Abciximab


Article Author:
Kevin Stoffer


Article Editor:
Saumya Shah


Editors In Chief:
Russell McAllister
Jason Widrich
Daniel Sizemore


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
7/17/2019 1:42:13 PM

Indications

Abciximab has been studied in three phase 3 clinical trials: EPIC, EPILOG, and CAPTURE. 

Here is how abciximab is currently being used. It is a prescription-only medication and is only indicated for intravenous (IV) use. Further studies and randomized controlled trials (RCTs) need to be conducted to provide more interventions for this drug. Studies have shown abciximab to be effective in the prevention of ischemic cardiac complications in patients undergoing percutaneous coronary intervention and prevention of ischemic cardiac complications in patients with unstable angina (UA)/non-ST-elevation myocardial infarction (NSTMI) unresponsive to conventional therapy when PCI is scheduled within 24 hours.  Abciximab has only been studied in use with aspirin and heparin.[1][2][3]

FDA-labeled indications

  • Myocardial ischemia: Prophylaxis and adjunct therapy to PCI
  • PCI: Adjunct, refractory unstable angina

Non-FDA-labeled indications

  • Acute myocardial infarction: cardiogenic shock
  • Aneurysm of coronary vessels: such as with Kawasaki disease
  • Acute arterial thrombosis
  • Myocardial infarction

Mechanism of Action

Abciximab is the Fab antibody fragment of chimeric human-murine monoclonal antibody 7E3. Inhibits platelet aggregation by reversibly binding to platelet IIb/IIIa receptors, which in turn results in steric hindrance. It prevents the binding of fibrinogen, von Willebrand factor, and other adhesive molecules during clot formation. A second action which has not been studied is the impact of Abciximab binding onto the Mac-1 integrin receptor on activated monocytes. Inhibition is produced in a dose-dependent fashion. This produces an environment similar to the autosomal recessive disease Glanzmann thrombasthenia, which is marked by an inherent decrease in GPIIB-IIa receptors on the surface of the platelet. Laboratory findings in this condition include an increased bleeding time with no change in platelet count, PT or PTT.  Do not confuse this with the pathogenesis of Von Willebrand disease or Bernard-Soulier syndrome. These are diseases of platelet adhesion, in contrast to Glanzmann thrombasthenia, which is a disorder of platelet aggregation. Clopidogrel and ticagrelor are drugs that decrease platelet adhesion and are useful in preventing ischemic stroke. Platelet adhesion is a commonly mistaken mechanism for abciximab. Abciximab produces its effect over a short half-life of approximately 30 minutes, allowing it to be used as a short-term platelet aggregation inhibitor on the way to the cath lab for PCI. The free plasma concentrations of abciximab decrease rapidly. There is an initial half-life of less than 10 minutes. The second phase half-life is about 30 minutes.Its effects on platelets last for 48 hours after administration and can still be seen in low potency up to 15 days after administration.[4][5]

Administration

Typically supplied as Reopro IV solution of 2 mg/1 ml.

Percutaneous coronary intervention (PCI): 0.25 mg/kg IV bolus administered 10 to 60 minutes before the start of PCI followed by infusion of 0.125 mcg/kg/min for 12 hours, not to exceed 10 mcg per minute. 

Unstable angina/non-ST-elevation MI (UA/NSTEMI) unresponsive to conventional medical therapy with planned PCI within 24 hours: 0.25 mg/kg IV bolus followed by an 18 t 24-hour infusion of 10 mcg/min, concluding one hour after PCI.  An ACT of 300 seconds and an aPTT of 70 seconds should be aimed for while completing PCI. Dosage does not need to be changed for patients with renal failure.

Infuse at a maximum rate of 10 mcg per minute and do not mix with other drugs.

Aneurysm of coronary vessels: Kawasaki disease (off-label use, 2 months to 7 years) 0.25 mg/kg IV loading dose by bolus, followed by an infusion of 0.125 mcg/kg/minute for 12 hours. Standard therapy includes IV gamma globulin 2 gm/kg, give 24 to 48 hours before abciximab, and aspirin 80 to 100 mg/kg per day. All subjects were heparinized and also stabilized on warfarin before hospital discharge (study dosage).

Adverse Effects

The most common adverse effects are chest pain, hypotension, injection site pain, abdominal pain, nausea, vomiting, minor hemorrhage, gross hematuria, and backache.[6][7]

Rare but severe side effects include thrombocytopenia, anaphylaxis, major hemorrhage (cerebrovascular, pulmonary), and non-hemorrhagic cerebrovascular accident.

Abciximab administration is not associated with a higher risk of bleeding in those undergoing CABG treatment.

Pregnancy category C risk has not been ruled out. Infant risk while breastfeeding has not been studied.

Contraindications

All of the followings are contraindications for the use of abciximab:

  • Hypersensitivity to abciximab or component of formulation
  • Recent (within 6 weeks) clinically significant gastrointestinal (GI) or genitourinary (GU) bleeding or active internal hemorrhage
  • Within 2 years of cerebrovascular accident or with significant neurological deficit
  • Clotting abnormalities or within 7 days of administration of oral anticoagulants unless prothrombin time (PT) is 1.2 times control PT value or lower
  • Thrombocytopenia (less than 100,000 cells/uL)
  • Within 6 weeks of major surgery or trauma
  • Intracranial tumor
  • Arteriovenous malformation or an 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
  • Oral anticoagulant use within the last seven days unless a PT time of 1.2 times the control or less
  • Vasculitis: clinical or documented diagnosis
  • Hypertension, severely uncontrolled
  • Theoretical contraindications exist for coadministration with defibrotide and eptifibatide. Interactions may increase the risk of hemorrhage.

Monitoring

Monitor complete blood counts (CBCs), prothrombin time (PT), activated clotting time, and signs and symptoms of bleeding.

  • CBC: look for thrombocytopenia and anemia due to occult hemorrhage
  • PT/aPTT: monitor the risk of bleeding
  • Chest x-ray if signs of hemoptysis

Toxicity

There is not a minimum toxic dose listed. It is advised to begin with the therapeutic dose and to monitor patient response carefully. There is not enough research to verify the efficacy or safety of abciximab use in pediatric patients.[8][9][10]

Approximately 5% of those treated with abciximab will develop bleeding, but due to inpatient administration, overdose is highly unlikely. In several case reports, gastrointestinal bleeding and thrombocytopenia have been described as adverse effects.  Bleeding at infusion sites is the most common adverse effect and would likely worsen at toxic levels. Infusion with COX inhibitors or other anti-platelet drugs increases the risk for toxicity and adverse effects.

In the event of toxicity or adverse effects, transfuse the patient with platelets with severe thrombocytopenia. If the patient becomes hypotensive, deliver a fluid bolus.

No antidote exists for reversing abciximab.

Hemodialysis may be used to remove toxic levels of the drug successfully.

Toxic/adverse effects of abciximab are quality for admission criteria due to the need for continuous monitoring of hematologic stability.

Important questions and considerations to ask about or explain to the patient before use include:

  • Have you used any anticoagulants in the last 7 days
  • Information about treatments if bleeding occurs
  • Information about monitoring for lab abnormalities
  • Importance of rest after the infusion
  • Instruction to avoid bruises and lacerations after the infusion
  • Instruction to return to hospital with any new signs of bleeding or syncope

Enhancing Healthcare Team Outcomes

Abciximab is widely used in interventional cardiology for the treatment of unstable angina and as an adjunct therapy following percutaneous coronary intervention. The drug is only used intravenously. Healthcare workers including nurses, pharmacists, and clinicians should be aware that one of the most common complications of abciximab is bleeding and work together as a team to identify this complication early. Patients who receive this agent must be monitored for bleeding at the IV access site and the groin. Because there is no specific antidote to reverse bleeding, it is vital to avoid other anticoagulants at the same time. In addition, the platelet count must be followed since abciximab can cause thrombocytopenia. If bleeding occurs, a consult with the hematologist is highly recommended.


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Abciximab - Questions

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Which monoclonal antibody is directed against the glycoprotein platelet receptor?



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Which monoclonal antibody with activity against the platelet GP2b/3a receptor is used in angioplasty?



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Which antiplatelet drug is an antibody to the platelet receptor?



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A 62-year-old is admitted with chest pain. ECG reveals that he is having an acute myocardial infarction. There is no cardiac catheterization facility nearby, and he is started on a drug that is an antibody to the platelet receptor. Which of the following is the drug?



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Which of the following does not occur when combining stenting with abciximab?



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A patient has unstable angina of 48 hours duration. An angiography shows near occlusion of the proximal left anterior descending coronary artery. Which treatment modality will reduce cardiac enzyme leak during revascularization?



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What is the correct dose of abciximab after percutaneous transluminal coronary angioplasty?



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What is the target activated clotting time for patients receiving abciximab?



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What is the half-life of abciximab?



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How long should an emergent coronary artery bypass grafting (CABG) be delayed after a dose of abciximab?



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Which of the following statements is TRUE regarding acute severe thrombocytopenia due to abciximab?



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Which of the following is true regarding thrombocytopenia after coronary artery intervention?



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Which drug can block Glycoprotein IIb/IIIa (GPIIb-IIIB) receptors on the platelets?



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Which is true about abciximab?



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What is the dose for abciximab after percutaneous intervention?



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A 65-year old undergoes an angioplasty for acute coronary syndrome. The cardiologist recommends using the anti-platelet drug that is an antibody to the platelet receptor. What will you order for the patient?



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A 67-year-old male presents to the emergency department 2 hours after the onset of chest pain. He reports that his pain is dull in quality and crushing in nature. His pain radiates to his right shoulder, and he is experiencing nausea. He has taken two 81mg aspirin and a sublingual nitroglycerin prescribed by his primary care physician for stable angina. His EKG on admission shows ST elevations in three contiguous leads. On the way to the cath lab, he receives a medication known to prevent complications in those undergoing percutaneous coronary intervention, what step of platelet function is inhibited by this medication?



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A new drug is being considered to alter platelet aggregation. Which of the following molecular targets could be considered in the pharmacologist's research?



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Which of the following drugs inhibit platelet aggregation only?



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Abciximab - References

References

Bedjaoui A,Allal K,Lounes MS,Belhadi CE,Mekarnia A,Sediki S,Kara M,Azaza A,Monsuez JJ,Benkhedda S, Intracoronary or intravenous abciximab after aspiration thrombectomy in patients with STEMI undergoing primary percutaneous coronary intervention. Cardiovascular journal of Africa. 2018 Nov 20     [PubMed]
Morales-Ponce FJ,Lozano-Cid FJ,Martinez-Romero P,Gonzalez-Perez P,Sanchez-Brotons JA,Diaz-Torres I,Rodriguez-Yanez JC,Caro-Mateo P,Serrador-Frutos AM, Intracoronary Tenecteplase versus Abciximab as Adjunctive Treatment during Primary Percutaneous Coronary Intervention in Patients with Anterior Myocardial Infarction. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. 2018 Nov 13     [PubMed]
Ortiz-Otero N,Mohamed Z,King MR, Platelet-Based Drug Delivery for Cancer Applications. Advances in experimental medicine and biology. 2018     [PubMed]
Delgado F,Oteros R,Jimenez-Gomez E,Bravo Rey I,Bautista MD,Valverde Moyano R, Half bolus dose of intravenous abciximab is safe and effective in the setting of acute stroke endovascular treatment. Journal of neurointerventional surgery. 2018 Aug 28     [PubMed]
Abciximab null. 2006     [PubMed]
Golden T,Ghazala S,Wadeea R,Junna S, Abciximab-induced acute profound thrombocytopenia postpercutaneous coronary intervention. BMJ case reports. 2017 Jul 14     [PubMed]
Rubboli A,Patti G, What is the Role for Glycoprotein IIb/IIIa Inhibitor Use in the Catheterization Laboratory in the Current Era? Current vascular pharmacology. 2018     [PubMed]
Piątek Ł,Janion-Sadowska A,Kurzawski J,Grabowska U,Janion M, Delayed severe abciximab-induced thrombocytopenia: A case report. Heart     [PubMed]
De Rosa S,Caiazzo G,Torella D,Indolfi C, Intracoronary versus intravenous abciximab bolus administration. Journal of the American College of Cardiology. 2014 Apr 8     [PubMed]
Sami S,Willerson JT, Contemporary treatment of unstable angina and non-ST-segment-elevation myocardial infarction (part 2). Texas Heart Institute journal. 2010     [PubMed]

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