabigatran) trial [ClinicalTrials.gov identifier NCT02104947]. US National Insitutes of Health, ClinicalTrials.gov. 2014. http://www.clinicaltrials.gov/. Accessed 22 Sep 2014.
66. Wolowacz S, Brockbank J, Sunderland TJ, et al. Cost-effectiveness of dabigatran etexilate for the secondary prevention of recurrent deep vein thrombosis and pulmonary embolism in the United Kingdom [abstract no. PVC81]. Value Health. 2013;16(7):A526.