Questions about Atrial Fibrillation? Get answers from our expert.

Abciximab (Systemic)


VA CLASSIFICATION
Primary: BL117
Secondary: CV900

Commonly used brand name(s): ReoPro®; ReoPro™.

Another commonly used name is
c7E3 Fab .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antithrombotic—

monoclonal antibody (antithrombotic)—

platelet aggregation inhibitor—

Indications

Accepted

Thrombosis, percutaneous coronary intervention–related (prophylaxis){01}{02}{04}{10}{17}—Abciximab is indicated as an adjunct to aspirin and heparin for the prevention of acute cardiac ischemic complications    • in patients undergoing percutaneous coronary intervention or
   • in patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours {01}.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Derived from the murine immunoglobulin G 1 monoclonal antibody, m7E3. {04}
Molecular weight—
    Approximately 47,600 daltons {03}

Mechanism of action/Effect:

Abciximab is a chimeric human-murine monoclonal antibody Fab (fragment antigen binding) fragment. {04} It inhibits platelet aggregation by specifically binding to the glycoprotein GPIIb/IIIa receptor, the major surface receptor involved in the final common pathway for platelet aggregation. {01} {04} {05} {06} {08} {12} Inhibition of platelet aggregation occurs in a dose-dependent manner. {12} {13} Abciximab binding to the GPIIb/IIIa receptor prevents fibrinogen, von Willebrand factor, vitronectin, and other adhesive molecules from binding to the receptor, thereby inhibiting platelet aggregation. {01} {04} {06} Abciximab is thought to block access of large molecules to the receptor by steric hindrance and/or conformational effects rather than interacting directly with the arginine-glycine-aspartic acid binding site of GPIIb/IIIa. {01}


Other actions/effects:

Abciximab may also bind to the vitronectin receptor and to the Mac-1 integrin receptor on activated monocytes. However, resulting clinical effects have not been identified. {04}

Half-life:

Cleared rapidly from plasma, with an initial phase half-life of less than 10 minutes and a second phase half-life of 30 minutes. {01} {04}

Duration of action:

Platelet function generally recovers within 48 hours; {01} {13} however, low levels of GPIIb/IIIa receptor blockade are present for 15 days or more after discontinuation of the infusion. {01}

Elimination:
    In general, Fab fragments are cleared more rapidly by the kidneys than are whole antibodies. {04} Abciximab is probably catabolized in a manner similar to that of other natural proteins. {04}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients with known sensitivity to murine monoclonal antibodies may also be sensitive to abciximab. {04} Patients who develop human anti-chimeric antibody (HACA) titers after abciximab therapy may have allergic or hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies. {01}

Carcinogenicity

Long-term studies evaluating the carcinogenic potential of abciximab have not been performed. {01}

Mutagenicity

In vitro and in vivo mutagenicity studies have not demonstrated any mutagenic effect. {01}

Pregnancy/Reproduction
Fertility—
Studies evaluating abciximab's effect on fertility in male or female animals have not been done. {01}

Pregnancy—
Studies have not been done in humans. {01}

Studies have not been done in animals. {01}

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether abciximab is distributed into breast milk. {01}

Pediatrics

No information is available on the relationship of age to the effects of abciximab in pediatric patients. Safety and efficacy have not been established. {01}


Geriatrics


Early clinical data suggested there may be an increased risk of major bleeding in patients over 65 years of age. {01} {02} However, overall bleeding rates were reduced in the CAPTURE trial, and were reduced further in the EPILOG trial with modified dosing regimens and specific patient management techniques {01} {10} {17}. Caution and attention to patient management are recommended.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Anticoagulants, oral {01}    (administration within 7 days of abciximab is not recommended unless the prothrombin time is £ 1.2 times control because of the increased risk of bleeding {01})


Anti-inflammatory drugs, nonsteroidal {01} or
Cefamandole or
Cefoperazone or
Cefotetan or
» Dipyridamole {01} or
» Platelet aggregation inhibitors {01} (see Appendix II) or
» Ticlopidine {01}    (concurrent use with abciximab may increase the risk of bleeding; caution is recommended during concurrent use)


» Dextran {01}    (concurrent or sequential use with abciximab may increase the risk of bleeding; concurrent use is not recommended)


» Heparin    (concurrent use with abciximab may increase the risk of bleeding)


» Thrombolytic agents    (concurrent use with abciximab may increase the risk of bleeding; caution is recommended during concurrent use{18})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Aneurysm, intracranial or
» Arteriovenous malformation, intracranial or
» Bleeding, active or
» Bleeding, gastrointestinal or genitourinary, recent (within 6 weeks) or
» Bleeding diathesis or
» Cerebrovascular accident (CVA), history of (within 2 years) or
» CVA with significant residual neurological deficit or
» Hypertension, severe, uncontrolled or
» Neoplasm, intracranial or
» Surgery, major, recent (within 6 weeks) or
» Thrombocytopenia (< 100,000 cells per microliter) or
» Trauma, major, recent (within 6 weeks) or
» Vasculitis, presumed or documented history of    (increased risk of bleeding with abciximab {01})


Risk-benefit should be considered when the following medical problems exist
» Age over 65 years or
» Gastrointestinal disease, history of or
» Weight < 75 kg    (increased risk of major bleeding with abciximab {01})


» Percutaneous coronary intervention, failed or
» Percutaneous coronary intervention, prolonged (lasting more than 70 minutes) or
» Percutaneous coronary intervention within 12 hours of the onset of symptoms of acute myocardial infarction    (increased risk of bleeding that may be additive to that of abciximab {01})


Hypersensitivity to abciximab or to murine proteins {01}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Activated clotting time (ACT)    (recommended at baseline prior to initiation of therapy,{18} during, and following therapy {14}; during percutaneous coronary intervention, the ACT should be maintained between 200 and 300 seconds; prior to arterial sheath removal, the ACT should be checked and should be £ 175 seconds before the sheath is removed {01})


» Activated partial thromboplastin time (APTT) and
» Prothrombin time (PT)    (recommended at baseline prior to initiation of abciximab therapy, during, and following therapy; when abciximab is initiated 18 to 24 hours before percutaneous coronary intervention, the APTT should be maintained between 60 and 85 seconds during the abciximab and heparin infusion period; if anticoagulation is continued following percutaneous coronary intervention, the APTT should be maintained between 60 and 85 seconds; prior to arterial sheath removal, the APTT should be checked and should be £ 50 seconds before the sheath is removed {01})


» Monitoring of potential bleeding sites    (careful attention to all potential bleeding sites, including catheter insertion sites, arterial and venous puncture sites, cutdown sites, needle puncture sites, and gastrointestinal, genitourinary, and retroperitoneal sites, is recommended {01})


» Platelet counts    (recommended at baseline prior to initiation of abciximab therapy, at 2 to 4 hours following the initial intravenous injection dose, and at 24 hours or prior to discharge, whichever is first. Additional platelet counts should be determined if a patient experiences an acute platelet decrease; if thrombocytopenia is verified, abciximab therapy should be discontinued immediately {01})




Side/Adverse Effects

Note: Human anti-chimeric antibody (HACA) development may occur secondary to abciximab therapy. {01} {13} In the EPIC, EPILOG, and CAPTURE trials, positive HACA responses occurred in approximately 5.8% of the abciximab-treated patients {01} {02} {10} {17}. There was no excess hypersensitivity or allergic reactions related to abciximab treatment compared to placebo treatment. {01} Patients who develop HACA titers may have allergic or hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies. {01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Bleeding {01} {02} {04} {11}
    
hypotension {01}

Note: Bleeding was the most common complication of abciximab therapy in the EPIC trial in which heparin was used in a non–weight-adjusted, standard-dose regimen {01} {02}. Approximately 70% of abciximab-treated patients with major bleeding (intracranial hemorrhage or a decrease in hemoglobin concentration by more than 5 grams per dL) had bleeding at the arterial access site in the groin. {01} {02} An increased incidence of major bleeding from retroperitoneal, gastrointestinal, genitourinary, and other sites also occurred in abciximab-treated patients. {01} {02}
Bleeding rates were reduced in the CAPTURE trial, and were reduced further in the EPILOG trial with modified dosing regimens and specific patient management techniques (see General Dosing Information ) {01} {10} {17}. In the EPILOG trial the incidence of major bleeding in patients treated with abciximab and low-dose, weight-adjusted heparin was not significantly different from that in patients receiving placebo {01} {10}.
If serious uncontrolled bleeding or the need for surgery occurs, abciximab should be discontinued. {01} If platelet function does not return to normal, it may be partly restored with platelet transfusions. {01}
Percutaneous coronary intervention within 12 hours of the onset of symptoms of acute myocardial infarction or prolonged or failed percutaneous coronary intervention may be associated in the angioplasty setting with an increased risk of bleeding that may be additive to that of abciximab. {01}
Hypotension is often related to bleeding complications associated with abciximab. {01}


Incidence less frequent
    
Thrombocytopenia {01} {02} {04}

Note: In the EPIC trial, thrombocytopenia (< 100,000 platelets per microliter) and severe thrombocytopenia (< 50,000 platelets per microliter) occurred in 5.2% and 1.6%, respectively, of patients receiving an initial intravenous injection plus infusion of abciximab. {04} The incidence of thrombocytopenia and requirement of platelet transfusions were lower in the subsequent CAPTURE and EPILOG trials {01}.


Incidence rare
    
Anemia {01}
    
bradycardia {01}
    
edema, peripheral {01}
    
leukocytosis {01}
    
pleural effusion or pleurisy {01}
    
pneumonia {01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Back Pain {18}
    
chest pain {18}
    
headache {18}

Incidence less frequent or rare
    
Abnormal thinking {18}
    
abnormal vision {01}
    
anxiety
    
confusion {01}
    
dizziness {18}
    
dyspepsia {18}( acid or sour stomach; belching; heartburn ; indigestion or stomach discomfort, upset, or pain)
    
hypesthesia {01}
    
nausea {01}
    
vomiting {01}





General Dosing Information
The abciximab preparation for the initial intravenous injection should be administered with a syringe equipped with a sterile, nonpyrogenic, low–protein-binding 0.2- or 0.22-micrometer syringe filter {01}. The abciximab preparation for continuous infusion should be filtered either upon its admixture using a sterile, nonpyrogenic, low–protein-binding 0.2- or 0.22-micrometer syringe filter, or upon its administration using an in-line, sterile, nonpyrogenic, low–protein-binding 0.2- or 0.22-micrometer filter {01}.

Abciximab administration may result in human anti-chimeric antibody (HACA) formation. {01} Therefore, readministration of abciximab may cause hypersensitivity reactions (including anaphylaxis), thrombocytopenia, or diminished benefit of abciximab. {01} However, there are no data evaluating readministration of abciximab to patients who have developed a positive HACA response after its initial administration. {01}

Hypersensitivity or anaphylaxis may occur at any time during abciximab administration. {01}

Patient management to reduce bleeding
   • Because of the risk of bleeding, arterial and venous punctures, intramuscular injections, and use of urinary catheters, nasotracheal tubes, nasogastric tubes, and automatic blood pressure cuffs should be minimized. {01} Noncompressible sites, such as subclavian or jugular veins, should be avoided when obtaining intravenous access. {01}
   • If serious uncontrolled bleeding or the need for surgery occurs, abciximab should be discontinued. {01} If platelet function does not return to normal, it may be partly restored with platelet transfusions. {01}
   • Since abciximab is associated with an increased bleeding rate, particularly at the site of arterial access for femoral sheath placement, care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger technique for obtaining sheath access. {01} Femoral vein sheath placement is not recommended, unless needed. {01} While the vascular sheath is in place, patients should be maintained on complete bed rest with the head of the bed placed at an angle of 30° or less and the affected limb kept in a straight position. {01} Patients may be medicated for back or groin pain as necessary. {01} Immediate discontinuation of heparin upon completion of the procedure and removal of the arterial sheath within 6 hours are strongly recommended, if the APTT is £ 50 seconds or the ACT is £ 175 seconds. {01} In all cases, heparin should be discontinued at least 2 hours prior to arterial sheath removal. {01} After the sheath is removed, pressure should be applied to the femoral artery for at least 30 minutes using either manual compression or a mechanical device for hemostasis. {01} A pressure dressing should be applied following hemostasis and the patient maintained on bed rest for 6 to 8 hours following sheath removal or discontinuation of abciximab therapy, or 4 hours after heparin is discontinued, whichever is later. {01} The pressure dressing should be removed prior to ambulation. {01}
   • The sheath insertion site and distal pulses of affected leg(s) should be checked frequently while the femoral artery sheath is in place and for 6 hours after the sheath is removed. {01} Any hematoma should be measured and monitored for enlargement. {01}
   • Careful attention to all potential bleeding sites, including catheter insertion sites, arterial and venous puncture sites, cutdown sites, needle puncture sites, and gastrointestinal, genitourinary, and retroperitoneal sites, is recommended. {01}

Heparin anticoagulation
Due to the high incidence of bleeding seen in the EPIC trial, the dosing regimens of concomitant heparin and the target levels for anticoagulation were successively varied in the CAPTURE and EPILOG trials. These modified dosing regimens, combined with other measures for patient management, were associated with reduced bleeding rates. For details of the anticoagulation regimens used in these trials, see the ReoPro package insert. {01}

For treatment of adverse effects


Recommended treatment consists of the following:


For anaphylaxis—
   • Stopping the infusion immediately. {01}
   • Symptomatic and supportive treatment. {01} Epinephrine, dopamine, theophylline, antihistamines, and corticosteroids should be readily available. {01}



For bleeding—
   • Stopping the infusion immediately. {01}
   • Symptomatic and supportive treatment. {01}




Parenteral Dosage Forms

ABCIXIMAB INJECTION

Usual adult dose
Prophylaxis of percutaneous coronary intervention–related thrombosis
   • In patients undergoing percutaneous coronary intervention:   —Initial: Intravenous, 250 mcg (0.25 mg) per kg of body weight administered as a bolus{18}{19}ten to sixty minutes prior to the start of percutaneous coronary intervention. {01} {02}
   —Maintenance: Intravenous infusion, 0.125 mcg per kg of body weight per minute (to a maximum of 10 mcg [0.01 mg] per minute) for twelve hours. {01}

   • In patients with unstable angina not responding to conventional medical therapy when percutaneous coronary intervention is planned within 24 hours:    —Initial: Intravenous, 250 mcg (0.25 mg) per kg of body weight as a bolus{18}. {01}
   —Maintenance: Intravenous infusion, 10 mcg (0.01 mg) per minute for eighteen to twenty-four hours, concluding one hour after the percutaneous coronary intervention. {01}


Note: Abciximab has been studied only with concomitant administration with heparin and aspirin. {01} {02} {14}
The continuous infusion of abciximab should be stopped in cases of failed percutaneous coronary intervention, since there is no evidence for the efficacy of abciximab in that setting. {01}
If serious bleeding that cannot be controlled by compression occurs, abciximab and heparin should be discontinued immediately. {01}



Usual pediatric dose
Safety and efficacy have not been established. {01}

Strength(s) usually available
U.S.—


2 mg per mL (single-use 5-mL vials) (Rx) [ReoPro®{18} (buffered solution of 0.01 molar sodium phosphate) (0.15 molar sodium chloride) (0.001% polysorbate 80 in Water for Injection)]

Canada—


2 mg per ml (single use 5 ml vials) (Rx) [ReoPro™ ( buffered solution of 0.01 molar sodium phosphate) ( 0.15 molar sodium chloride) (0.001% polysorbate 80)]

Note: No preservatives are added

{19}
Packaging and storage:
Store at 2 to 8 °C (36 to 46 °F). Protect from freezing.

Preparation of dosage form:
For the intravenous infusion solution, the necessary amount of abciximab should be added to an appropriate amount of 0.9% sodium chloride injection or 5% dextrose injection and infused at the calculated flow rate using a continuous infusion pump. {01}

Stability:
Discard any unused portion of the infusion solution. {01}

Incompatibilities:
Abciximab should be administered through a separate intravenous line. {01} No other medications should be added to the infusion solution. {01}

Auxiliary labeling:
   • Do not shake.



Developed: 07/05/1995
Revised: 10/10/2001



References
  1. ReoPro package insert (Lilly—US), Issued 12/94, Rec 2/95; Rev 11/97, Rec 11/97.
  1. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: 956-61.
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1995. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1994. p. 14.
  1. Faulds D, Sorkin EM. Abciximab (c7E3 Fab). A review of its pharmacology and therapeutic potential in ischemic heart disease. Drugs 1994; 48(4): 583-98.
  1. Topol EJ, Califf RM, Weisman HF, et al. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. Lancet 1994; 343: 881-6.
  1. Herrman JR, Hermans WR, Vos J, Serruys PW. Pharmacological approaches to the prevention of restenosis following angioplasty. The search for the holy grail? [Part I]. Drugs 1993; 46(1): 18-52.
  1. Kleinman NS, Ohman M, Califf RM, et al. Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the thrombolysis and angioplasty in myocardial infarction (TAMI) 8 pilot study. J Am Coll Cardiol 1993; 22(2): 381-9.
  1. Ellis SG, Bates ER, Schaible T, et al. Prospects for the use of antagonists to the platelet glycoprotein IIb/IIIa receptor to prevent postangioplasty restenosis and thrombosis. J Am Coll Cardiol 1991; 17: 89B-95B.
  1. Anderson HV, Kirkeeide RL, Krishnaswami A, et al. Cyclic flow variations after coronary angioplasty in humans: clinical and angiographic characteristics and elimination with 7E3 monoclonal antiplatelet antibody. J Am Coll Cardiol 1994; 23(5): 1031-7.
  1. The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689-96.
  1. Tcheng JE, Ellis SG, George BS, et al. Pharmacodynamics of chimeric glycoprotein IIb/IIIa intergrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation 1994; 90: 1757-64.
  1. Gold HK, Gimple LW, Yasuda T, et al. Pharmacodynamic study of F(ab") 2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris. J Clin Invest 1990; 86: 651-9.
  1. Ellis SG, Tcheng JE, Navetta FI, et al. Safety and antiplatelet effect of murine monoclonal antibody 7E3 Fab directed against platelet glycoprotein IIb/IIIa in patients undergoing elective coronary angioplasty. Coron Artery Dis 1993; 4(2): 167-75.
  1. Reviewer comment, 6/95.
  1. Panel comment, 6/95.
  1. Popma JJ, Satler LF. Early and late clinical outcome following coronary angioplasty performed with platelet glycoprotein IIb/IIIa receptor inhibition: the EPIC trial results. J Invasive Cardiol 1994; 6(suppl A): 19A-28A.
  1. The CAPTURE Investigators. Randomized placebo-controlled trial of abciximab before, during and after coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997; 349: 1429-35.
  1. Product Information: ReoPro®, abciximab. Eli Lilly, Indianapolis, In. (PI revised 05/2001) PI reviewed 9/2001.
  1. Product Information: ReoPro™, abciximab. Eli Lilly Canada Inc., Scarborough, Ontario (PI issued 10/2000) PI reviewed 9/2001
Hide
(web5)