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 Approval1994SummaryAbciximab 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.References

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1. Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 325-338. 10.1172/JCI110973

2. Nurden AT, Poujol C, Durrieu-Jais C, Nurden P. Platelet glycoprotein IIb/IIIa inhibitors: basic and clinical aspects. Arterioscler Thromb Vasc Biol 1999; 19: 2835-2840.  

3. Tcheng JE, Kandzari DE, Grines CL, Cox DA, Effron MB et al. Benefits and risks of abciximab use in primary angioplasty for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial. Circulation 2003;108:1316-1323.

4. Starnes HB, Patel AA, Stouffer GA. Optimal use of platelet glycoprotein IIb/IIIa receptor antagonists in patients undergoing percutaneous coronary interventions. Drugs 2011; 71: 2009-2030.

5. Kastrati A, Neumann FJ, Schulz S, Massberg S, Byrne RA et al. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med 2011; 365 (21): 1980-1989.

6. Roffi M, Chew DP, Mukherjee D, Bhatt DL, White JA, Heeschen C et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation 2001;104:2767-2771.

7. De Rosa S, Caiazzo G, Torella D, Indolfi C. Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndrome: A meta-analysis of clinical trials. Int J Cardiol 2012; S0167-5273.

8. Thiele H, Wöhrle J, Hambrecht R. Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial.  Lancet. 2012; 379: 923-931.

9. Veloso TR, Que YA, Chaouch A, Giddey M, Vouillamoz J et al. Prophylaxis of Experimental Endocarditis With Antiplatelet and Antithrombin Agents: A Role for Long-term Prevention of Infective Endocarditis in Humans? J Infect Dis. 2014 Aug 1. pii: jiu426.

10. Salzler GG, Graham A, Connolly PH, Schneider DB, Meltzer AJ. Safety and Effectiveness of Adjunctive Intra-Arterial Abciximab in the Management of Acute Limb Ischemia. Ann Vasc Surg. 2016 Jan;30:66-71.