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ReoPro

Generic Name: Abciximab
Class: Platelet-Aggregation Inhibitors
Chemical Name: Human mouse monoclonal c7E3 clone p7E3VHhCgamma4 Fab fragment anti-human glycoprotein IIb/IIIa receptor immunoglobulin G disulfide with human-mouse monoclonal c7E3 clone p7E3vkhCk light chain
CAS Number: 143653-53-6

Introduction

Platelet aggregation inhibitor; a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor.1 2 4 5

Uses for ReoPro

Acute Ischemic Complications of PCI

Adjunct to anticoagulant therapy (e.g., heparin [referring throughout this monograph to unfractionated heparin], low molecular weight heparin), aspirin, and/or clopidogrel to prevent acute cardiac ischemic complications in patients undergoing PCI or in patients with non-ST-segment-elevation acute coronary syndromes (i.e., unstable angina or non-ST-segment-elevation MI [NSTEMI]) not responding to conventional medical therapy in whom PCI is planned within 24 hours.1 2 4 5 7 10 11 71 91 994

Adjunctive therapy with a GP IIb/IIIa-receptor inhibitor can reduce the incidence of cardiac ischemic events, including subsequent MI and death, in patients with non-ST-segment-elevation acute coronary syndromes undergoing PCI and in patients without these conditions undergoing PCI.10 11 17 47 48 49 50 51

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Safety and efficacy in patients not undergoing PCI not established.1 1016

The American College of Cardiology Foundation (ACCF), AHA, the Society for Cardiovascular Angiography and Interventions (SCAI), and other experts currently do not recommend routine use of GP IIb/IIIa-receptor inhibitors in patients with ST-segment elevation MI (STEMI) undergoing PCI; however, selective use of these drugs as an adjunct to heparin may be reasonable in certain high-risk patients (e.g., those with large anterior MI and/or large thrombus).994 1016

ACCF/AHA/SCAI state that administration of a GP IIb/IIIa-receptor inhibitor at the time of PCI as an adjunct to heparin may be particularly useful in patients with unstable angina/NSTEMI who have high-risk features (e.g., elevated troponin) and are not receiving bivalirudin and are not adequately pretreated with clopidogrel.994

Regarding choice of GP IIb/IIIa-receptor inhibitor in patients undergoing PCI, IV abciximab, “double-bolus” IV eptifibatide, and high-dose tirofiban given by direct IV injection all produce a high degree of platelet inhibition and reduce ischemic complications.994

Unstable Angina and NSTEMI

Has been used in patients with unstable angina or NSTEMI managed with conservative medical therapy only; however, manufacturer and some clinicians state that safety and efficacy of abciximab not established in such patients who are not undergoing PCI.1 991

A GP IIb/IIIa-receptor inhibitor may be used in conjunction with aspirin prior to diagnostic angiography (“upstream”) in patients with unstable angina or NSTEMI in whom an initial invasive management strategy is planned; however, IV eptifibatide or tirofiban is the preferred GP IIb/IIIa inhibitor for this use.991 Abciximab is recommended in this situation only if there is no appreciable delay before angiography and PCI is likely to be performed.991

Adjunctive Therapy during Thrombolysis to Prevent Reocclusion

Has been used concomitantly with a thrombolytic agent (e.g., reteplase, tenecteplase) and IV heparin to prevent coronary artery reocclusion after an acute MI.97 1016 Some clinicians state that combined therapy with abciximab and a thrombolytic agent (at half the standard thrombolytic dosage) may be considered in selected patients (anterior MI, age <75 years, no risk factors for bleeding).97 However, other experts state that such combination therapy appears to provide little or no benefit.1016

ReoPro Dosage and Administration

General

  • Discontinue infusion in patients in whom PCI has failed.1

Adjunctive Antithrombotic Therapy: General Considerations

  • Used in conjunction with aspirin and heparin in clinical studies.1

  • Dosage of heparin required to maintain an appropriate activated clotting time (ACT) during concomitant therapy with abciximab may be lower than with heparin monotherapy.19 994 (See Specific Drugs under Interactions.)

Adjunctive Antithrombotic Therapy When Used to Prevent Acute Ischemic Complications of PCI

  • Aspirin: In clinical studies, patients received 325 mg 2 hours prior to PCI and daily thereafter.1 77 ACCF/AHA/SCAI recommends that aspirin 325 mg be given prior to PCI in patients not already receiving maintenance aspirin therapy.994 Patients already receiving maintenance aspirin therapy should receive a dose of 81–325 mg before the procedure.994

  • P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist: A loading dose of clopidogrel, prasugrel, or ticagrelor also is recommended prior to PCI in those undergoing stent placement.994

  • Heparin sodium: In clinical studies, patients received 70 units/kg if baseline ACT <150 seconds, 50 units/kg if baseline ACT was 150–199 seconds, or no heparin if baseline ACT ≥200 seconds; additional injections of 20 units/kg were given to maintain an ACT of ≥200 seconds during the procedure.1 Experts suggest use of lower dosages of concomitant IV heparin sodium (e.g., 50–70 units/kg) given 6 hours prior to PCI and targeted to an ACT of ≥200 seconds.10 12 16 19 45 46 77 994 (See Laboratory Monitoring under Cautions.) Postprocedural use of heparin generally not recommended.1 10 22 77

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV injection followed by IV infusion using a controlled-infusion device (e.g., pump).1

Do not shake vial.1

Filter injection upon dilution, prior to IV administration, or during IV infusion using a sterile, nonpyrogenic, low-protein-binding filter (0.2 or 5 mcm).1 7

For IV injection, withdraw appropriate dose into syringe and filter injection prior to administration.1

Discard unused portion.1

Do not admix or administer other drugs in the same IV line with abciximab injection or infusion.1

Dilution

For IV infusion, withdraw appropriate dose into syringe and inject into an appropriate container of 0.9% sodium chloride or 5% dextrose injection.1

Rate of Administration

For IV injection, administer over at least 1 minute.1 7

Dosage

Adults

Acute Ischemic Complications of PCI
IV

Patients undergoing PCI: 0.25 mg/kg by IV injection 10–60 minutes prior to PCI,1 7 followed by IV infusion of 0.125 mcg/kg per minute (maximum of 10 mcg/minute) for 12 hours.1

Patients scheduled to receive PCI within 24 hours: 0.25 mg/kg by IV injection, followed by IV infusion of 10 mcg/minute for 18–24 hours, concluding 1 hour after procedure.1 4

Prescribing Limits

Adults

Acute Ischemic Complications of PCI
IV

Patients undergoing PCI: Maximum 10 mcg/minute (as IV infusion) for 12 hours.1

Special Populations

No special population dosage recommendations at this time.1

Cautions for ReoPro

Contraindications

  • Bleeding diathesis, active internal bleeding, or recent (within 6 weeks) clinically important GI or genitourinary bleeding.1

  • Severe uncontrolled hypertension.1

  • Recent (within 6 weeks) major surgery or trauma.1

  • History of cerebrovascular accident (CVA) in preceding 2 years or CVA with serious substantial residual neurologic deficit.1

  • Recent (within previous 7 days) oral anticoagulant therapy unless prothrombin time (PT) is ≤1.2 times control value.1

  • Thrombocytopenia (platelet count <100,000/mm3).1

  • Intracranial neoplasm.1

  • Arteriovenous malformation or aneurysm.1

  • Use of IV dextran prior to or during PCI.1

  • Presumed or documented history of vasculitis.1

  • Known hypersensitivity to any ingredient in the formulation or to murine proteins.1 9

Warnings/Precautions

Warnings

Hematologic Effects

Risk of major bleeding (e.g., intracranial hemorrhage, genitourinary or GI bleeding, bleeding at arterial access site) and minor bleeding (e.g., spontaneous gross hematuria, spontaneous hematemesis); may require blood or platelet transfusions.1 2 4 5 (See Bleeding Precautions and see Laboratory Monitoring under Cautions.)

Pulmonary alveolar hemorrhage reported rarely.1

Increased risk of major bleeding observed in patients weighing ≤75 kg;1 4 5 during concomitant thrombolytic therapy;1 when PCI is performed within 12 hours of onset of symptoms of MI;1 following prolonged (>70 minutes) PCI;1 or following failed PCI.1 9

If bleeding cannot be controlled by pressure, discontinue abciximab and concomitant heparin immediately.1

Sensitivity Reactions

Hypersensitivity Reactions

Possible anaphylaxis.1 If anaphylaxis occurs, discontinue abciximab immediately and initiate appropriate treatment; drugs for treatment of hypersensitivity reactions (e.g., epinephrine, dopamine, theophylline, antihistamines, corticosteroids) should be immediately available.1

Formation of human antichimeric antibody (HACA) reported.1 3 8 16 22 23 54 63 65 Possible hypersensitivity reactions (including anaphylaxis), thrombocytopenia, or diminished antithrombotic effect if abciximab is readministered or if monoclonal antibodies are administered in patients with HACA titers.1

General Precautions

Bleeding Precautions

To reduce risk of bleeding, adhere to strict anticoagulation guidelines; use a short course of low-dose, weight-adjusted heparin; avoid vascular and other trauma; carefully manage vascular (e.g., femoral artery) access site; and monitor all potential bleeding sites during and following treatment.1 44 60

Use caution in the placement, maintenance, and removal of vascular access sheath; avoid femoral vein sheath placement.1 When inserting sheath, puncture only anterior wall of femoral artery; avoid Seldinger (through and through) technique.1 Observe appropriate precautions while sheath is in place (e.g., complete bed rest, elevation of head ≤30°, restrain limb in which sheath is inserted, frequent monitoring of vascular access site and distal pulse in the involved limb).1 Following PCI, discontinue heparin immediately; remove arterial sheath within 6 hours following PCI (at least 2 hours after discontinuation of heparin) if aPTT ≤50 seconds or ACT ≤175 seconds.1 Following sheath removal, apply pressure to femoral artery for at least 30 minutes to achieve hemostasis.1 Measure and monitor hematomas for enlargement.1

To avoid vascular and other trauma, minimize arterial or venous punctures, IM injections, cutdown sites, and use of nasotracheal intubation, nasogastric tubes, urinary catheters, and automatic BP cuffs; avoid establishment of IV access at noncompressible sites (e.g., subclavian or jugular veins); consider using an indwelling venipuncture device (e.g., heparin lock) for drawing blood; document and monitor vascular puncture sites; and remove dressings gently and carefully.1

If emergency surgery is needed, discontinue abciximab.1

Thrombocytopenia

Risk of thrombocytopenia.1 Severe thrombocytopenia (platelet count <20,000/mm3)19 46 66 reported more frequently than with tirofiban.1 32 54 67 68

Determine platelet count prior to treatment, at 2–4 hours following initial IV injection, and at 24 hours following initiation of therapy or prior to discharge, whichever occurs first.1 9 Consider possibility of pseudothrombocytopenia or heparin-induced thrombocytopenia (in patients receiving concomitant heparin therapy).1 14 47 54 59 70 Exclude pseudothrombocytopenia caused by an in vitro anticoagulant interaction by sampling blood in tubes containing edetate disodium (EDTA), citrate, or heparin.1 A low platelet count in the presence of EDTA but not in the presence of heparin and/or citrate supports of a diagnosis of pseudothrombocytopenia.1

If true thrombocytopenia is verified, discontinue abciximab and initiate appropriate treatment and monitoring.1 Platelet transfusions may partially restore platelet function.1

Possible increased incidence and severity of thrombocytopenia following readministration.1

Contraindicated in patients with platelet counts <100,000/mm3.1

Laboratory Monitoring

Prior to administration, obtain platelet count, PT, ACT, and aPTT.1

Monitor platelet count during and after treatment.1 (See Thrombocytopenia under Cautions.)

When abciximab is initiated 18–24 hours prior to PCI, maintain aPTT between 60–85 seconds.1 During PCI, maintain ACT ≥200 seconds.1 10 12 16 19 45 46 77 If anticoagulation is continued following PCI, maintain aPTT between 55–75 seconds.1

Monitor aPTT or ACT prior to arterial sheath removal; do not remove sheath unless aPTT ≤50 seconds or ACT is 150–180 seconds (approximately 6 hours after PCI).1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether abciximab is distributed into milk.1 Use with caution.1 9

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 9

Geriatric Use

No substantial differences in safety and efficacy in patients 65–74 years of age relative to younger adults.1 Insufficient experience in patients ≥75 years of age to determine whether these patients respond differently than younger adults.1

Common Adverse Effects

Bleeding, back pain, hypotension, nausea, chest pain, vomiting, headache, bradycardia, puncture site pain, abdominal pain, peripheral edema.1

Interactions for ReoPro

No formal drug interaction studies to date.1

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral

Potential increased risk of bleeding1

Use with caution1

Dextran

Increased risk of bleeding1

Concomitant use contraindicated1

Dipyridamole

Potential increased risk of bleeding1

Use with caution1

Heparin

Increased risk of bleeding1

Monitor aPTT or ACT during therapy1

NSAIAs

Potential increased risk of bleeding1

Use with caution1

Thrombolytics (e.g., reteplase)

Increased risk of major bleeding1

Weigh risk against anticipated benefit of concomitant therapy1

Ticlopidine

Potential increased risk of bleeding1

Use with caution1

ReoPro Pharmacokinetics

Absorption

Onset

Maximal inhibition of platelet aggregation occurs within 10 minutes following IV administration.1

Duration

Bleeding time returns to ≤12 minutes within 12–24 hours following discontinuance of infusion.1 Platelet function generally recovers within 48 hours.1

Distribution

Extent

Not known whether abciximab is distributed into breast milk or is absorbed systemically after ingestion.1

Elimination

Half-life

Initial half-life is <10 minutes; second phase half-life is about 30 minutes.1 Abciximab remains in circulation for ≥15 days in a platelet-bound state.1

Stability

Storage

Parenteral

Injection

2–8°C.1 Do not freeze.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

No incompatibilities observed with glass bottles, PVC bags, or IV administration sets.1

Solution Compatibility1

No incompatibilities observed with IV fluids.1

Compatible

Dextrose 5%

Sodium chloride 0.9%

Drug Compatibility

No incompatibilities observed with commonly used cardiovascular drugs.1 Nevertheless, administer abciximab in separate IV line whenever possible; do not mix with other drugs.1

Y-Site CompatibilityHID

Compatible

Adenosine111

Atropine sulfate111

Bivalirudin

Diphenhydramine HCl111

Fentanyl citrate111

Metoprolol tartrate111

Midazolam HCl111

Actions

  • Fab fragment of chimeric human-murine monoclonal immunoglobulin antibody 7E3.1 2 3 4 5 6

  • Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa receptors).1 2 4 5

Advice to Patients

  • Risk of serious bleeding or hemorrhage.1 4 5 9

  • Importance of close laboratory monitoring.1

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of advising patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Abciximab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

2 mg/mL (10 mg)

ReoPro

Lilly

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 15, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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5. Anon. Centocor will begin shipping Reopro to Lilly in early January: Reopro is the first GpIIbIIIa antagonist for PTCA patients at high risk for ischemic complications. F-D-C Rep. 1995 Jan:16-7.

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9. Eli Lilly and Company, Indianapolis, IN: Personal communication.

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72. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med. 1995; 332:1553-9. [IDIS 348226] [PubMed 7739710]

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74. Lincoff AM, Tcheng JE, Califf RM et al. Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one year outcome in the EPILOG trial. Circ. 1999; 99:1951-8.

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