Abciximab dosage, uses, trade name and its action

Description of Abciximab

Abciximab was the first FDA-approved platelet glycoprotein IIb/IIIa inhibitor. It is the Fab fragment of the chimeric monoclonal antibody 7E3. The substitution of human IgG for the murine IgG molecule produces a Fab fragment that causes fewer allergic and thrombocytopenic complications. Abciximab was FDA-approved in December 1994. In November 1997, the FDA expanded the indications for abciximab to a broader range of patients undergoing PCI, including those with unstable angina not responding to conventional therapy.

Mechanism of Action of Abciximab

Abciximab is a noncompetitive inhibitor of glycoprotein (GP) IIb/IIIa preventing the binding of fibrinogen,von Willebrand factor (vWF), and other adhesive ligands to the GP IIb/IIIa receptor on activated platelets. “Integrins”, which are found on virtually all cell types, are a family of adhesion molecules that mediate many physiologic responses. Unlike many of the other integrins, GP IIb/IIIa is platelet specific and is the most abundant receptor found on activated platelets, with about 50,000—80,000 copies/cell. Fibrinogen is the principal ligand to bind to the GP IIb/IIIa receptor. The binding of fibrinogen and other ligands, such as vWF, to the GP IIb/IIIa receptor results in cross-linking between platelets and is the final common pathway of platelet aggregation, which ultimately leads to thrombus formation. The mechanism of abciximab is believed to involve steric hindrance and/or conformational effects to block the access of fibrinogen and vWF to GP IIb/IIIa receptor sites. Blockade of the receptor sites subsequently prevents platelet aggregation. Maximal inhibition of platetet aggregation occurs when >= 80% of GP IIb/IIIa receptors are blocked by abciximab.

Abciximab not only binds GP IIb/IIIa, but also other integrins such as the vitronectin receptor. The vitronectin receptor has a regulatory role in the processes of cell adhesion, migration, and proliferation; it is also upregulated under conditions of rapid vascular growth, such as angiogenesis. Inhibition of vitronectin-induced cell proliferation may have a role in the prevention of restenosis; however, the long-term benefits of vitronectin inhibition have not been proven. Abciximab can act as an anticoagulant. Abciximab anticoagulant activity may be due to potent GP IIb/IIIa activity or the vitronectin receptor may be involved.

Pharmacokinetics of Abciximab

Abciximab is administered by intravenous bolus injection followed by intravenous infusion. Data describing abciximab’s metabolism are not available. The initial elimination half-life of free abciximab plasma concentrations is less than 10 minutes, with a second-phase half-life of about 30 minutes. Intravenous administration of a bolus dose of abciximab followed by continuous infusion according to recommended doses produces approximately constant free plasma concentrations throughout the infusion. At the termination of the infusion period, free plasma concentrations fall rapidly for approximately 6 hours then decline at a slower rate. Low levels of GP IIb/IIIa receptor blockade may be present for more than 10 days following discontinuation of the abciximab infusion. Platelet function generally recovers over the course of 48 hours despite the fact that abciximab remains in the circulation at low levels for more than 10 days.

Route-Specific Pharmacokinetics
Intravenous Route
Data are limited regarding the distribution of abciximab; however, the pharmacodynamic effects of the drug are well described. A bolus intravenous dose of abciximab is rapidly bound to platelet receptors and increases median bleeding time from about 5 minutes to over 30 minutes. Two hours after a bolus dose, over 80% of glycoprotein (GP) IIb/IIIa receptors are blocked and platelet aggregation is almost nonexistent. Blockade of >= 80% of GP IIb/IIIa receptors can be maintained by administration of a 0.125 mcg/kg/minute (maximum of 10 mcg/minute) continuous IV infusion. A lower continuous infusion dose was found insufficient to maintain the initial response. When an infusion of abciximab is stopped, there is an initial rapid decline in plasma concentrations over the first 6 hours, followed by a slower decline. Bleeding time usually declines to <= 12 minutes within 12 hours of discontinuation in about 75% of patients and within 24 hours in about 90% of patients. Ex vivo platelet aggregation in response to 20 mcM adenosine diphosphate returns to >= 50% of baseline within 24 hours in about 62% of patients and within 48 hours in roughly 88% of patients.

Generic Name
Abciximab

Brand Names
Reopro

Therapeutic Class
Monoclonal Antibody Fragment
Platelet Aggregation Inhibitor

FDA-Label Indications
Myocardial ischemia; Prophylaxis – Percutaneous coronary intervention; Adjunct: Adult
Percutaneous coronary intervention; Adjunct – Refractory angina, Unstable: Adult

Common Effects
Cardiovascular: Chest pain (11.4% ), Hypotension (14.4% )
Dermatologic: Injection site pain (3.6% )
Gastrointestinal: Abdominal pain (3.1% ), Nausea (13.6% ), Vomiting (7.3% )
Hematologic: Hemorrhage (0.8% to 16.8% )
Musculoskeletal: Backache (17.6% )

Serious Effects
Hematologic: Thrombocytopenia, Any Severity (2.5% to 5.2% ), Thrombocytopenia, Severe (0.4% to 1% )
Immunologic: Anaphylaxis, Antibody development, Hypersensitivity reaction
Neurologic: Cerebrovascular accident, Nonhemorrhagic, Intracranial hemorrhage
Respiratory: Pulmonary hemorrhage, Alveolar

Administration
Intravenous: Use a sterile, non-pyrogenic, low protein-binding syringe filter (0.2 or 5 micron) for bolus injection or admixture, or use an in-line 0.2 or 0.22 micron filter for continuous infusion
Intravenous: Continuous infusion: Dilute in NS or D5W; do not shake
Intravenous: Continuous infusion: Infuse at a maximum rate of 10 mcg/min
Intravenous: Do not mix with other medications

Adult Dose
Acute myocardial infarction – Cardiogenic shock: 0.25 mg/kg by IV bolus, followed by a 12-hour infusion of 10 mcg/minute (study dosage)
Arterial thrombosis, acute: 0.25 mg/kg IV bolus followed by an infusion of 0.125 mcg/kg/min for 12 hours (MAX, 10 mcg/min) as an adjunct to thrombolytic therapy (study dosage)
Myocardial infarction: 0.25 mg/kg IV bolus over 5 minutes followed by 0.125 mcg/kg/min (MAX 10 mcg/min) IV infusion for 12 hours in combination with reduced-dose fibrinolytic therapy (study dosage)
Myocardial ischemia; Prophylaxis – Percutaneous coronary intervention; Adjunct: initial bolus, 0.25 mg/kg IV over 5 minutes 10 to 60 minutes prior to angioplasty
Myocardial ischemia; Prophylaxis – Percutaneous coronary intervention; Adjunct: maintenance infusion, 0.125 mcg/kg/min (MAX 10 mcg/min) IV for 12 hours unless complications
Myocardial ischemia; Prophylaxis – Percutaneous coronary intervention; Adjunct: (intracoronary administration) 0.25 mg/kg bolus
Percutaneous coronary intervention; Adjunct – Refractory angina, Unstable: start within 24 hours before percutaneous coronary intervention (PCI), 0.25 mg/kg IV bolus followed by an IV infusion of 10 mcg/min for 18 to 24 hours, concluding 1 hour after the PCI

Pediatric Dose
General Dosage Information: safety and effectiveness in pediatric patients have not been established
Aneurysm of coronary vessels – Kawasaki disease: 0.25 mg/kg IV bolus over 30 minutes, then 0.125 mcg/kg/minute for 12 hours (guideline dosage)
Aneurysm of coronary vessels – Kawasaki disease: Concomitant therapy, substantial thrombus burden with high risk of occlusion: May be coadministered with reduced-dose alteplase (guideline dosage)