Abciximab

U.S. BRAND NAMES — ReoPro®

PHARMACOLOGIC CATEGORY
Antiplatelet Agent, Glycoprotein IIb/IIIa Inhibitor

DOSING: ADULTS
Percutaneous coronary intervention (PCI): I.V.: 0.25 mg/kg bolus administered 10-60 minutes prior to start of PCI followed by an infusion of 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours

Patients with unstable angina not responding to conventional medical therapy with planned PCI within 24 hours: I.V.: 0.25 mg/kg bolus followed by an 18- to 24-hour infusion of 10 mcg/minute, concluding 1 hour after PCI.

ST-elevation MI combination regimen (unlabeled): Half-dose tenecteplase (15-25 mg based on weight), abciximab 0.25 mg/kg bolus then 0.125 mcg/kg/minute (maximum: 10 mcg/minute) for 12 hours and heparin dosing as follows: Concurrent bolus of 40 units/kg (maximum: 3000 units), then 7 units/kg/hour (maximum: 800 units/hour) as continuous infusion. Adjust to aPTT target of 50-70 seconds.

DOSING: ELDERLY — Refer to adult dosing.

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

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

DOSAGE FORMS: CONCISE
Injection, solution:
ReoPro®: 2 mg/mL (5 mL)

GENERIC EQUIVALENT AVAILABLE — No

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). Solution must be filtered prior to administration. Do not shake the vial.

Bolus dose: Aseptically withdraw the necessary amount of abciximab for the bolus dose into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent); the bolus should be administered 10-60 minutes before the procedure.

Continuous infusion: Aseptically withdraw amount required of abciximab for the infusion through a 0.2 or 5 micron low protein-binding syringe filter into a syringe; inject this into 250 mL of NS or D5W to make solution. If a syringe filter was not used when preparing the infusion, administer using an in-line 0.2 or 0.22 micron low protein-binding filter. Note: Alternatively, a standard concentration of 7.2 mg in 250 mL of NS or D5W may also be prepared for all patients and administered at the standard dose (0.125 mcg/kg/minute; maximum: 10 mcg/minute) with a variable rate in mL/hour. Infuse for 12-24 hours via pump after bolus dose; length of therapy dependent on indication.

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

USE — Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI); prevention of cardiac ischemic complications in patients with unstable angina not responding to conventional therapy when PCI is scheduled within 24 hours

Note: Intended for use with aspirin and heparin, at a minimum.

USE - UNLABELED / INVESTIGATIONAL — ST-elevation MI: Combination regimen of abciximab (full dose), tenecteplase (half dose), and heparin (unlabeled dose)

ADVERSE REACTIONS SIGNIFICANT — 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 (14.4%), chest pain (11.4%)
Gastrointestinal: Nausea (13.6%)
Hematologic: Minor bleeding (4.0% to 16.8%)
Neuromuscular & skeletal: Back pain (17.6%)

1% to 10%:
Cardiovascular: Bradycardia (4.5%), peripheral edema (1.6%)
Central nervous system: Headache (6.45)
Gastrointestinal: Vomiting (7.3%), abdominal pain (3.1%)
Hematologic: Major bleeding (1.1% to 14%), thrombocytopenia: <100,000 cells/mm3 (2.5% to 5.6%); <50,000 cells/mm3 (0.4% to 1.7%)
Local: Injection site pain (3.6%)

<1% (Limited to important or life-threatening): Abnormal thinking, allergic reactions/anaphylaxis (possible), AV block, bronchospasm, bullous eruption, coma, confusion, diabetes mellitus, embolism, hyperkalemia, ileus, inflammation, intracranial hemorrhage, myalgia, nodal arrhythmia, pleural effusion, pulmonary embolism, prostatitis, pruritus, stroke, urinary retention, ventricular tachycardia, xerostomia

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/µL); 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
Concerns related to adverse effects: Anaphylaxis/hypersensitivity reactions: Administration may result in human antichimeric antibody formation that can cause hypersensitivity reactions (including anaphylaxis). Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm3,>70 minutes duration, or PTCA performed within 12 hours of symptom onset for acute myocardial infarction. Thrombocytopenia: Administration may result in human antichimeric antibody formation that can cause thrombocytopenia; readministration within 30 days or in patients with human antichimeric antibodies (HACA) increases the incidence and severity of thrombocytopenia.

Special populations: Elderly: Use with caution in patients >65 years of age; increased risk of bleeding. Low weight patients: Use with caution in patients weighing <75 kg; increased risk of bleeding. Pediatrics: Safety and efficacy have not been established in children.

Other warnings/precautions: Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy. Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT ≤ 175 seconds or aPTT ≤ 50 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.

DRUG INTERACTIONS
Anticoagulants: Antiplatelet Agents may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Antiplatelet Agents: May enhance the anticoagulant effect of other Antiplatelet Agents. Risk C: Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Antiplatelet Agents. Risk C: Monitor therapy

Dextran: May enhance the anticoagulant effect of Abciximab. Risk X: Avoid combination

Drotrecogin Alfa: Antiplatelet Agents may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Risk D: Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Antiplatelet Agents. Bleeding may occur. Risk D: Consider therapy modification

Ibritumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Monoclonal Antibodies: Abciximab may enhance the potential for allergic or hypersensitivity reactions to Monoclonal Antibodies. Also may cause thrombocytopenia or diminished therapeutic effects. Exceptions: Alefacept. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of Antiplatelet Agents. An increased risk of bleeding may occur. Nonsteroidal Anti-Inflammatory Agents may diminish the cardioprotective effect of Antiplatelet Agents. This interaction is likely specific to aspirin, and not to other antiplatelet agents. Risk C: Monitor therapy

Omega-3-Acid Ethyl Esters: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Antiplatelet Agents. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy

Salicylates: Antiplatelet Agents may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Thrombolytic Agents: Antiplatelet Agents may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Antiplatelet Agents may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Risk C: Monitor therapy

PREGNANCY RISK FACTOR — C (show table)

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

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 bedrest with the head of the bed at a 30º 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.

CANADIAN BRAND NAMES — ReoPro®

INTERNATIONAL BRAND NAMES — ReoPro (AR, AT, AU, BE, BR, CH, CN, CZ, DE, DK, ES, FI, FR, GB, GR, IE, IN, IT, KP, LU, MX, MY, NL, NO, PE, PK, PL, PT, SE, SG, TH, TW, ZA)

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