Tinzaparin sodium: A review of its pharmacology and clinical use in the prophylaxis and treatment of thromboembolic disease

Drugs

Volumn 64, Issue 13, 2004, Pages 1479-1502

  Cheer, Susan M ^a   Dunn, Christopher J ^a   Foster, Rachel ^a  

^a ADIS INTERNATIONAL LIMITED   (New Zealand)

Author keywords

Deep vein thrombosis; Pharmacodynamics; Pharmacokinetics; Pulmonary embolism; Therapeutic use; Tinzaparin sodium; Venous thromboembolism

Indexed keywords

DALTEPARIN; DEXTRAN; ENOXAPARIN; HEPARIN; LOW MOLECULAR WEIGHT HEPARIN; TINZAPARIN; WARFARIN;

ANTICOAGULATION; BLEEDING; BLOOD CLOTTING; BODY MASS; BODY WEIGHT; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; COST BENEFIT ANALYSIS; COST EFFECTIVENESS ANALYSIS; DEEP VEIN THROMBOSIS; DOSE CALCULATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG ELIMINATION; DRUG SAFETY; DRUG TOLERABILITY; DRUG TOLERANCE; DRUG USE; HEMATOMA; HEMODIALYSIS; HOME CARE; HOSPITAL COST; HUMAN; KIDNEY DISEASE; KNEE ARTHROPLASTY; LIPID BLOOD LEVEL; LIPID METABOLISM; LUNG EMBOLISM; META ANALYSIS; ORTHOPEDIC SURGERY; OUTPATIENT; PREGNANCY; REVIEW; SIDE EFFECT; THROMBOCYTOPENIA; THROMBOEMBOLISM; TREATMENT OUTCOME;

AGE FACTORS; CLINICAL TRIALS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; FIBRINOLYTIC AGENTS; HEPARIN, LOW-MOLECULAR-WEIGHT; HUMANS; PREGNANCY; THROMBOEMBOLISM; TREATMENT OUTCOME;

SUIDAE;

EID: 3242790119     PISSN: 00126667     EISSN: None     Source Type: Journal    
DOI: 10.2165/00003495-200464130-00006     Document Type: Review

References (101)

1. White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107: 14-8
2. Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest 2001 Jan; 119 (1 Suppl.): 132-175S
3. Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992 Jan 1; 79: 1-17
4. Morris TA. Heparin and low molecular weight heparin: background and pharmacology. Clin Chest Med 2003; 24: 39-47
5. Pineo GF, Hull RD. Low-molecular-weight heparin: prophylax-is and treatment of venous thromboembolism. Ann Rev Med 1997; 48: 79-91
6. Hull RD, Pineo GF, Valentine KA. Treatment and prevention of venous thromboembolism. Sem Thromb Hemost 1998; 24 (5 Suppl. 1): 21-31
7. Hirsh J, Warkentin TE, Raschke R, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. Chest 1998 Nov; 114: 489-510
8. Boneu B. Low molecular weight heparins: are they superior to unfractionated heparins to prevent and to treat deep vein thrombosis? Thromb Res 2000; 100: 113-20
9. Neely JL, Carlson SS, Lenhart SE. Tinzaparin sodium: a low-molecular-weight heparin. Am J Health Syst Pharm 2002 Aug 1; 59 (15): 1426-36
10. Friedel HA, Balfour JA. Tinzaparin: a review of its pharmacology and clinical potential in the prevention and treatment of thromboembolic disorders. Drugs 1994; 48: 638-60
11. Barrowcliffe TW, Curtis AD, Johnson EA, et al. An international standard for low molecular weight heparin. Thromb Haemost 1988; 60 (1): 1-7
12. Tinzaparin sodium. European Parmacopoeia 2002; 4/e: 2040-1
13. Matzsch T, Bergqvist D, Hedner U, et al. Effects of an enzymatically depolymerized heparin as compared with conventional heparin in healthy volunteers. Thromb Haemost 1987; 57 (1): 97-101
14. Matzsch T, Bergqvist D, Fredin H, et al. Influence of a low molecular weight heparin on the inhibition of factor Xa and thrombin in hip surgery. Thromb Res 1989; 56 (4): 559-64
15. Fossler MJ, Barrett JS, Hainer JW, et al. Pharmacodynamics of intravenous and subcutaneous tinzaparin and heparin in healthy volunteers. Am J Health Syst Pharm 2001 Sep 1; 58 (17): 1614-21
16. Hainer JW, Barrett JS, Assaid CA, et al. Dosing in heavyweight/obese patients with the LMWH, tinzaparin: a pharmacodynamic study. Thromb Haemost 2002 May; 87 (5): 817-23
17. Bara L, Planes A, Samama MM. Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-IIa activities, and D-dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery. Br J Haematol 1999; 104: 230-40
18. Leizorovicz A, Bara L, Samama MM, et al. Factor Xa inhibition: correlation between the plasma levels of anti-Xa activity and occurrence of thrombosis and haemorrhage. Haemostasis 1993 Mar; 23 Suppl. 1: 89-98
19. Planès A, Samama MM, Lensing AWA, et al. Prevention of deep vein thrombosis after hip replacement: comparison between two low-molecular-weight heparins, tinzaparin and enoxaparin. Thromb Haemost 1999; 81: 22-5
20. Weite JI. Low-molecular-weight heparin. N Engl J Med 1997 Sep 4; 337 (10): 688-98
21. Holst J, Lindblad B, Bergqvist D, et al. Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, logiparin): an experimental investigation in healthy volunteers. Blood Coagul Fibrinolysis 1994; 5 (5): 795-803
22. Crowther MA, Berry LR, Monague PT, et al. Mechanism responsible for the failure of protamine to inactivate low-molecular-weight heparin. Br J Haematol 2002; 116 (1): 178-86
23. Mousa SA, Bozarth J, Barrett JS. Pharmacodynamic properties of the low molecular weight heparin, tinzaparin: effect of molecular weight distribution on plasma tissue factor pathway inhibitor in healthy human subjects. J Clin Pharmacol 2003 Jul; 43 (7): 727-34
24. Gouin-Thibault I, Pautas E, Depasse F, et al. Heparin-releasable TFPI is not depleted after repeated injections of tinzaparin at therapeutic dosages for up to 30 days. J Thromb Haemost 2003; 1: 2694-5
25. Depasse F, Gonzalez de Suso MJ, Lagoutte I, et al. Comparative study of the pharmacokinetic profiles of two LMWHs-bemiparin (3500 IU, anti-Xa) and tinzaparin (4500 IU, anti-Xa)-administered subcutaneously to healthy male volunteers. Thromb Res 2003 Jan 25; 109 (2-3): 109-17
26. Valentin S, Ostergaard P, Kristensen H, et al. Synergism between full length TFPI and heparin: evidence for TFPI as an important factor for the antithrombotic activity of heparin. Blood Coagul Fibrinolysis 1992 Apr; 3: 221-2
27. Kristensen HI, Ostergaard PB, Nordfang O, et al. Effect of tissue factor pathway inhibitor (TFPI) in the HEFTEST assay and in an amidolytic anti factor Xa assay for LMW heparin. Thromb Haemost 1992; 68 (3): 310-4
28. Amirkhosravi A, Mousa SA, Amaya M, et al. Antimetastatic effect of tinzaparin, a low-molecular weight heparin. J Thromb Haemost 2003; 1: 1972-6
29. Sobel M, Adelman B. Characterization of platelet binding of heparins and other glycosaminoglycans. Thromb Res 1988; 50 (6): 815-26
30. Padilla A, Gray E, Pepper DS, et al. Inhibition of thrombin generation by heparin and low molecular weight (LMW) heparins in the absence and presence of platelet factor 4 (PF4). Br J Haematol 1992 Oct; 82: 406-13
31. Fareed J, Walenga JM, Hoppensteadt D, et al. Biochemical and pharmacologie inequivalence of low molecular weight hepa-rins. Ann N Y Acad Sci 1989; 556:333-53
32. Mousa SA, Forsythe M, Walenga J, et al. Synergy between low molecular weight heparin, tinzaparin and platelet GPIIb/IIIa antagonists, ReoPro and roxifiban in improving antiplatelet and anticoagulant efficacy. XVIIth Congress of the International Society on Thrombosis and Haemostasis; 1999 Aug 14; Washington, DC
33. Olivecrona T, Bengtsson-Olivecrona G, Ostergaard P, et al. New aspects on heparin and lipoprotein metabolism. Haemostasis 1993 Mar; 23 Suppl. 1: 150-60
34. Liu G, Bengtsson-Olivecrona G, Ostergaard P, et al. Low-M(r) heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clear-ance of the enzyme. Biochem J 1991; 273 (3): 747-52
35. Akiba T, Tachibana K, Ozawa K, et al. Long-term use of low molecular weight heparin ameliorates hyperlipidemia in pa-tients in hemodialysis. ASAIO J 1992; 38 (3): M326-30
36. Barrett JS, Gibiansky E, Hull RD, et al. Population pharmaco-dynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis. Int J Clin Pharmacol Ther 2001 Oct; 39 (10): 431-46
37. Pedersen PC, Ostergaard PB, Hedner U, et al. Pharmacokinetics of a low molecular weight heparin, logiparin, after intravenous and subcutaneous administration to healthy volunteers. Thromb Res 1991; 61 (5-6): 477-87
38. Wolf H. Low-molecular-weight heparin. Med Clin North Am 1994 May; 78: 733-43
39. Young E, Wells P, Holloway S, et al. Ex-vivo and in-vitro evidence that low molecular weight heparins exhibit less bind-ing to plasma proteins than unfractionated heparin. Thromb Haemost 1994; 71(3): 300-4
40. Brindley CJ, Taylor T, Diness V, et al. Relationship between pharmacokinetics and pharmacodynamics of tinzaparin (logiparin), a low molecular weight heparin, in dogs. Xenobiotica 1993 Jun; 23: 575-88
41. Bouchelouche PN, Ostergaard PB, Mortensen SA, et al. Comparative pharmacokinetics of a low molecular weight heparin (LHN-1, Novo), and conventional heparin after intravenous injection. Thromb Res 1986; Suppl. 6: 89
42. Pharmion Corporation. Innohep® (tinzaparin sodium injection). Boulder (CO): Pharmion Corporation, 2003
43. Hainer JW, Sherrard DJ, Swan SK, et al. Intravenous and subcutaneous weight-based dosing of the low molecular weight heparin tinzaparin (Innohep) in end-stage renal disease patients undergoing chronic hemodialysis. Am J Kidney Dis 2002 Sep; 40 (3): 531-8
44. Siguret V, Pautas E, Fevrier M, et al. Elderly patients treated with tinzaparin (Innohep) administered once daily (175 antiXa 1U/kg): anti-Xa and anti-IIa activities over 10 days. Thromb Haemost 2000 Nov; 84 (5): 800-4
45. Nagge J, Crowther M, Hirsh J. Is impaired renal function a contraindication to the use of low-molecular-weight heparin? Arch Intern Med 2002; 162: 2605-9
46. Smith MP, Norris LA, Steer PJ, et al. Tinzaparin sodium for thrombosis treatment and prevention during pregnancy. Am J Ostet Gynecol 2004; 190 (2): 495-501
47. Lassen MR, Borris LC, Jensen HP, et al. Dose relation in the prevention of proximal vein thrombosis with a low molecular weight heparin (tinzaparin) in elective hip arthroplasty. Clin Appl Thromb Hemost 2000 Jan; 6 (1): 53-7
48. Lassen MR, Borris LC, Christiansen HM, et al. Prevention of thromboembolism in 190 hip arthroplasties: comparison of LMW heparin and placebo. Acta Orthop Scand 1991 Feb; 62: 33-8
49. Mätzsch T, Berqvist D, Fredin H, et al. Comparison of the throboprophylactic effect of a low molecular weight heparin versus dextran in total hip replacement. Thromb Haemorrhagic Disord 1991; 3: 25-9
50. Leizorovicz A, Picolet H, Peyrieux JC, et al. Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of Logiparin and standard heparin. Br J Surg 1991; 78 (4): 412-6
51. Lausen I, Jensen R, Jorgensen LN, et al. Incidence and preven-tion of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis. Eur J Surg 1998; 164 (9): 657-63
52. Bergqvist D, Flordal PA, Friberg B, et al. Thromboprophylaxis with a low molecular weight heparin (tinzaparin) in emergency abdominal surgery: a double-blind multicenter trial. Vasa 1996; 25 (2): 156-60
53. Hull R, Raskob G, Pineo G, et al. A comparison of subcutane-ous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation. N Engl J Med 1993 Nov 4; 329: 1370-6
54. Mätzsch T, Berqvist D, Fredin H, et al. Low molecular weight heparin compared with dextran as prophylaxis against thrombosis after total hip replacement. Acta Chirurg Scand 1990; 156: 445-50
55. Jørgensen LN, Lausen I, Morten S, et al. Prolonged thromboprophylaxis with low molecular weight heparin (tinzaparin) following major general surgery: an individual patient data meta-analysis [abstract no. 1952]. Blood 2002; 100 (11 Pt 1): 501a
56. Green D, Lee MY, Lim AC, et al. Prevention of thromboembolism after spinal cord injury using low-molecular-weight heparin. Ann Intern Med 1990 Oct 15; 113: 571-4
57. Green D, Chen D, Chmiel JS, et al. Prevention of thromboembolism in spinal cord injury: role of low molecular weight heparin. Arch Phys Med Rahabil 1994; 75: 290-2
58. Jorgensen PS, Warming T, Hansen K, et al. Low molecular weight heparin (Innohep) as thromboprophylaxis in outpatients with a plaster cast: a venografic controlled study. Thromb Res 2002 Mar 15; 105 (6): 477-80
59. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin compared with continuous intrave-nous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992 Apr 9; 326: 975-82
60. Pineo GF, Hull RD, Raskob GE, et al. Decreased mortality in cancer patients treated for proximal deep vein thrombosis with low-molecular-weight heparin as compared with unfractionated heparin [abstract no. OC-1566]. Thromb Haemost 1997 Jun 6; Suppl.: 384
61. Hull R, Pineo GF, Mah AF, et al. A randomized trial evaluating long-term low-molecular-weight heparin therapy for three months vs. intravenous heparin followed by warfarin sodium in patients with current cancer [abstract]. J Thromb Haemostasis 2003; 1 Suppl. 1: P1373a
62. Hull RD, Raskob GE, Brant RF, et al. Low-molecular-weight heparin vs heparin in the treatment of patients with pulmonary embolism. Arch Intern Med 2000 Jan 24; 160: 229-36
63. Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997; 337: 663-9
64. Kovacs MJ, Wells PS, Rodger M, et al. A randomised trial comparing two low molecular weight heparins for the outpatient treatment of DVT or PE [abstract no. 1116]. Blood 2001 Nov 16; 98 (Pt 1): 265-6
65. Hull RD, Pineo GF, Mah AF, et al. Home-life: safety and efficacy results for a study investigating the long-term out-of-hospital treatment of patients with proximal venous thrombosis using subcutaneous low-molecular-weigh heparin versus warfarin [abstract no. OC1647]. 18th Congress of the International Society on Thrombosis and Haemostasis; 2001 Jul 6-12; Paris
66. Pineo GF, Hull RD, Mah AF, et al. Does rebounding exist? A comparison of venous thromboembolic event rates in the post-treatment period for patients randomised to long-term low-molecular-weight heparin vs warfarin sodium [abstract no. P1882], J Thromb Haemost 2003; 1 Suppl.: 384
67. Hull RD, Pineo GF, Raskob GE. The economic impact of treating deep vein thrombosis with low-molecular-weight heparin: outcome of therapy and health economy aspects: low-molecular-weight heparin versus unfractionated heparin. Haemostasis 1998 Nov; 28: 8-16
68. Rose P, Bell D, Green ES, et al. The outcome of ambulatory DVT management using a multidisciplinary approach. Clin Lab Haematol 2001 Oct; 23 (5): 301-6
69. Lapidus L, Borretzen J, Fahlen M, et al. Home treatment of deep vein thrombosis. An out-patient treatment model with once-daily injection of low-molecular-weight heparin (tinzaparin) in 555 patients. Pathophysiol Haemost Thromb 2002 Mar; 32 (2): 59-66
70. Lim AY, Par DG, Stableforth DE, et al. Early discharge and home supervision of patients with pulmonary embolism treated with low molecular weight heparin. Eur J Intern Med 2003; 14 (2): 89-93
71. Harrison L, McGinnis J, Crowther M, et al. Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin. Arch Intern Med 1998; 158 (18): 2001-3
72. Simpson HKL, Baird J, Allison M, et al. Long-term use of the low molecular weight heparin tinzaparin in haemodialysis. Haemostasis 1996; 26: 90-7
73. Egfjord M, Rosenlund L, Hedegaard B, et al. Dose titration study of tinzaparin, a low molecular weight heparin, in patients on chronic hemodialysis. Artif Organs 1998; 22: 633-7
74. Ryan KE, Lane DA, Flynn A, et al. Dose finding study of low molecular weight heparin, innohep, in haemodialysis. Thromb Haemost 1991; 66: 277-82
75. Koutsikos D, Fourtounas C, Kapetanaki A, et al. A cross-over study of a new low molecular weight heparin (Logiparin®) in hemodialysis. Int J Artif Organs 1996; 19: 467-71
76. Lord H, Jean N, Dumont M, et al. Comparison between tinzaparin and standard heparin for chronic hemodialysis in a Canadian center. Am J Nephrol 2002; 22 (1): 58-66
77. Beijering RJR, ten Cate H, Stevens P, et al. Randomised long-term comparison of tinzaparin and dalteparin in haemodialysis. Clin Drug Invest 2003; 23 (2): 85-97
78. Elisaf MS, Germanos NP, Bairaktari HT, et al. Effects of conventional vs. low-molecular-weight heparin on lipid profile in hemodialysis patients. Am J Nephrol 1997; 17: 153-7
79. Caro JJ, Getsios D, Caro I, et al. Cost effectiveness of tinzaparin sodium versus unfractionated heparin in the treatment of proximal deep vein thrombosis. Pharmacoeconomics 2002; 20 (9): 593-602
80. Hull RD, Raskob GE, Rosenbloom D, et al. Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs intravenous heparin: an economic perspective. Arch Intern Med 1997; 157; 289-94
81. Hoffmeyer U, Lewis D, Minhas N, et al. Economic evaluation of the use of Innohep in the treatment of acute pulmonary embolism. J Med Econ 1998; 1: 148-62
82. Valette F, Hoffmeyer U, Lloyd A. Economic evaluation of the use of tinzaparin in the treatment of deep vein thrombosis. Br J Med Econ 1995; 8: 111-23
83. Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation: an economic perspective. Arch Intern Med 1997; 157: 298-303
84. Wimperis JZ, Pout G, Dilks G, et al. Significant bed savings resulting from outpatient management of DVT with LMWH [abstract no. 231], Br J Haematol 1998 May; 101: 80
85. Wade WE, Spruill WJ. Cost comparison of tinzaparin versus enoxaparin as deep venous thrombosis prophylaxis in spinal cord injury: preliminary data. Blood Coagul Fibrinolysis 2001 Dec; 12 (8): 619-25
86. Strauss WE, Cain VA, Assaid CA, et al. Risk of bleeding events with tinzaparin or unfractionated heparin used as treatment for venous thromboembolic disease in patients with renal insufficiency [abstract no. P2331], 18th Congress of the International Society on Thrombosis and Haemostasis; 2001 Jul 6-12; Paris
87. Pautas E, Gouin I, Bellot O, et al. Safety profile of tinzaparin administered once daily at a standard curative dose in two hundred very elderly patients. Drug Saf 2002; 25 (10): 725-33
88. Christiansen HM, Rudlassen M, Borris LC, et al. Biological tolerance of logiparin, a low molecular weight heparin used in patients undergoing total hip replacement. Semin Thromb Hemost 1991; 17 Suppl. 2: 224-7
89. Christiansen HM, Lassen MR, Borris LC, et al. Biologic tolerance of two different low molecular weight heparins. Semin Thromb Hemost 1991; 17 (4): 450-4
90. Dalsgaard J. Treatment of venous thromboembolism with tinzaparin during pregnancy [abstract no. ER075]. Ann Hematol 1999; 78 Suppl. 1: A3
91. Jørgensen M, Landorph A, Dalsgaard Nielsen J. The low molecular weight heparin, tinzaparin, is effective and safe as thromboembolic prophylaxis during pregnancy [abstract no. O44]. Pathophysiol Haemost Thromb 2002; 32 Suppl. 2; 49
92. Leo Laboratories Limited. Innohep 10,000 IU/ml and innohep syringe 10,000 IU/ml [online]. Available from URL: http:// emc.medicines.org.uk/ [Accessed 2004 Mar 22]
93. Leo Pharma Inc. Product monograph innohep (tinzaparin sodium injection) anticoagulant/antithrombotic agent [online]. Available from URL: http://www.leopharma.ca [Accessed 2004 Jun 8]
94. Leo Laboratories Limited. Innohep 20,000 IU/ml and Innohep syringe 20,000 IU/ml [online]. Available from URL: http:// emc.medcines.org.uk/ [Accessed 2004 Mar 22]
95. Scottish Intercollegiate Consensus Guidelines Network. Prophylaxis of venous thromboembolism: a national clinical guideline [online]. Available from URL: http:// www.sign.ac.uk/pdf/sign62.pdf [Accessed 2004 Mar 19]
96. Turkstra F, Koopman MMW, Büller HR. The treatment of deep vein thrombosis and pulmonary embolism. Thromb Haemost 1997; 78: 489-96
97. Institute for Clinical Systems Improvement. ICSI health care guideline: venous thromboembolism [online]. Available from URL: http://www.icsi.org/ knowledge/ [Accessed 2004 Mar 17]
98. Hyers TM, Agnelli G, Hull RD, et al. Antithrombotic therapy for venous thromboembolic disease. Chest 2001; 119: 176-193S
99. White RH, Ginsberg JS. Low-molecular-weight heparins: are they all the same? Br J Haematol 2003 Apr; 121 (1): 12-20
100. Wade WE, Martin BC, Kotzan JA, et al. Formulary management of low molecular weight heparins. Pharmacoeconomics 2000; 17: 1-12
101. US Renal Data System. USDRS annual data report. National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, MD [online]. Available from URL: http://www.usrds.org/ [Accessed 2004 Jun 11]