Fondapatinux: A new synthetic and selective inhibitor of Factor Xa

Best Practice and Research: Clinical Haematology

Volumn 17, Issue 1, 2004, Pages 89-104

  Bauer, Kenneth A ^a,b  

^a HARVARD MEDICAL SCHOOL   (United States)

^b BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Acute coronary syndromes; Fondaparinux; Heparin; Pentassaccharide; Pharmacokinetics; Surgery; Thromboprophylaxis; Venous thromboembolism

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBIN III; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; DALTEPARIN; DIGOXIN; ENOXAPARIN; FONDAPARINUX; HEMOGLOBIN; HEPARIN; LOW MOLECULAR WEIGHT HEPARIN; NONSTEROID ANTIINFLAMMATORY AGENT; PIROXICAM; PLACEBO; THROMBIN; WARFARIN; POLYSACCHARIDE;

ACUTE DISEASE; BLEEDING DISORDER; CLINICAL TRIAL; DEEP VEIN THROMBOSIS; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG FATALITY; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SELECTIVITY; HEART INFARCTION; HEART MUSCLE ISCHEMIA; HIP FRACTURE; HUMAN; LUNG EMBOLISM; NONHUMAN; ORTHOPEDIC SURGERY; PHARMACODYNAMICS; POPULATION RESEARCH; POSTOPERATIVE CARE; POSTOPERATIVE THROMBOSIS; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SURGICAL RISK; SYMPTOMATOLOGY; THROMBOCYTOPENIA; THROMBOSIS PREVENTION; TOTAL HIP PROSTHESIS; TOTAL KNEE REPLACEMENT; UNSTABLE ANGINA PECTORIS; VENOUS THROMBOEMBOLISM; DRUG ANTAGONISM; POSTOPERATIVE COMPLICATION; TREATMENT OUTCOME; VEIN THROMBOSIS;

FACTOR XA; HUMANS; MYOCARDIAL ISCHEMIA; ORTHOPEDIC PROCEDURES; POLYSACCHARIDES; POSTOPERATIVE COMPLICATIONS; TREATMENT OUTCOME; VENOUS THROMBOSIS;

EID: 2942733232     PISSN: 15216926     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.beha.2004.03.004     Document Type: Review

References (51)

1. van Boeckel CAA & Petitou M. The unique antithrombin III binding domain of heparin: a lead to new synthetic antithrombotics. Angewandte Chemie 1993; 32: 1671-1690. (international edition in English).
2. Petitou M, Lormeau JC & Choay J. Chemical synthesis of glycosaminoglycans: new approaches to antithrombotic drugs. Nature 1991; 350(supplement): 30-33.
3. Petitou M, Hérault JP, Bernat A, et al. Synthesis of thrombin-inhibiting heparin mimetics without side effects. Nature 1999; 398: 417-422.
4. Herbert JM, Petitou M, Lormeau JC, et al. SR 90107/Org 3 1540, a novel anti-factor Xa antithrombotic agent. Cardiovascular Drug Review 1997; 15: 1-26.
5. Turpie AGG, Gallus AS & Hoek JA. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. The New England Journal of Medicine 2001; 344: 619-625.
6. Bauer KA, Eriksson BI, Lassen MR & Turpie AGG. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. The New England Journal of Medicine 2001; 345: 1305-1310.
7. Eriksson BI, Bauer KA, Lassen MR & Turpie AGG. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. The New England Journal of Medicine 2001; 345: 1298-1304.
8. Lassen MR, Bauer KA, Eriksson BI & Turpie AGG. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet 2002; 359: 1715-1720.
9. Turpie AGG, Bauer KA, Eriksson BI & Lassen MR. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet 2002; 359: 1721-1726.
10. Turpie AGG, Bauer KA, Eriksson BI & Lassen MR. Fondaparinux versus enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery. A meta-analysis of 4 randomized studies. Archives of Internal Medicine 2002; 162: 1833-1840.
11. Eriksson BI & Lassen MR. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery. A multicenter, randomized, placebo-controlled, double-blind study. Archives of Internal Medicine 2003; 163: 1337-1342.
12. Agnelli G, Bergqvist D, Cohen A, et al. A randomized double-blind study to compare the efficacy and safety of fondaparinux with dalteparin in the prevention of venous thromboembolism after high-risk abdominal surgery: the PEGASUS study. Journal of Thrombosis and Haemostasis 2003; 1(supplement 1). Abstract OC006.
13. Cohen AT, Gallus AS, Lassen MR, et al. Fondaparinux versus placebo for the prevention of venous thromboembolism in acutely ill medical patients (ARTEMIS). Journal of Thrombosis and Haemostasis 2003; 1(supplement 1). Abstract P1915.
14. The Rembrandt Investigators, Treatment of proximal deep vein thrombosis with a novel synthetic compound (SR90107A/ORG31540) with pure anti-factor Xa activity. A phase II evaluation. Circulation 2000; 102: 2726-2731.
15. The Matisse Investigators, The MATISSE-DVT trial, a randomized, double-blind study comparing once-daily fondaparinux (Arixtrag) with the low-molecular-weight heparin enoxaparin, twice daily, in the initial treatment of symptomatic deep vein thrombosis. Journal of Thrombosis and Haemostasis 2003; 1(supplement 1). Abstract OC332.
16. The Matisse Investigators, Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism. The New England Journal of Medicine 2003; 349: 1695-1702.
17. Coussement PK, Bassand JP, Convens C, et al. A synthetic factor Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. European Heart Journal 2001; 22: 1716-1724.
18. Vuillemenot A, Schiele F, Meneveau N, et al. Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent. A pilot study in the setting of coronary angioplasty. Thrombosis and Haemostasis 1999; 81: 214-220.
19. Simoons M. Oral presentation on the PENTUA clinical trial. 74th Annual Scientific Sessions of the American Heart Association, Anaheim CA, USA, 14 November 2001.
20. Petitou M, Duchaussoy P, Lederman 1, et al. Synthesis of heparin fragments: a alpha-methyl pentaoside with high affinity for antithrombin III. Carbohydrate Research 1987; 167: 67-75.
21. Paolucci F, Clavies M, Donat F, et al. Fondaparinux sodium mechanism of action: identification of specific binding to purified and human plasma-derived proteins. Clinical Pharmccokinetics 2002; 41(supplement): 11-18.
22. Olson ST, Björk I, Sheffer R, et al. Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions. Resolution of the antithrombin conformational change contribution to heparin rate enhancement. Journal of Biological Chemistry 1992; 267: 12528-12538.
23. Hérault JP, Bernat A, Pflieger AM, et al. Comparative effect of two direct and indirect inhibitors on free and clot-bound prothrombinase. The Journal of Pharmacology and Experimental Therapeutics 1997; 283: 16-22.
24. Lormeau JC & Hérault JP. The effect of the synthetic pentasaccharide SR90107/ORG31540 on thrombin generation ex vivo is uniquely due to AT-mediated neutralization of factor Xa. Thrombosis and Haemostosis 1995; 74: 1474-1477.
25. Walenga JM, Jeske WP, Bara L, et al. Biochemical and pharmacologic rationale for the development of a synthetic pentasaccharide. Thrombosis Research 1997; 86: 1-36.
26. Boneu B, Necciari J, Cariou R, et al. Pharmacokinetics and tolerance of the natural pentasaccharide (SR90107/ORG31540) with high affinity to antithrombin III in man. Thrombosis and Haemostasis 1995; 74: 1468-1473.
27. Paolucci F, van Aarle FGB, Capdevila A, et al. Two sensitive chromogenic assays of fondaparinux sodium (Arixtra®), a new synthetic and selective inhibitor of factor Xa, in plasma. Clinical Laboratory 2003; 49: 451-460.
28. Béguin S, Choay J & Hemker HC. The action of a synthetic pentasaccharide on thrombin generation in whole plasma. Thrombosis and Haemostasis 1989; 61: 397-401.
29. Lormeau JC & Hérault JP. Comparative inhibition of extrinsic and intrinsic thrombin generation by standard heparin, a low molecular weight heparin and the synthetic AT-III-binding pentasaccharide. Thrombosis and Haemostasis 1993; 69: 152- 156.
30. Elalamy I, Lecrubier C, Potevin F, et al. Absence of in vitro cross-reaction of pentasaccharide with the plasma heparin dependent factor of twenty-five patients with heparin associated thrombocytopenia. Thrombosis and Haemostasis 1995; 74: 1384-1385.
31. Ahmad S, Jeske WP, Walenga JM, et al. Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies. Clinical and Applied Thrombosis/Hemostasis 1999; 5: 259-266.
32. Amiral J, Lormeau JC, Marfaing-Koka A, et al. Absence of cross-reactivity of SR90107A/ORG31540 pentasaccharide with antibodies to heparin-PF4 complexes developed in heparin-induced thrombocytopenia. Blood Coagulation and Fibrinolysis 1997; 8: 114-117.
33. Walenga JM, Bara L, Petitou M, et al. The inhibition of the generation of thrombin and the antithrombotic effect of a pentasaccharide with sole anti-factor Xa activity. Thrombosis Research 1988; 51: 23-33.
34. Walenga JM, Hoppensteadt D, Mayuga M, et al. Functionality of pentasaccharide depends on endogenous antithrombin levels. Blood 2000; 96: 817a.
35. Bijsterveld NR, Moons AH, Boekholdt M, et al. Ability of recombinant activated factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation 2002; 106: 2550-2554.
36. Donat F, Duret JP, Santoni A, et al. The pharmacokinetics of fondaparinux sodium in healthy volunteers. Clinical Pharmacokinetics 2002; 41: 1-9.
37. Lieu C, Shij, Donat F, et al. Fondaparinux sodium is not metabolised in mammalian liver fractions and does not inhibit cytochrome P450-mediated metabolism of concomitant drugs. Clinical Pharmacokinetics 2002; 41(supplement): 19-26.
38. Faaij RA, Burggraaf J, Schoemaker HC, et al. The influence of renal function on the pharmacokinetics and pharmacodynamics of ORG31540/SR90107A. Thrombosis and Haemostasis 1997; 77(supplement): 379.
39. Lagrange F, Vergnes C, Brun JL, et al. Absence of placental transfer of pentasaccharide (fondaparinux Arixtra®) in the dually perfused cotyledon in vitro. Thrombosis and Haemostasis 2002; 87: 831-835.
40. Faaij RA, Burggraaf J, Schoemaker RC, et al. The synthetic pentasaccharide fondaparinux sodium does not interact with oral warfarin. Clinical Pharmacokinetics 2002; 41(supplement): 27-29.
41. Ollier C, Santoni A, Faaij RA, et al. Absence of interaction of fondaparinux sodium with aspirin and piroxicam in healthy male volunteers. Clinical Pharmacokinetics 2002; 41(supplement): 31-37.
42. Mant T, Fournié P, Ollier C, et al. Absence of interaction of fondaparinux sodium with digoxin in healthy volunteers. Clinical Pharmacokinetics 2002; 41(supplement): 39-45.
43. Geerts; WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Sixth ACCP Consensus Conference on Antithrombotic Therapy. Chest 2001; 119(supplement): 132S-175S.
44. Committee for Proprietary Medicinal Products. Points to consider on clinical investigation of medicinal products for prophylaxis of intra- and postoperative venous thromboembolic risk. London: The European Agency for the Evaluation of Medicinal Products, 29 June 2000, CPMP/EWP/707/98.
45. Bauer KA, Eriksson BI, Lassen MR, Turpie AGG., Consistency of fondaparinux superiority over enoxaparin in prevention of venous thromboembolism in orthopaedic surgery according to different composite efficacy endpoints. Seventh Annual Meeting of the European Haematology Association. Bologna, Italy: Monduzzi Editore, 2002, pp. 289-292.
46. Turpie AGG, Bauer KA, Eriksson BI & Lassen MR. Effect on efficacy and safety of the timing of the first pentasaccharide (fondaparinux Arixtra®) administration in the prevention of venous thromboembolism (VTE) after major orthopedic surgery. Thrombosis and Haemostasis 2003; 90: 364-358.
47. Eikelboom JW, Quinlan DJ & Douketis JD. Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomized trials. Lancet 2001; 3S8: 9-15.
48. Eriksson BI & Lassen MR. Persistence of the risk of venous thromboembolism for at least four weeks after hip fracture surgery: evidence from the fondaparinux hip fracture surgery database. Journal of Thrombosis and Haemostasis 2003; 1(supplement 1): P2080.
49. Lassen MR & Eriksson Bl. Efficacy of fondaparinux (Arixtra®) in extended thromboprophylaxis in hip fracture surgery is irrespective of patient and surgical characteristics: subgroup analyses of the PENTHIFRA-PLUS study. Journal of Thrombosis and Haemostasis 2003; 1(supplement 1): P2062.
50. Bauer KA, Eriksson BI, Lassen MR & Turpie AGG. No episode of thrombocytopenia after four-week administration of fondaparinux, a new synthetic and selective inhibitor of factor Xa, in the PENTHIFRA-PLUS study. Journal of Thrombosis and Haemostasis 2003; 1(supplement 1): P2050.
51. Lassen MR & Eriksson BI. Absence of transaminase increase after four-week administration of fondaparinux (Arixtra®), a new synthetic and selective inhibitor of factor Xa, in the PENTHIFRA-PLUS study. Journal of Thrombosis and Haemostasis 2003; 1(supplement 1): P2052.