Top

Published in:

01-08-2002 | Original Research Article

Safety Profile of Tinzaparin Administered Once Daily at a Standard Curative Dose in Two Hundred Very Elderly Patients

Authors: Eric Pautas, Isabelle Gouin, Oliver Bellot, Jean-Paul Andreux, Dr Virginie Siguret

Published in: Drug Safety | Issue 10/2002

Abstract

Objectives: Too few very elderly patients with an age-related renal impairment are included in clinical trials. We conducted a study in order to evaluate the safety profile of tinzaparin, a low molecular weight heparin (LMWH), given at a curative dose (175 IU/kg once daily) in very elderly patients treated for up to 30 days.

Setting: An 800-bed geriatric hospital.

Design: A 1-year prescribing study.

Patients: Consecutive in-patients older than age 70, whose creatinine clearance was above 20 ml/min, and requiring full anticoagulation with LMWH were included.

Measurements: Safety parameters (major bleeding/heparin-induced thrombocytopenia/death) were recorded. Plasma anti-Xa activity levels were regularly measured throughout the treatment period.

Results: Two-hundred in-patients, mean age 85.2 ± 6.9 years (70 to 102), mean creatinine clearance 51.2 ± 22.9 ml/min, were given tinzaparin. Six patients died during the treatment period: only one could be related to the anticoagulation treatment. Three major bleeding episodes (1.5%) were reported. Antithrombotic drug interactions likely contributed to the bleeding event in two of them. Heparin-induced thrombocytopenia was confirmed in two patients (1%). No correlation was found between anti-Xa activity and creatinine clearance or age.

Conclusions: Tinzaparin can be used safely at a curative dose in very elderly patients as long as (i) the accurate bodyweight-adjusted dose is given; (ii) platelet counts and anti-Xa levels are regularly monitored and; (iii) the interaction with other antithrombotic drugs is correctly managed.

The use of tradenames is for product identification purposes only and does not imply endorsement.

Kniffin WD, Baron JA, Barrett J. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994; 154: 861–6PubMedCrossRef

Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implications. Arch Intern Med 1995; 155: 469–73PubMedCrossRef

Hirsh J. Guide to anticoagulant therapy: heparin. Circulation 2001; 103: 2994–3018PubMedCrossRef

Leizorovicz A, Simonneau G, Decousus H, et al. Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 1994; 309: 299–304PubMedCrossRef

Lensing AWA, Prins MH, Davidson BL, et al. Treatment of deep venous thrombosis with low-molecular-weight heparins. Arch Intern Med 1995; 155: 601–7PubMedCrossRef

Siragusa S, Cosmi B, Piovella F, et al. Low molecular weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a metaanalysis. Am J Med 1996; 100: 269–77PubMedCrossRef

Gould MK, Dembitzer AD, Doyle RL, et al. Low molecular weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. Ann Intern Med 1999; 130: 800–9PubMed

Dolovich LR, Ginsberg JS, Douketis JD, et al. A meta-analysis comparing low molecular weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 2000; 160: 181–8PubMedCrossRef

Couturaud F, Julian JA, Kearon C. Low molecular weight heparin administered once versus twice daily in patients with venous thromboembolism: ameta-analysis. Thromb Haemost 2001; 86: 980–4PubMed

10.

Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low molecular weight heparins. Chest 2001; 119: 64S–94SPubMedCrossRef

11.

Epstein M. Aging and the kidneys. J Am Soc Nephrol 1996; 7: 1106–22PubMed

12.

The Thrombolysis In Myocardial Infarction (TIMI) 11A trial investigators. Dose-ranging trial of enoxaparin for unstable angina: results of TIMI 11A. J Am Coll Cardiol 1997; 29: 1474–82

13.

Bratt G, Törnebohm E, Granqvist S, et al. A comparison between low molecular weight heparin (Kabi 2165) and standard heparin in the intravenous treatment of deep venous thrombosis. Thromb Haemost 1985; 54: 813–7PubMed

14.

Abbate R, Gori AM, Farsi A, et al. Monitoring of low molecular weight heparins in cardiovascular disease. Am J Cardiol 1998; 82: 331–61CrossRef

15.

Boneu B, de Moerloose P. How and when to monitor a patient treated with low molecular weight heparin. Semin Thromb Haemost 2001; 27: 519–22CrossRef

16.

Mismetti P, Laporte-Simitsitis S, Navarro C, et al. Aging and venous thromboembolism influence the pharmacodynamics of the anti-factor Xa and anti-thrombin activities of a low molecular weight heparin (nadroparin). Thromb Haemost 1998; 79: 1162–5PubMed

17.

Sanderink GJ, Guimart CG, Ozoux ML, et al. Pharmacokinetics and pharmacodynamics of the prophylactic dose of enoxaparin once daily over 4 days in patients with renal impairment. Thromb Res 2002; 105: 225–31PubMedCrossRef

18.

Merli GJ. Treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin in the geriatric patient population. Clin Geriatr Med 2001; 17: 93–106PubMedCrossRef

19.

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–42PubMedCrossRef

20.

Tinzaparin French summary product characteristics. 76th rev ed. Vidal Dictionary. Paris: Vidal ed, 2000

21.

Barrett JS, Hainer JW, Kornhauser DM, et al. Anticoagulant pharmacodynamics of tinzaparin following 175 iu/kg subcutaneous administration to healthy volunteers. Thromb Res 2001; 101(4): 243–54PubMedCrossRef

22.

Cambus JP, Saivin S, Heilmann JJ, et al. The pharmacodynamics of tinzaparin in healthy volunteers. Br J Haematol 2002; 116: 649–52PubMedCrossRef

23.

Barrett JS, Gibiansky E, Hull RD, et al. Population pharmacodynamics in patients receiving tinzaparin for the prevention and treatment of deep vein thrombosis. Int J Clin Pharmacol Ther 2001; 39: 431–46PubMed

24.

Siguret V, Pautas E, Février M, et al. Elderly patients treated with tinzaparin (Innohep®) administered once daily (175 anti-Xa IU/kg): anti-Xa and anti-IIa activities over 10 days. Thromb Haemost 2000; 84: 800–4PubMed

25.

Elalamy I, Lecrubier C, Potevin F, et al. Absence of in vitro cross-reaction of pentasaccharide with the plasma heparin dependant factor of 25 patients with heparin-associated thrombocytopenia. Thromb Haemost 1995; 74: 1379–87

26.

Manckoundia P, Zarouala B, Lalu-Fraisse A, et al. Muscle hematoma in the very elderly receiving low-molecular weight heparins [letter in French]. Presse Med 2000; 29: 702PubMed

27.

Dear Doctor Letter. LMWHs [in French]. French Drug Agency, 2001 Sep 1

28.

Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975–82PubMedCrossRef

29.

Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin for acute pulmonary embolism. N Engl J Med 1997; 337: 663–9PubMedCrossRef

30.

Tardy-Poncet B, Tardy B. Heparin induced thrombocytopenia: minimising the risks in the elderly patient. Drugs Aging 2000; 16: 351–4PubMedCrossRef

31.

Warkentin TE. Heparin-induced thrombocytopenia: a clinicopathologic syndrome. Thromb Haemost 1999; 82: 439–47PubMed

32.

Palareti G, Hish J, Legnani C, et al. Oral anticoagulation in the elderly. Arch Intern Med 2000; 160: 470–8PubMedCrossRef

33.

Veiga F, Escriba A, Maluenda MP, et al. Low molecular weight heparin (enoxaparin) versus oral anticoagulant therapy (acenocoumarol) in the long-term treatment of deep venous thrombosis in the elderly: a randomized trial. Thromb Haemost 2000; 84: 559–64PubMed

34.

Hull RD, Pineo GF, Mah AF, et al. Home-LITE: 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 weight heparin versus warfarin [abstract no. 1647]. Thromb Haemost 2001; 86Suppl.

35.

Breddin HK, Hach-Wunderle V, Nakov R, et al. Effects of a low molecular weight heparin on thrombus regression and recurrent thromboembolism in patients with deep vein thrombosis. N Engl J Med 2001; 344: 626–31PubMedCrossRef

36.

Monreal M, Roncales FJ, Ruiz J, et al. Secondary prevention of venous thromboembolism: a role for low molecular weight heparin. Haemostasis 1998; 28: 236–43PubMed

Title: Safety Profile of Tinzaparin Administered Once Daily at a Standard Curative Dose in Two Hundred Very Elderly Patients
Authors: Eric Pautas
Isabelle Gouin
Oliver Bellot
Jean-Paul Andreux
Dr Virginie Siguret
Publication date: 01-08-2002
Publisher: Springer International Publishing
Published in: Drug Safety / Issue 10/2002
Print ISSN: 0114-5916
Electronic ISSN: 1179-1942
DOI: https://doi.org/10.2165/00002018-200225100-00005

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Safety Profile of Tinzaparin Administered Once Daily at a Standard Curative Dose in Two Hundred Very Elderly Patients

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2002

Regulatory Decisions in a Globalised World

Aspirin and Reye’s Syndrome

Detection of Adverse Drug Reactions in a Neurological Department

Drug Interactions with Tacrolimus

How Safe is Emergency Contraception?

A New Poisson and Bayesian-Based Method to Assign Risk and Causality in Patients with Suspected Hepatic Adverse Drug Reactions