INDICATIONS

ReoPro® (abciximab) is indicated as an adjunct to percutaneous coronary intervention (PCI) for the prevention of cardiac ischemic complications:

  • In patients undergoing PCI
  • In patients with UA not responding to conventional medical therapy when PCI is planned within 24 hours

Safety and efficacy of ReoPro use in patients not undergoing PCI have not been established. ReoPro is intended for use with aspirin and heparin and has been studied only in that setting, as described in clinical studies.

Important Safety Information

CONTRAINDICATIONS

  • Active internal bleeding
  • Recent (within 6 weeks) gastrointestinal (GI) or genitourinary (GU) bleeding of clinical significance
  • History of cerebrovascular accident (CVA) within 2 years, or CVA with a significant residual neurological deficit
  • Bleeding diathesis
  • Administration of oral anticoagulants within 7 days unless prothrombin time ≤1.2 times control
  • Thrombocytopenia (<100,000 cells/μL)
  • Recent (within 6 weeks) major surgery or trauma
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Severe uncontrolled hypertension
  • Presumed or documented history of vasculitis
  • Use of intravenous dextran before percutaneous coronary intervention, or intent to use it during intervention
  • Known hypersensitivity to any component of this product or to murine proteins

WARNINGS

Bleeding Risk

ReoPro has the potential to increase the risk of bleeding, particularly in the presence of anticoagulation agents, for example, from heparin or other anticoagulants. The risk of a major bleed due to ReoPro therapy is increased in patients receiving thrombolytics and should be weighed against the anticipated benefits. In the EPILOG and EPISTENT trials, the incidence of major bleeding in patients receiving ReoPro and low-dose heparin was similar to placebo levels.

ISI Graph 1

  1. Patients who had bleeding in more than one classification are counted only once according to the most severe classification. Patients with multiple bleeding events of the same classification are also counted once within that classification
  2. Standard-dose heparin with or without stent (EPILOG and EPISTENT)
  3. Low-dose heparin with or without stent (EPILOG and EPISTENT)
  4. Standard-dose heparin (EPILOG)

ALLERGIC REACTIONS (including anaphylaxis)

Allergic reactions, some of which were anaphylaxis (sometimes fatal), have been reported rarely in patients treated with ReoPro. Patients with allergic reactions should receive appropriate treatment. Treatment of anaphylaxis should include immediate discontinuation of ReoPro administration and initiation of resuscitative measures.

PRECAUTIONS

Thrombocytopenia

In clinical trials, patients treated with ReoPro were more likely than patients who received placebo to experience decreases in platelet counts (also see Readministration).

ISI Graph 2

Modestly lower rates were observed among patients treated with placebo plus standard-dose heparin.

Readministration of ReoPro

Administration of ReoPro may result in the formation of human anti-chimeric antibodies (HACA) that could potentially cause allergic or hypersensitivity reactions (including anaphylaxis), thrombocytopenia, or diminished benefit upon readministration. In a registry study of ReoPro readministration (1342 treatments in 1286 patients), there were no reports of serious allergic reactions or anaphylaxis. Thrombocytopenia was observed at higher rates in the readministration study than in the phase 3 studies of first-time administration, suggesting that readministration may be associated with an increased incidence and severity of thrombocytopenia. This increased risk was associated with a history of thrombocytopenia on prior ReoPro exposure, a positive HACA assay at baseline, and readministration within 30 days.

Guidelines for Reduction in Bleeding

  • Use of a low-dose, weight-adjusted heparin regimen
  • Discontinuation of heparin on completion of the procedure with removal of the arterial sheath within 6 hours
  • Careful vascular access site management and careful patient management, including attention to other potential bleeding sites
  • Use of a weight-adjusted bolus and continuous infusion dose of ReoPro measures should be initiated

DOSAGE & ADMINISTRATION

The safety and efficacy of ReoPro have only been investigated with concomitant administration of heparin and aspirin as described in CLINICAL STUDIES. Please see the full prescribing information for detailed information.

As an adjunct to PCI:

ReoPro® (abciximab) intravenous bolus plus infusion

  • - IV bolus 0.25 mg/kg 10 to 60 minutes before PCI followed by
  • - IV infusion 0.125 mcg/kg/minute (max of 10 mcg/minute) for 12 hours

Onset and Reversibility

Onset The onset of ReoPro following a 0.25 mg/kg bolus dose (plus 0.125 mcg/kg/minute infusion) is rapid with the inhibitory effects evident within 10 minutes. Low levels of GP IIb/IIIa receptor blockade are present for more than 10 days following cessation of the infusion.

Reversibility Upon discontinuation of therapy with ReoPro, bleeding time returns to less than or equal to 12 minutes within 12 hours. Inhibitory effects of ReoPro can be rapidly reversed, at least in part, with platelet transfusions.

For additional safety information, please consult the Important Safety Information or the Prescribing Information for ReoPro.

Safety

Bleeding

ReoPro has the potential to increase the risk of bleeding, particularly in the presence of anticoagulation agents.

Major Bleeding in Randomized Trials

Major Bleeding in ReoPro Registration Trials

ACC/AHA STEMI Guidelines state that when GP IIb/IIIa inhibitors are used, the UFH bolus should be reduced to achieve a target ACT of 200 seconds.6

Bleeding rates were reduced in the CAPTURE trial, and further reduced in the EPILOG and EPISTENT trials by use of modified dosing regimens and specific patient management techniques.3,8,9

References:

  1. Brener SJ, Barr LA, Burchenal JE, et al, on behalf of the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation. 1998; 98:734-741.
  2. Montalescot G, Barragan P, Wittenberg O, et al, for the ADMIRAL Investigators. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med. 2001; 344:1895-1903.
  3. Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycomprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation. 1998; 98:2695-2701.
  4. Neumann FJ, Kastrati A, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction. J Am Coll Cardiol. 2000; 35:915-921.
  5. Stone GW, Grines CL, Cox DA, et al, for the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med. 2002; 346:957-966.
  6. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004; 110:e82-e293.
  7. Lincoff AM, Califf RM, Anderson KM, for the EPIC Investigators. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab (c7E3 Fab) among patients with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol. 1997; 30:149-156.
  8. The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet. 1997; 349:1429-1435.
  9. The Epilog Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N. Engl J. Med. 1997; 336:1689-1697.
  10. Epistent Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Lancet. 1998; 352:87-92.