Aparin [Sandoz, a division of Novartis group] utilizing the generic drug > 자유게시판

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Aparin [Sandoz, a division of Novartis group] utilizing the generic drug pathway. On the other hand, the EMEA has considered these agents to be biosimilar. Furthermore, the EMEA stated that biosimilar versions of LMWHs should be considered biological medicinal products and may not be submitted 4CzIPN for approval as generic medicinal products. In a concept guideline manuscript, the EMEA considers the heterogeneity of LMWH to be very high, and recommends clinical trials to demonstrate equivalence of biosimilar LMWHs [11]. Thus there is a regulatory discordance between the EMEA and US FDA. As the biosimilar LMWHs have only recently been produced there is limited clinical data available with which to compare the biosimilar and branded versions. The available data from pharmacological in vitro or preclinical studies using anticoagulation profiles and neutralization with protamine sulfate as their primary outcomes differentiate branded from biosimilar LMWHs. Biosimilar and branded versions of enoxaparin [66,67] and dalteparin [67] differ in their responses to the inhibitor protamine sulfate, the composition of their oligosaccharide chains [66,67], their affinity for AT [67], and their immunogenic potential [68]. The differences in assay-responses become more pronounced at higher concentrations: for example, at prophylactic doses the anticoagulant levels of the branded and biosimilar enoxaparin appear similar but at treatment doses enoxaparin exhibits significantly greater anticoagulant effects Phenyl (4-chloro-3-fluorophenyl)carbamate [66]. Similar dose-dependent variations have been reported in the response to neutralization with protamine sulfate [67].Anticoagulants in development (Ultra-)LMWHs are currently being developed for different indications, amongst others bemiparin (Rovi, Madrid, Spain) and semuloparin (sonofi-aventis, Paris, France). Due to PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3081428 the clinical and practical limitations of warfarin, new oral anticoagulants to replace warfarin have also been sought. Oral vitamin K antagonists (warfarin) are used for long-term anticoagulation [6,7]. The first of the new oral anticoagulants was the oral direct thrombin inhibitor ximelagatran. However, this drug was withdrawn from use soon after it was licensed due to evidence of its potential hepatotoxicity. Two secondgeneration direct oral Factor Xa inhibitors ivaroxaban, which has been approved in the EU and Canada, and apixaban re currently in the final stages of clinical development. Based on the ximelagatran experience, clinical vigilance is required to determine the long-term safety of these agents. Dabigatran is another novel oral anticoagulant which has received recent approval in some European countries, Canada and recently in US; dabigatran is a direct thrombin inhibitor, administered orally as a double prodrug formulation (dabigatran etexilate). However, while this drug is approved in EMEA for post orthopedic surgical thromboprophylaxis, in PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/3971254 the US, it is approved for stroke prevention in atrial fibrillation. Several other oral anticoagulants such as edoxaban, betrixiban are also in clinical development. A parenteral anti Xa agent with strong anticoagulant activity namely Otamixaban (sonofi-aventis, Paris, France) is also in advanced clinical stages as a parenteral anticoagulant in percutaneous intervention. New anticoagulants completing clinical development are not supported by the depth of clinical evidence that is available for the currently recommended anticoagulants in terms of clinical experience or the range of patient p.