Compound Name:AbciximabMolecular Target:Glycoprotein (GP) IIb/IIIa receptor of human plateletsMolecular Structure:chimeric/human monoclonal antibody; Fab portionLicensed Indication:cardiac ischemiaManufacturer and/or Distributor:Centocor; Eli LillyInitial FDA Approval:1994Summary:
Abciximab is the purified Fab fragment product of the chimeric monoclonal antibody 7E3, which is targeted to bind to the GPIIb/IIIa receptor of human platelets. Abciximab therefore inhibits platelet aggregation by preventing the binding of pro-coagulants such as fibrinogen, von Willebrand factor, and others to the GPIIb/IIIa receptor sites on activated platelets. Abciximab also reduces platelet adhesion to other cell types via binding to the vitronectin receptor on platelets as well as endothelial and smooth muscle cells, and via binding to the activated macrophage antigen-1 integrin (Mac-1 receptor) located on granulocytes and monocytes.
In pre-licensing clinical trials, abciximab was found to reduce death, myocardial infarctions, and urgent intervention in patients at risk of thrombosis following percutaneous transluminal coronary angioplasty or atherectomy (PTCA). It was approved as an adjunct to percutaneous coronary intervention (PCI) for prevention of cardiac ischemic complications in these settings, and indications were expanded to include treatment of a broad range of patients undergoing PCI intervention and patients with unstable angina not responding to conventional medical therapy, when PCI is planned within 24 hours. High-risk patients with diabetes derive immediate and potentially long-term mortality benefits with abciximab. Contrary to expectations, clinical trials have indicated that the use of bolus intracoronary abciximab compared with bolus intravenous abciximab produced no improvement in the primary endpoint of death, new myocardial infarction or heart failure evaluated at 90 days.
Adverse reactions observed with abciximab therapy mainly involve excessive or abnormal bleeding, sometimes associated with thrombocytopenia. Thus, abciximab is contraindicated in a numbers of conditions that create an increased risk of hemorrhage. To minimize the risk of bleeding with abciximab, it is important to use weight-adjusted dosing of abciximab and low-dose weight adjusted doses of heparin, with adherence to stricter anticoagulation guidelines. Abciximab can cause hypersensitivity reactions including anaphylaxis, emergency drugs and equipment must always be available. Abciximab comes under Pregnancy Category C. It is not recommended for use in children.
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