REOPRO- abciximab injection, solution
Janssen Biotech, Inc.
For intravenous administration
Abciximab, ReoPro� , is the Fab fragment of the chimeric human-murine monoclonal antibody 7E3. Abciximab binds to the glycoprotein (GP) IIb/IIIa receptor of human platelets and inhibits platelet aggregation. Abciximab also binds to the vitronectin (αv β3 ) receptor found on platelets and vessel wall endothelial and smooth muscle cells.
The chimeric 7E3 antibody is produced by continuous perfusion in mammalian cell culture. The 47,615 dalton Fab fragment is purified from cell culture supernatant by a series of steps involving specific viral inactivation and removal procedures, digestion with papain and column chromatography.
ReoPro� is a clear, colorless, sterile, non-pyrogenic solution for intravenous (IV) use. Each single use vial contains 2 mg/mL of Abciximab in a buffered solution (pH 7.2) of 0.01 M sodium phosphate, 0.15 M sodium chloride and 0.001% polysorbate 80 in Water for Injection. No preservatives are added.
General - Abciximab binds to the intact platelet GPIIb/IIIa receptor, which is a member of the integrin family of adhesion receptors and the major platelet surface receptor involved in platelet aggregation. Abciximab inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor, and other adhesive molecules to GPIIb/IIIa receptor sites on activated platelets. The mechanism of action is thought to involve steric hindrance and/or conformational effects to block access of large molecules to the receptor rather than direct interaction with the RGD (arginine-glycine-aspartic acid) binding site of GPIIb/IIIa.
Abciximab binds with similar affinity to the vitronectin receptor, also known as the αv β3 integrin. The vitronectin receptor mediates the procoagulant properties of platelets and the proliferative properties of vascular endothelial and smooth muscle cells. In in vitro studies using a model cell line derived from melanoma cells, Abciximab blocked αv β3 -mediated effects including cell adhesion (IC50 = 0.34 μg/mL). At concentrations which, in vitro , provide > 80% GPIIb/IIIa receptor blockade, but above the in vivo therapeutic range, Abciximab more effectively blocked the burst of thrombin generation that followed platelet activation than select comparator antibodies which inhibit GPIIb/IIIa alone (1). The relationship of these in vitro data to clinical efficacy is unknown.
Abciximab also binds to the activated Mac-1 receptor on monocytes and neutrophils (2). In in vitro studies, Abciximab and 7E3 IgG blocked Mac-1 receptor function as evidenced by inhibition of monocyte adhesion (3). In addition, the degree of activated Mac-1 expression on circulating leukocytes and the numbers of circulating leukocyte-platelet complexes has been shown to be reduced in patients treated with Abciximab compared to control patients (4). The relationship of these in vitro data to clinical efficacy is uncertain.
INDICATIONS AND USAGE:
Abciximab is indicated as an adjunct to percutaneous coronary intervention for the prevention of cardiac ischemic complications
in patients undergoing percutaneous coronary intervention
in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours