Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version

Abstract

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.

Biosimilar versus branded enoxaparin to prevent postoperative venous thromboembolism after surgery for digestive tract cancer: Randomized trial

“…Enoxaparin Cristalia was as effective as branded enoxaparin to prevent VTED [ 38 ]. In 2020, Qneibi et al [ 21 ] concluded that Heparinox (a new biosimilar) was bioequivalent to the original branded enoxaparin based upon in vitro tests. In 2021, Fantoni et al [ 39 ] conducted an observational, retrospective study to assess the safety and effectiveness of Inhixa in preventing VTED in medical and surgical inpatients.…”

“…Several biosimilar versions of Lovenox ® (Sanofi, Paris, France), the original branded form of enoxaparin, have become available for clinical use for the indications that Lovenox ® was previously approved [ 21 ].…”

Perioperative Management of Dental Surgery Patients Chronically Taking Antithrombotic Medications

“…Two types of heparins are used in clinical practice: unfractionated heparins (UFH) and low molecular weight heparins (LMWH) [ 19 , 20 ].…”

“…When administered intravenously, the anticoagulant effect occurs immediately after injection. The drugs residence time depends on the administered dose and may range from 1–5 h. When injected subcutaneously, the anticoagulant effect occurs after 2–4 h [ 1 , 15 , 19 , 20 ].…”

“…Low molecular weight heparins are mainly used subcutaneously. After administration, the maximum anticoagulant effect occurs 2–3 h after administration and lasts up to 24 h [ 19 , 20 ].…”