Original Article

Comparison of Generic (Rolexan) and Brand (Clexan) Forms of Enoxaparin in Critically Ill Patients: A Cross Over, Open Label, Randomized Prospective Clinical Trial

Abstract

Backgrounds: Several generic forms of enoxaparin were introduced to the market after expiring the patent of Clexane. But the main problem with generic forms is its bio-equivalency with brand form as a little difference in active ingredients characteristics, could led to significant clinical differences. For evaluating the efficacy of enoxaparin, it is recommended to measure its activity against Anti Xa. The aim of this study was comparison of Anti Xa Activity of Enoxan® versus Clexane ® in critically ill patients with prophylactic doses.
Methods: This was a cross over, open label, randomized prospective study which was performed between September 2016 and December 2017 in intensive care unit of Labbafinezhad hospital, Tehran, Iran. Thirty adult patients, who received enoxaparin for prophylaxis of thromboembolic events, were recruited. Subjects were subsequently randomized to one of the treatment sequences (Generic–brand or brand–generic). The generic drug was enoxaparin sodium 40 mg (4,000 IU anti-FXa/0.4 mL), manufactured by Ronakpharm, Iran; the brand drug was enoxaparin sodium 40 mg (Clexane® 4,000 IU anti-FXa/0.4 mL), manufactured by Sanofi, France.
Results: Anti-Xa activity was assessed with Stago kit. The anti-Xa activity between 0.2 and 0.5 U/mL was defined as prophylaxis. The average Anti-Xa activities of Clexan and Rolexan were 0.3±0.12 and 0.22±0.10, respectively which reveals statistically no significant difference (P: 0.35). Also Anti-Xa activity in 6 and 11 patients in Clexan and Rolexan groups were under 0.2 (P: 0.16).
Conclusion: Our study showed comparable efficacy of prophylactic doses between Clexan and Rolexan in critically ill patients. Further studies in different patient population are recommended.

1. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e24S-e43S.
2. Bergqvist D, Nilsson B, Hedner U, Pedersen PC, Ostergaard PB. The effect of heparin fragments of different molecular weights on experimental thrombosis and haemostasis. Thromb Res 1985;38(6):589-601.
3. Carter CJ, Kelton JG, Hirsh J, Cerskus A, Santos AV, Gent M. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982;59(6):1239-45.
4. Johnston A, Hsieh SC, Carrier M, et al. A systematic review of clinical practice guidelines on the use of low molecular weight heparin and fondaparinux for the treatment and prevention of venous thromboembolism: Implications for research and policy decision-making. PLoS One 2018;13(11):e0207410.
5. European Medicines Agency (EMA) Committee for Medicinal products for Human Use (CHMP). Guideline on non-clinical and clinical development of similar biological medicinal products containing low molecular-weight-heparins [pamphlet]. London: European Medicines Agency; 2016.
6. U.S. Food and Drug Administration (FDA). Draft Guidance on Enoxaparin Sodium[Internet]. U.S. Department of Health and Human Services:Washington;Oct 2011. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/psg/Enoxaparin_Inj_20164_RC10-11.pdf
7. Kesselheim AS, Eddings W, Raj T, et al. Physicians' Trust in the FDA's Use of Product-Specific Pathways for Generic Drug Approval. PLoS One 2016;11(10):e0163339.
8. Ofosu FA. The United States Food and Drugs Administration approves a generic enoxaparin. Clin Appl Thromb Hemost 2011;17(1):5-8.
9. European Medicines Agency and the European Commission. Biosimilars in the EU Information guide for healthcare professionals [pamphlet]. Amsterdam: European Medicines Agency; 2017.
10. Kurki P, van Aerts L, Wolff-Holz E, Giezen T, Skibeli V, Weise M. Interchangeability of Biosimilars: A European Perspective. BioDrugs 2017;31(2):83-91.
11. Kawalec P, Stawowczyk E, Tesar T, et al. Pricing and Reimbursement of Biosimilars in Central and Eastern European Countries. Front Pharmacol 2017;8:288.
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IssueVol 8, No 1 (Winter 2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/jpc.v8i1.2743
Keywords
Enoxaparin Clexan Rolexan Anti Xa Low Molecular Weight Heparin
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How to Cite
1.
Ziaie S, Malekmohammadi H, Sistanizad M. Comparison of Generic (Rolexan) and Brand (Clexan) Forms of Enoxaparin in Critically Ill Patients: A Cross Over, Open Label, Randomized Prospective Clinical Trial. J Pharm Care. 2020;8(1):23-25.