Abciximab

Pronunciation

 (ab SIK si mab)

U.S. Brand Names

 ReoPro

Synonyms

 C7E3; 7E3

Generic Available

 No

Canadian Brand Names

 Reopro

Use

 Prevention of acute cardiac ischemic complications in patients at high risk for abrupt closure of the treated coronary vessel and patients at risk of restenosis; an adjunct with heparin to prevent cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when a percutaneous coronary intervention is scheduled within 24 hours

Pregnancy Risk Factor

 C

Pregnancy Implications

 Animal reproduction studies have not been conducted. In vitro studies have shown only small amounts of abciximab to cross the placenta. It is not known whether abciximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity

Lactation

 Excretion in breast milk unknown/use caution

Contraindications

 Hypersensitivity to abciximab, to murine proteins, or any component of the formulation; active internal hemorrhage or recent (within 6 weeks) clinically significant GI or GU bleeding; history of cerebrovascular accident within 2 years or cerebrovascular accident with significant neurological deficit; clotting abnormalities or administration of oral anticoagulants within 7 days unless prothrombin time (PT) is 1.2 times control PT value; thrombocytopenia (<100,000 cells/L); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis; use of dextran before PTCA or intent to use dextran during PTCA; concomitant use of another parenteral GP IIb/IIIa inhibitor

Warnings/Precautions

 Administration of abciximab is associated with increased frequency of major bleeding complications, including retroperitoneal bleeding, pulmonary bleeding, spontaneous GI or GU bleeding, and bleeding at the arterial access. Risk may be increased in the following: Patients weighing <75 kilograms, elderly patients (>65 years of age), history of previous GI disease, recent thrombolytic therapy. Avoid the creation of venous access at noncompressible sites.

The risk of major bleeds may increase with concurrent use of thrombolytics. Anticoagulation, such as with heparin, may contribute to the risk of bleeding. In serious, uncontrolled bleeding, abciximab and heparin should be stopped. Increased risk of hemorrhage during or following angioplasty is associated with unsuccessful PTCA, PTCA procedure >70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction.

Administration of abciximab may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis), thrombocytopenia, or diminished efficacy. Readministration of abciximab within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.

Adverse Reactions

 As with all drugs which may affect hemostasis, bleeding is associated with abciximab. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.

>10%:

Cardiovascular: Hypotension (14%), chest pain (11%)

Gastrointestinal: Nausea (14%)

Hematologic: Minor bleeding (4% to 17%)

Neuromuscular & skeletal: Back pain (18%)

1% to 10%:

Cardiovascular: Bradycardia (5%), peripheral edema (2%)

Central nervous system: Headache (7%)

Gastrointestinal: Vomiting (7%), abdominal pain (3%)

Hematologic: Major bleeding (1% to 14%), thrombocytopenia: <100,000 cells/mm3 (3% to 6%); <50,000 cells/mm3 (0.4% to 2%)

Local: Injection site pain (4%)

<1% (Limited to important or life-threatening): Stroke, intracranial hemorrhage, ventricular tachycardia, pseudoaneurysm, palpitation, arteriovenous fistula, incomplete AV block, nodal arrhythmia, complete AV block, embolism, thrombophlebitis, dyspepsia, diarrhea, ileus, gastroesophageal reflux, anemia, leukocytosis, petechiae, dizziness, agitation, anxiety, abnormal thinking, hypesthesia, confusion, muscle contractions, coma, hypertonia, diplopia, pneumonia, pleural effusion, bronchitis, bronchospasm, pulmonary embolism, myalgia, urinary retention, dysuria, urinary incontinence, cystalgia, prostatitis, pain, diaphoresis increased, weakness, pruritus, abnormal vision, cellulitis, peripheral coldness, xerostomia, hyperkalemia, diabetes mellitus, bullous eruption, inflammation, allergic reactions/anaphylaxis (possible)

Overdosage/Toxicology

 Since abciximab is a platelet antiaggregate, patients who bleed following administration may be best treated with platelet infusions.

Drug Interactions

Heparin and aspirin: Use with aspirin and heparin may increase bleeding over aspirin and heparin alone. However, aspirin and heparin were used concurrently in the majority of patients in the major clinical studies of abciximab.

Monoclonal antibodies: Allergic reactions may be increased in patients who have received diagnostic or therapeutic monoclonal antibodies due to the presence of HACA antibodies.

Thrombolytic agents theoretically may increase the risk of bleeding; use with caution.

Warfarin and oral anticoagulants: Risk of bleeding may be increased during concurrent therapy.

Other IIb/IIIa antagonists: Avoid concomitant use of other glycoprotein IIb/IIIa antagonists (see Contraindications).

Stability

 Vials should be stored at 2C to 8C, do not freeze; after admixture, the prepared solution is stable for 12 hours; abciximab should be administered in a separate intravenous line; no incompatibilities have been observed with glass bottles or PVC bags

Compatibility

 Abciximab should be administered in a separate intravenous line. No incompatibilities have been observed with glass bottles or PVC bags.

Mechanism of Action

 Fab antibody fragment of the chimeric human-murine monoclonal antibody 7E3; this agent binds to platelet IIb/IIIa receptors, resulting in steric hindrance, thus inhibiting platelet aggregation

Pharmacodynamics/Kinetics

 Half-life elimination: ~30 minutes

Dosage

 I.V.: 0.25 mg/kg bolus administered 10-60 minutes before the start of intervention followed by an infusion of 0.125 mcg/kg/minute (to a maximum of 10 mcg/minute) for 12 hours

Patients with unstable angina not responding to conventional medical therapy and who are planning to undergo percutaneous coronary intervention within 24 hours may be treated with abciximab 0.25 mg/kg intravenous bolus followed by an 18- to 24-hour intravenous infusion of 10 mcg/minute, concluding 1 hour after the percutaneous coronary intervention.

Administration

 Abciximab is intended for coadministration with aspirin postangioplasty and heparin infused and weight adjusted to maintain a therapeutic bleeding time (eg, ACT 300-500 seconds)

Bolus dose: Do not shake the vial. Aseptically withdraw the necessary amount of abciximab (2 mg/mL) for the bolus dose through a 0.22-micron filter into a syringe; the bolus should be administered 10-60 minutes before the procedure

Continuous infusion: Aseptically withdraw 4.5 mL (9 mg) of abciximab for the infusion through a 0.22 micron filter into a syringe; inject this into 250 mL of NS or D5W to make a solution with a final concentration of 35 mcg/mL. Infuse at a rate of 17 mL/hour (10 mcg/minute) for 12 hours via pump; filter all infusions.

Monitoring Parameters

 Prothrombin time, activated partial thromboplastin time (aPTT), hemoglobin, hematocrit, platelet count, fibrinogen, fibrin split products, transfusion requirements, signs of hypersensitivity reactions, guaiac stools, Hemastix urine. Platelet count should be monitored at baseline, 2-4 hours following bolus infusion, and at 24 hours (or prior to discharge, if before 24 hours). To minimize risk of bleeding:

Abciximab initiated 18-24 hours prior to PCI: Maintain aPTT between 60-85 seconds during the heparin/abciximab infusion period

During PCI: Maintain ACT between 200-300 seconds

Following PCI (if anticoagulation is maintained): Maintain aPTT between 50-75 seconds

Sheath removal should not occur until aPTT is 50 seconds or ACT 175 seconds.

Maintain bleeding precautions, avoid unnecessary arterial and venous punctures, use saline or heparin lock for blood drawing, assess sheath insertion site and distal pulses of affected leg every 15 minutes for the first hour and then every 1 hour for the next 6 hours. Arterial access site care is important to prevent bleeding. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Femoral vein sheath placement should be avoided unless needed. While the vascular sheath is in place, patients should be maintained on complete bed rest with the head of the bed at a 30 angle and the affected limb restrained in a straight position.

Observe patient for mental status changes, hemorrhage, assess nose and mouth mucous membranes, puncture sites for oozing, ecchymosis and hematoma formation, and examine urine, stool and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.

Patient Education

 This medication can only be administered I.V. You will have a tendency to bleed easily following this medication; use caution to prevent injury (use electric razor, soft toothbrush, and use caution with knives, needles, or anything sharp). If bleeding occurs, apply pressure to bleeding spot until bleeding stops completely. Report unusual bruising or bleeding; blood in urine, stool, or vomitus; bleeding gums; or vision changes. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Anesthesia and Critical Care Concerns/Other Considerations

 Platelet Effects: Abciximab has a long duration of action and platelet effects reverse slowly. It can take 24-48 hours for platelet function to return to normal after discontinuation of infusion making it difficult to use in patients likely to need CABG. Antiplatelet effects can be reversed with platelet transfusions. Platelet count monitoring is recommended 2-4 hours after initiation, and at 24 hours or prior to discharge, whichever is first. Acute profound thrombocytopenia with abciximab occurs within 24 hours of administration and may be treated by discontinuing the infusion (if still running) and administering platelets. Platelet counts should recover rapidly after discontinuation.

Cardiovascular Considerations

Acute Coronary Syndrome(ACS): The 2002 ACC/AHA guidelines for unstable angina/non-ST-segment elevation myocardial infarctions (UA/NSTEMI) recommend administration of intravenous glycoprotein llb/llla inhibitors (along with ASA and heparin) in patients with non-ST-segment elevation ACS who are expected to undergo catheterization and PCI. In such patients in which PCI in not expected, eptifibatide or tirofiban should be administered (along with ASA and either heparin or LMWH) if high-risk features (eg, positive biochemical markers of infarction, ST-segment depression, sustained VT, >75 years of age, or signs of LV dysfunction) or refractory ischemia are present.

Percutaneous Coronary Intervention (PCI): A glycoprotein llb/llla inhibitor is recommended for patients who will undergo PCI, especially those with unstable angina or other high risks for postprocedure ischemic complications. In the TARGET trial, abciximab (FDA-approved dose) and tirofiban (10 mcg/kg bolus; infusion of 0.15 mcg/kg/minute for 18-24 hours) were compared to each other in patients undergoing coronary stenting. The primary endpoint was death, nonfatal MI, or urgent target vessel revascularization at 30 days. Abciximab improved outcome to a greater extent than tirofiban did primarily by reducing nonfatal MI. Follow-up at 6 months revealed no significant difference in primary outcomes between treatments, but a trend existed in favor of abciximab reducing the occurrence of MIs.

Adjunct to Thrombolysis: In the GUSTO V trial, patients with acute MI were randomized to standard-dose reteplase or half-dose reteplase (two boluses of 5 units each, 30 minutes apart) and full dose abciximab. Mortality at 30 days (primary endpoint) was similar in both groups. The combination treatment group had significantly fewer reinfarctions or recurrent episodes of ischemia. Combination treatment was also associated with less need for urgent revascularization. More bleeding occurred in the combination treatment group, but the incidence of nonfatal disabling stroke and stroke of any type were similar in both groups. Overall, no difference in intracranial hemorrhages was observed between the two treatments, but a trend towards an increased incidence occurred in patients >75 years of age who received combination treatment. Patients with acute MI were randomized in an open-label study to full-dose tenecteplase and enoxaparin, half-dose tenecteplase with weight-based heparin and a 12-hour infusion of abciximab or full-dose tenecteplase with weight-based heparin. The primary endpoint (30 days) was mortality, in-house reinfarction, and in-house refractory ischemia. The abciximab arm had significantly less mortality, reinfarction, and refractory ischemia than in the unfractionated heparin/full-dose tenecteplase. The 2004 ACC/AHA guidelines for STEMI recommend that pharmacologic reperfusion with abciximab and half-dose reteplase or tenecteplase may be considered in patients <75 years of age with anterior wall infarctions and no risk factors for bleeding.

Platelet Effects: Abciximab has a long duration of action and platelet effects reverse slowly. It can take 24-48 hours for platelet function to return to normal after discontinuation of infusion making it difficult to use in patients likely to need CABG. Antiplatelet effects can be reversed with platelet transfusions. Platelet count monitoring is recommended 2-4 hours after initiation. and at 24 hours or prior to discharge, whichever is first. Acute profound thrombocytopenia with abciximab occurs within 24 hours of administration and may be treated by discontinuing the infusion (if still running) and administering platelets. Platelet counts should recover rapidly after discontinuation.

Dental Health: Effects on Dental Treatment

 Key adverse event(s) related to dental treatment: As with all anticoagulants, bleeding is a potential adverse effect of abciximab during dental surgery; risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility. Medical consult is suggested. It is unlikely that ambulatory patients presenting for dental treatment will be taking intravenous anticoagulant therapy.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions

Mental Health: Effects on Mental Status

 None reported

Mental Health: Effects on Psychiatric Treatment

 None reported

Dosage Forms

 Injection, solution: 2 mg/mL (5 mL)

References

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.

Aguirre FV, Topol EJ, and Ferguson JJ, "Bleeding Complications With the Chimeric Antibody to Platelet Glycoprotein IIb/IIIa Intergrin in Patients Undergoing Percutaneous Coronary Intervention. EPIC Investigators,"Circulation, 1995, 91(12):2882-90.

Antman EM, Giugliano RP, Gibson CM, et al, "Abciximab Facilitates the Rate and Extent of Thrombolysis: Results of the Thrombolysis in Myocardial Infarction (TIMI) 14 Trial. The TIMI 14 Investigators,"Circulation, 1999, 99(21):2720-32.

"ASSENT-3 Investigators. Efficacy and Safety of Tenecteplase in Combination With Enoxaparin, Abciximab, or Unfractionated Heparin: The ASSENT-3 Randomised Trial in Acute Myocardial Infarction,"Lancet, 2001, 358 (9282):605-13.

Berkowitz SD, Harrington RA, Rund MM, et al, "Acute Profound Thrombocytopenia After C7E3 Fab (Abciximab) Therapy,"Circulation, 1997, 95(4):809-13.

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA 2002 Guideline Update for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction - Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),"J Am Coll Cardiol, 2002, 40(7):1366-74. Available at: http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm. Accessed May 20, 2003.

Brener SJ, Barr LA, Burchenal JE, et al, "Randomized, Placebo-Controlled Trial of Platelet Glycoprotein IIb/IIIa Blockade With Primary Angioplasty for Acute Myocardial Infarction," ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators, Circulation, 1998, 98(8):734-41.

Hamm CW, Heeschen C, Goldmann B, et al, "Benefit of Abciximab in Patients With Refractory Unstable Angina in Relation to Serum Troponin T Levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators,"N Engl J Med, 1999, 340(21):1623-9.

Lincoff AM, Califf RM, Anderson KM, et al, "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. EPIC Investigators. Evaluation of 7E3 in Preventing Ischemic Complications,"J Am Coll Cardiol, 1997, 30(1):149-56.

Lincoff AM, Califf RM, Van de Werf F, et al, "Mortality at 1 Year With Combination Platelet Glycoprotein IIb/IIIa Inhibition and Reduced-Dose Fibrinolytic Therapy vs Conventional Fibrinolytic Therapy for Acute Myocardial Infarction: GUSTO V Randomized Trial,"JAMA, 2002, 288(17):2130-5.

Lincoff AM, Califf RM, Moliterno DJ, et al, "Complementary Clinical Benefits of Coronary-Artery Stenting and Blockade of Platelet Glycoprotein IIb/IIIa Receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators,"N Engl J Med, 1999, 341(5):319-27.

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"Platelet Glycoprotein IIb/IIIa Receptor Blockade and Low-Dose Heparin During Percutaneous Coronary Revascularization. The EPILOG Investigators,"N Engl J Med, 1997, 336(24):1689-96.

"Randomised Placebo-Controlled Trial of Abciximab Before and During Coronary Intervention in Refractory Unstable Angina: The CAPTURE Study,"Lancet, 1997, 349(9063):1429-35.

Smith SC Jr, Dove JT, Jacobs AK, et al, "ACC/AHA Guidelines of Percutaneous Coronary Interventions (Revision of the 1993 PTCA Guidelines) - Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty),"J Am Coll Cardiol, 2001, 37(8):2215-39.

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International Brand Names

 ReoPro (AR, AT, AU, BE, BR, CA, CH, CL, CZ, DE, DK, ES, FI, FR, GB, IE, IL, IN, IT, LU, NL, NO, NZ, PL, RO, RU, SE, SG, TH, YU, ZA)

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