Usage
Eptifibatide is prescribed for the reduction of death and/or myocardial infarction in patients with unstable angina (UA) or non-Q-wave myocardial infarction (NQMI), including those who are to be managed medically and those who will undergo percutaneous coronary intervention (PCI). It is also indicated for patients undergoing PCI, including those who will receive intracoronary stents.
It is classified as a platelet aggregation inhibitor, specifically a glycoprotein IIb/IIIa inhibitor.
Eptifibatide’s mechanism of action involves the prevention of platelet aggregation by reversibly blocking the platelet glycoprotein (GP) IIb/IIIa receptor. This receptor is the major receptor involved in platelet cross-linking.
Alternate Names
Integrilin is the brand name for eptifibatide.
How It Works
Pharmacodynamics: Eptifibatide inhibits platelet aggregation by reversibly binding to the platelet GP IIb/IIIa receptor. This prevents fibrinogen, von Willebrand factor, and other adhesive ligands from binding to the receptor and causing platelet aggregation. It does not significantly affect other platelet functions such as shape change or serotonin release.
Pharmacokinetics:
- Absorption: Administered intravenously, therefore bioavailability is 100%. Peak plasma concentrations are reached immediately after bolus administration.
- Distribution: Distributes rapidly in the vascular compartment. Approximately 25% of eptifibatide is bound to plasma proteins.
- Metabolism: No major metabolites of eptifibatide have been detected in human plasma.
- Elimination: Primarily eliminated by the kidneys. Clearance is reduced by about 50% in patients with moderate to severe renal impairment.
Mode of Action: Eptifibatide competitively and reversibly binds to the GP IIb/IIIa receptor on the platelet surface, specifically targeting the arginine-glycine-aspartic acid (RGD) sequence recognition site. This blockage prevents the binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa, ultimately preventing platelet aggregation and thrombus formation.
Receptor Binding: Binds to the GP IIb/IIIa receptor.
Elimination Pathways: Primarily renal excretion with minimal hepatic metabolism.
Dosage
Standard Dosage
Adults:
- UA/NQMI: 180 mcg/kg IV bolus as soon as possible after diagnosis, followed by a continuous infusion of 2 mcg/kg/min for up to 72 hours, until coronary artery bypass graft (CABG) surgery or hospital discharge. If PCI is performed, continue infusion for 20-24 hours post-PCI, up to a maximum of 96 hours total.
- PCI: 180 mcg/kg IV bolus immediately before the procedure, followed by a second 180 mcg/kg bolus 10 minutes later. Simultaneously with the first bolus, initiate a continuous infusion of 2 mcg/kg/min until hospital discharge or for up to 18-24 hours post-PCI (minimum 12 hours).
Children: Not recommended for use in children under 18 years of age due to insufficient safety and efficacy data.
Special Cases:
- Elderly Patients: Increased risk of bleeding. Close monitoring and dosage adjustments based on renal function are necessary.
- Patients with Renal Impairment:
- Creatinine Clearance (CrCl) 30-50 mL/min: 1 mcg/kg/min continuous infusion. Bolus dose remains the same.
- CrCl < 30 mL/min: Contraindicated.
- Patients with Hepatic Dysfunction: Use with caution. No specific dosage adjustment guidelines are available, but close monitoring is recommended.
- Patients with Comorbid Conditions: Close monitoring, particularly for patients with conditions that increase bleeding risk.
Clinical Use Cases
Eptifibatide’s clinical use is focused on acute coronary syndromes and PCI. Therefore, dosage recommendations align with the standard dosage guidelines mentioned above. Its use in settings like intubation, surgical procedures unrelated to PCI, mechanical ventilation, and the ICU would be determined by specific patient needs and in conjunction with standard acute coronary syndrome treatment.
Dosage Adjustments
Dose adjustments are primarily based on renal function, as described above. Other patient-specific factors such as age, weight, and concomitant medications should also be considered.
Side Effects
Common Side Effects
Bleeding (e.g., at the site of catheter insertion, gastrointestinal, genitourinary), thrombocytopenia, hypotension.
Rare but Serious Side Effects
Severe or life-threatening bleeding (e.g., intracranial hemorrhage, retroperitoneal bleeding), profound thrombocytopenia, allergic reactions (e.g., anaphylaxis).
Long-Term Effects
Long-term effects are unlikely due to the short-term use of eptifibatide.
Adverse Drug Reactions (ADR)
Severe bleeding and anaphylaxis require immediate medical attention. Profound thrombocytopenia necessitates close monitoring and potential discontinuation of therapy.
Contraindications
Active bleeding, history of stroke within 30 days, any history of hemorrhagic stroke, intracranial disease (neoplasm, arteriovenous malformation, aneurysm), major surgery or severe trauma within the past 6 weeks, bleeding diathesis, thrombocytopenia (<100,000 cells/mm³), severe hypertension, severe renal impairment (CrCl < 30 mL/min), clinically significant hepatic impairment, hypersensitivity to eptifibatide, concomitant or planned administration of another parenteral GP IIb/IIIa inhibitor.
Drug Interactions
Other antiplatelet agents (e.g., aspirin, clopidogrel, ticlopidine), anticoagulants (e.g., heparin, warfarin), thrombolytics, NSAIDs, dipyridamole. Coadministration of these medications can increase the risk of bleeding.
Pregnancy and Breastfeeding
Pregnancy Safety Category: B. While animal studies have not shown fetal harm, there are no adequate and well-controlled studies in pregnant women. Eptifibatide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breastfeeding: It is unknown if eptifibatide is excreted in human milk. Due to the potential for adverse reactions in the nursing infant, it is recommended to interrupt breastfeeding during treatment.
Drug Profile Summary
- Mechanism of Action: Reversibly inhibits platelet aggregation by blocking the GP IIb/IIIa receptor.
- Side Effects: Bleeding, thrombocytopenia, hypotension.
- Contraindications: Active bleeding, recent stroke, intracranial disease, severe renal impairment, severe hypertension.
- Drug Interactions: Other antiplatelet agents, anticoagulants, thrombolytics, NSAIDs.
- Pregnancy & Breastfeeding: Category B; not known if excreted in breast milk – interrupt breastfeeding.
- Dosage: Adults: UA/NQMI and PCI: 180 mcg/kg IV bolus followed by infusion (see dosage section for details).
- Monitoring Parameters: Platelet count, hemoglobin, hematocrit, serum creatinine, PT/INR, aPTT, ACT (during PCI).
Popular Combinations
Eptifibatide is commonly used in combination with aspirin and heparin, especially in the setting of PCI. This combination provides synergistic antithrombotic effects.
Precautions
Closely monitor for bleeding, especially in elderly patients, those with renal impairment, and those receiving concomitant medications that increase bleeding risk. Monitor platelet counts, hemoglobin, hematocrit, and coagulation parameters.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Eptifibatide?
A: The dosage depends on the indication (UA/NQMI or PCI) and renal function. Please refer to the detailed dosage section above.
Q2: What is the mechanism of action of Eptifibatide?
A: Eptifibatide inhibits platelet aggregation by reversibly blocking the platelet GP IIb/IIIa receptor.
Q3: What are the most common side effects of Eptifibatide?
A: Bleeding, thrombocytopenia, and hypotension.
Q4: What are the contraindications for using Eptifibatide?
A: Active bleeding, recent stroke, intracranial disease, severe renal impairment, severe hypertension, and hypersensitivity are some of the contraindications.
Q5: How is Eptifibatide administered?
A: Eptifibatide is administered intravenously via bolus injection followed by continuous infusion.
Q6: Can Eptifibatide be used in patients with renal impairment?
A: Dosage adjustments are needed for patients with moderate renal impairment. It is contraindicated in patients with severe renal impairment (CrCl < 30 mL/min).
Q7: What are the key monitoring parameters for patients receiving Eptifibatide?
A: Platelet count, hemoglobin, hematocrit, serum creatinine, PT/INR, aPTT, and ACT (during PCI).
Q8: Can Eptifibatide be used during pregnancy?
A: Eptifibatide is a Pregnancy Category B drug. It should only be used if the potential benefit justifies the potential risk to the fetus.
Q9: Is Eptifibatide compatible with all intravenous solutions?
A: Eptifibatide is incompatible with furosemide. It should not be mixed with other medications unless compatibility has been established.
Q10: What should be done if a patient experiences severe bleeding while receiving Eptifibatide?
A: Eptifibatide and any concomitant heparin should be discontinued immediately. Apply pressure to the bleeding site and provide supportive care as needed.
