Abciximab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

ReoPro: 2 mg/mL (5 mL [DSC]) [contains polysorbate 80]

Pharmacology

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

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 0.07 L/kg (Schror 2003)

Metabolism

Unbound abciximab metabolized via proteolytic cleavage (Schror 2003)

Onset of Action

Rapid; platelet aggregation reduced to <20% of baseline at 10 minutes

Time to Peak

Platelet inhibition: ~30 minutes (Mascelli 1998)

Duration of Action

Platelet function recovery: 24 to 48 hours (Tcheng 1994; Mascelli 1998); may be up to 72 hours for restoration of normal hemostasis (Schror 2003). Platelet function may remain abnormal for up to 7 days post infusion based on shear-dependent platelet function testing as opposed to platelet aggregometry (Osende 2001)

Half-Life Elimination

Plasma: ~30 minutes; dissociation half-life from GP IIb/IIIa receptors: up to 4 hours (Schror 2003). Note: 29% and 13% of abciximab estimated to remain on GP IIb/IIIa receptors at 8 and 15 days, respectively (Mascelli 1998)

Protein Binding

Mostly bound to GP IIb/IIIa receptors on platelet surface

Use: Labeled Indications

Percutaneous coronary intervention: Prevention of cardiac ischemic complications in patients undergoing percutaneous coronary intervention (PCI)

Unstable angina/non-ST-elevation myocardial infarction: Prevention of cardiac ischemic complications in patients with unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI) unresponsive to conventional therapy when PCI is scheduled within 24 hours

Note: Intended for use with aspirin and heparin, at a minimum. Safety and efficacy of abciximab use in patients not undergoing PCI have not been established.

Guideline recommendations:

NSTEMI: In patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) treated with an early invasive strategy and dual antiplatelet therapy with intermediate/high-risk features (eg, positive troponin), the preferred GP IIb/IIIa inhibitors that may be considered as part of initial antiplatelet therapy are eptifibatide or tirofiban (ACC/AHA [Amsterdam 2014]).

Use: Off Label

ST-elevation myocardial infarction (STEMI) undergoing primary PCIbyes

Data from a double-blind, placebo controlled trial in patients with STEMI undergoing primary PCI demonstrated that the use of abciximab in this setting reduces the incidence of the primary outcome of death, reinfarction, or urgent target vessel revascularization Montalescot 2001. Additional data from a randomized study with a 2x2 factorial design demonstrated that abciximab may be used to support primary PCI (ie, PTCA or stent) in patients with STEMI Stone 2002. Additional trials may be necessary to further define the role of abciximab in this setting.

Based on the 2013 American College of Cardiology/American Heart Association (ACCF/AHA) guidelines for the management of ST-elevation myocardial infarction (STEMI), abciximab may be administered at the time of primary PCI in select patients with STEMI in combination with heparin or bivalirudin. Adjunctive use of abciximab may be helpful at the time of PCI in patients with large clot burden or inadequate P2Y12 loading.

Intracoronary (off-label route): Mixed data exists on the administration of abciximab via the intracoronary route. In a randomized, open-label, 2x2 factorial designed study, patients with large anterior STEMI who were administered intracoronary abciximab to the infarct lesion site, demonstrated a significant reduction in infarct size whereas manual aspiration thrombectomy did not demonstrate a reduction Stone 2012. In another randomized, open-label, multicenter trial, abciximab did not reduce the composite endpoint (death, reinfarction, or congestive heart failure) in all patients with STEMI; however, patients who received intracoronary abciximab had lower rates of congestive heart failure Thiele 2012. The ACCF/AHA guidelines for the management of STEMI, state that it may be reasonable to administer intracoronary abciximab to select patients with STEMI undergoing primary PCI ACCF/AHA [O'Gara 2013].

Contraindications

Hypersensitivity to abciximab, 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 with significant residual neurological deficit; bleeding diathesis; administration of oral anticoagulants within 7 days unless prothrombin time (PT) is ≤1.2 times control PT value; thrombocytopenia (<100,000 cells/mcL); recent (within 6 weeks) major surgery or trauma; intracranial tumor, arteriovenous malformation, or aneurysm; severe uncontrolled hypertension; history of vasculitis (presumed or documented); use of dextran before PCI or intent to use dextran during PCI.

Dosage and Administration

Dosing: Adult

Note: Reopro is no longer available in the US.

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

Unstable angina/non-ST-elevation MI (UA/NSTEMI) unresponsive to conventional medical therapy with planned PCI within 24 hours: IV: 0.25 mg/kg bolus followed by an 18- to 24-hour infusion of 10 mcg/minute, concluding 1 hour after PCI.

ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) (off-label use) (ACCF/AHA [O'Gara 2013]):

IV:

Loading dose: 0.25 mg/kg bolus administered at the time of PCI.

Maintenance infusion: 0.125 mcg/kg/minute (maximum: 10 mcg/minute) continued for up to 12 hours.

Intracoronary (off-label route): 0.25 mg/kg bolus administered directly to the site of the infarct lesion; may be followed with an intravenous maintenance infusion if refractory intraprocedural thrombotic complications occur (Stone 2012).

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

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

Continuous infusion: Withdraw required amount of abciximab into a syringe using a 0.2 or 5 micron low protein-binding syringe filter (or equivalent) and inject into an appropriate container of NS or D5W. If a syringe filter was not used to prepare the infusion, administer using an in-line 0.2 or 0.22 micron low protein-binding filter.

Note: 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 to 24 hours via pump after bolus dose; length of therapy dependent on indication. Some institutions use a standard concentration of 9 mg in 250 mL of D5W or NS.

Administration

For IV administration. Solution must be filtered using a 0.2 or 5 micron low protein-binding syringe filter during preparation or via a 0.2 to 0.22 micron low protein-binding inline filter during administration. Do not shake vial.

Intracoronary administration (off-label route): In select STEMI cases (eg, anterior STEMI), abciximab bolus may be administered through the guiding catheter directly to the culprit lesion site (Stone 2012; Thiele 2012)

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. After admixture in NS or D5W, the prepared solution is stable for 12 hours. Discard any unused portion.

The following stability information has also been reported: May store intact vials at 24°C to 28°C (76°F to 82°F) for up to 8 days (data on file [Eli Lilly, 2011]). However, the manufacturer recommends storage under refrigeration. Room temperature stability information should only be utilized in situations where the drug has been inadvertently exposed to prolonged room temperature.

Drug Interactions

Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Consider therapy modification

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

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

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Consider therapy modification

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. Consider therapy modification

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

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

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

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

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

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

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 & oncologic: Minor hemorrhage (4% to 17%), major hemorrhage (1% to 14%)

Neuromuscular & skeletal: Back pain (18%)

Miscellaneous: Antibody development (HACA, first exposure: 6%; readministration: 27%; four or more exposures: 44%)

1% to 10%:

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

Gastrointestinal: Abdominal pain (3%)

Hematologic & oncologic: Thrombocytopenia: <100,000 cells/mm³ (3% to 6%); <50,000 cells/mm³ (0.4% to 2%)

Local: Pain at injection site (4%)

<1%: Abdominal distension, abnormality in thinking, abscess, agitation, allergic reaction (possible), anaphylaxis (possible), anemia, anxiety, arteriovenous fistula, bladder pain, bronchitis, bronchospasm, bullous skin disease, cellulitis, cerebrovascular accident, cold extremities, coma, complete atrioventricular block, confusion, diabetes mellitus, diaphoresis, diarrhea, diplopia, dizziness, dyspepsia, dysuria, edema, embolism, gastroesophageal reflux disease, hyperkalemia, hypertonia, hypoesthesia, incisional pain, incomplete atrioventricular block, inflammation, intestinal obstruction, intracranial hemorrhage, leukocytosis, muscle spasm, myalgia, nodal arrhythmia, pain, pallor, palpitations, petechiae, pleural effusion, pleurisy, pneumonia, prostatitis, pruritus, pseudoaneurysm, pulmonary alveolar hemorrhage, pulmonary embolism, rales, renal insufficiency, rhonchi, thrombophlebitis, urinary frequency, urinary incontinence, urinary retention, ventricular tachycardia, visual disturbance, weakness, wound, xerostomia

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 [rare], sometimes fatal).
• Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; monitor closely for bleeding, especially the arterial access site for the cardiac catheterization. Use with extreme caution in patients with platelet counts <150,000/mm³, hemorrhagic retinopathy, previous history of GI disease, recent thrombolytic therapy and in chronic dialysis patients. Use caution with administration of other drugs affecting hemostasis. Minimize other procedures, including arterial and venous punctures, IM injections, use of urinary catheters, nasogastric tubes, and automatic blood pressure cuffs. Increased risk of hemorrhage during or following angioplasty is associated with unsuccessful percutaneous coronary intervention (PCI), PCI procedure >70 minutes duration, or PCI performed within 12 hours of symptom onset for acute myocardial infarction. When attempting IV access, avoid noncompressible sites (eg, subclavian or jugular veins). If serious uncontrolled bleeding or the need for emergency surgery arises, discontinue abciximab.
• Thrombocytopenia: Thrombocytopenia, including severe cases, have been reported. Most severe cases occurred within 24 hours, with some cases occurring up to 2 weeks after administration. Readministration within 30 days or in patients with human antichimeric antibodies at baseline increases the incidence and severity of thrombocytopenia. A history of thrombocytopenia with prior abciximab use increases the risk of recurrence. Monitor platelets at baseline, during, and after treatment and as clinically indicated; immediately discontinue if thrombocytopenia occurs.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in patients >65 years of age; may have increased risk of bleeding.
• Low weight patients: Use with caution in patients weighing <75 kg; may have increased risk of bleeding.

Other warnings/precautions:

• Diminished efficacy: Administration may result in human antichimeric antibody formation that can cause diminished efficacy upon readministration.
• Sheath removal: Discontinuation of heparin immediately upon completion of the procedure and removal of the sheath within 6 hours is strongly recommended as long as ACT <150 to 180 seconds or aPTT <50 seconds (ACCF/AHA/SCAI [Levine 2011]). Use standard compression techniques after sheath removal. Monitor the site closely afterwards for further bleeding.
• Surgery: Discontinue ≥12 hours prior to coronary artery bypass graft surgery (ACC/AHA [Amsterdam 2014]).

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 to 4 hours following bolus infusion, at 24 hours (or prior to discharge, if before 24 hours), and as clinically indicated. To minimize risk of bleeding:

Abciximab initiated 18 to 24 hours prior to percutaneous coronary intervention (PCI): Maintain aPTT between 60 to 85 seconds during the heparin/abciximab infusion period

During PCI: Maintain ACT between 200 to 300 seconds

Following PCI (if anticoagulation is maintained): Maintain aPTT between 50 to 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 if femoral access utilized for percutaneous coronary intervention. 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 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; examine urine, stool, and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.

Pregnancy

Pregnancy Considerations

In vitro studies have shown only small amounts of abciximab to cross the placenta (Miller 2003). Information related to the use of abciximab in pregnancy is limited (Santiago-Diaz 2009; Sebastian 1998).

Patient Education

What is this drug used for?

• It is used during a heart treatment to protect the arteries.
• It is used to lower the number of heart attacks in patients who have unstable angina or mild heart attacks.

Frequently reported side effects of this drug

• Back pain
• Nausea
• Vomiting

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding
• Severe headache
• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes
• Severe dizziness
• Passing out
• Chest pain
• Fall or crash hitting head
• Severe loss of strength and energy
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.