Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brazil.
Thromb Haemost. 2012 Feb;107(2):302-14. doi: 10.1160/TH11-09-0664. Epub 2012 Jan 11.
Patent protection for enoxaparin has expired. Generic preparations are developed and approved for clinical use in different countries. However, there is still skepticism about the possibility of making an exact copy of the original drug due to the complex processes involved in generating low-molecular-weight heparins. We have undertaken a careful analysis of generic versions of enoxaparin available for clinical use in Brazil. Thirty-three batches of active ingredient and 70 of the final pharmaceutical product were obtained from six different suppliers. They were analysed for their chemical composition, molecular size distribution, in vitro anticoagulant activity and pharmacological effects on animal models of experimental thrombosis and bleeding. Clearly, the generic versions of enoxaparin available for clinical use in Brazil are similar to the original drug. Only three out of 33 batches of active ingredient from one supplier showed differences in molecular size distribution, resulting from a low percentage of tetrasaccharide or the presence of a minor component eluted as monosaccharide. Three out of 70 batches of the final pharmaceutical products contained lower amounts of the active ingredient than that declared by the suppliers. Our results suggest that the generic versions of enoxaparin are a viable therapeutic option, but their use requires strict regulations to ensure accurate standards.
依诺肝素的专利保护已经过期。许多国家已经开发并批准了仿制药用于临床。但是，由于生产低分子肝素的过程复杂，人们对仿制原药的可能性仍然持怀疑态度。我们仔细分析了在巴西临床使用的依诺肝素仿制药。从六个不同的供应商处获得了 33 批原料药和 70 批成品药。对它们的化学成分、分子大小分布、体外抗凝活性以及在实验性血栓形成和出血动物模型中的药理作用进行了分析。显然，在巴西临床使用的依诺肝素仿制药与原药相似。只有来自一个供应商的 33 批原料药中的三批显示出分子大小分布的差异，这是由于四糖的低百分比或存在作为单糖洗脱的次要成分所致。70 批成品药中的三批所含的活性成分低于供应商所宣称的数量。我们的结果表明，依诺肝素的仿制药是一种可行的治疗选择，但它们的使用需要严格的监管，以确保准确的标准。
