Eptifibatide (Integrilin) is a cyclic heptapeptide that is derived from a disintegrin protein found in rattlesnake venom. It acts as an antiplatelet drug that selectively and reversibly inhibits Glycoprotein IIb/IIIa receptor.

Eptifibatide (Integrilin) Uses:

• Non-ST elevation acute coronary syndromes:

  • Used in the treatment of patients with unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI), including patients who are to be managed medically and those undergoing percutaneous coronary intervention (PCI).

• Percutaneous coronary intervention with or without coronary stenting:

  • Treatment of patients undergoing PCI, including those undergoing coronary stenting.

• Off Label Use of Eptifibatide in Adults:

  • ST-elevation myocardial infarction

Eptifibatide (Integrilin) Dose in Adults

Eptifibatide (Integrilin) Dose in the treatment of Ischemic heart disease:

• Acute coronary syndrome:

  • Note:
    • Initial therapy for acute coronary syndrome (ACS) typically includes oral antiplatelet therapy (eg, aspirin plus a P2Y12 inhibitor) and an IV anticoagulant (eg, bivalirudin or heparin).
    • A glycoprotein (GP) IIb/IIIa inhibitor is not routinely used due to limited benefit on ischemic outcomes and more bleeding complications.
    • However, use may be considered in high-risk patients when a percutaneous coronary intervention (PCI) is planned.
    • Some experts consider a GP IIb/IIIa inhibitor if ticagrelor or prasugrel was not the P2Y12 inhibitor of choice when the duration between P2Y12 inhibitor administration and PCI is short (eg,  less than 30 to 45 minutes), or for significant thrombus burden.

• Non-ST elevation acute coronary syndromes:

• Note: Begin after diagnostic coronary angiography, just before PCI.
  • IV: Bolus of 180 mcg per kg (maximum: 22.6 mg), followed by a continuous infusion of 2 mcg per kg per minute (maximum: 15 mg per hour);
  • a second bolus of 180 mcg per kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus; may continue infusion for up to 18 to 24 hours after PCI.

• ST-elevation myocardial infarction (off-label use):

Note: Begin after diagnostic coronary angiography, just before PCI.

• IV: Bolus of 180 mcg per kg (maximum: 22.6 mg), followed by a continuous infusion of 2 mcg per kg per minute (maximum: 15 mg/hour);
• A second bolus of 180 mcg per kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus;
• may continue infusion for up to 18 to 24 hours after PCI.

• Percutaneous coronary intervention with or without coronary stenting:

Note:

• Aspirin, a P2Y12 inhibitor (eg, prasugrel, clopidogrel,  or ticagrelor) and an IV anticoagulant (eg, bivalirudin or heparin) are recommended prior to PCI.
• A GP IIb/IIIa inhibitor is typically not recommended for elective PCI unless a patient is at high risk for acute stent thrombosis or was not adequately pretreated with a P2Y12 inhibitor.
  • IV: Bolus of 180 mcg per kg (maximum: 22.6 mg) administered immediately before PCI, followed by a continuous infusion of 2 mcg per kg per minute (maximum: 15 mg per hour);
  • A second bolus of 180 mcg per kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus; may continue infusion for 2 to 24 hours after PCI.

Note:

• If CABG is performed, some experts recommend discontinuing eptifibatide ≥2 to 4 hours before surgery.
• The pharmacokinetic studies indicate that platelet function is restored ~4 to 8 hours after discontinuation.

Use in Children:

Not indicated.

Eptifibatide (Integrilin) Pregnancy Risk Factor B

• Animal reproduction studies have not shown any adverse events.

Eptifibatide use during breastfeeding:

• Manufacturer recommends caution when giving eptifibatide as a nursing drug to women.
• It is unknown if eptifibatide can be found in breast milk.

Eptifibatide (Integrilin) Dose in Kidney Disease:

Note: The Cockcroft-Gault equation using actual body weight should be used to estimate renal function.

• Acute coronary syndrome (non-ST elevation acute coronary syndromes or ST-elevation myocardial infarction [off-label use]):

  • CrCl ≥50 mL/minute:
    • No dosage adjustment required.
  • CrCl <50 mL/minute:
    • IV: Bolus 180 mcg/kg (maximum: 22.6 mg), followed by a continuous infusion of 1 mcg per kg per minute (maximum: 7.5 mg/hour).
  • End-stage renal disease (ie, dialysis-dependent):
    • Use is contraindicated.

• Percutaneous coronary intervention with or without coronary stenting:

  • CrCl ≥50 mL/minute:
    • No dosage adjustment required.
  • CrCl <50 mL/minute:
    • IV: Bolus of 180 mcg per kg (maximum: 22.6 mg) administered immediately before PCI and followed by a continuous infusion of 1 mcg per kg per minute (maximum: 7.5 mg per hour).
    • Administer a second bolus of 180 mcg per kg (maximum: 22.6 mg) 10 minutes after the first bolus.
  • End-stage renal disease (ie, dialysis-dependent):
    • Use is contraindicated.
  • Hemodialysis:
    • It is dialyzable: ~73 to 83 percent removed after 1 hour.

Eptifibatide (Integrilin) Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling doesn't provide any dosage adjustments (has not been studied).

Bleeding is a major drug-related adverse effect. The access site is often the primary source of bleeding complications. The incidence of bleeding is also related to heparin intensity. Patients weighing less than 70 kg may have an increased risk of major bleeding.

Common Side Effects of Eptifibatide (Integrilin):

• Hematologic: & oncologic:

  • Hemorrhage

Less Common Side Effects of Eptifibatide (Integrilin):

• Cardiovascular:

  • Hypotension

• Hematologic & oncologic:

  • Thrombocytopenia includes
    • Acute profound thrombocytopenia
    • Immune-mediated thrombocytopenia

• Local:

  • Injection site reaction

Contraindications to Eptifibatide (Integrilin):

• Hypersensitivity to eptifibatide and any component of the formulation
• Active abnormal bleeding in the last 30 days, or a history bleeding diathesis
• History of stroke in the last 30 days, or hemorhagic stroke.
• Antihypertensive therapy is not effective in treating severe hypertension (systolic or diastolic bloodpressures greater than 200 mmHg).
• Major surgery in the past 6 weeks
• Current or planned administration of another parenteral GP IIb/IIIa inhibitor
• Dependence on hemodialysis

Canadian labeling: Additional contraindications not in U.S. Labeling

• PT >1.2x control or INR >=2.0
• The history of intracranial diseases (eg, neoplasms, arteriovenous malformations, aneurysm) is known
• Grave renal impairment (CrCl 30mL/minute);
• thrombocytopenia (<100,000 cells/mm3);
• Clinically significant liver disease

Warnings and precautions

• Bleeding

  • Bleeding is the most common complication, including retroperitoneal and pulmonary bleeding and spontaneous GI or GU bleeding.
  • Watch out for bleeding, particularly at the site of cardiac catheterization.
  • Patients with a body weight less than 70 kg could be at higher risk of major and minor bleeding.
  • An older age and a history of bleeding disorders are risk factors for bleeding.
  • Reduce invasive procedures such as arterial and venous punctures and IM injections.

• Hypersensitivity

  • Hypersensitivity reactions, such as anaphylaxis or urticaria, have been reported.

• Thrombocytopenia:

  • An acute, severe form of thrombocytopenia (immune-mediated or nonimmune mediated), has been reported and can occur as soon as 24 hours after initiation.
  • After discontinuation, platelet counts should quickly recover (within 1-5 business days).
  • Patients with platelet counts below 100,000/mm should be used with caution (as indicated in the Canadian labeling).
  • Published are specific management guidelines for GP IIb/IIIa induced thrombocytopenia.
  • If the platelet count drops to 100,000./mm3 during therapy discontinue eptifibatide or heparin concurrently.

• Renal impairment

  • Patients with renal dysfunction (estimated CRCl less than 50mL per hour, using the Cockcroft-Gault formula) should be cautious. Dosage adjustment may be necessary.
  • Patients who are dependent on hemodialysis should not use it.

Eptifibatide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Coagulation parameters, signs/symptoms of excessive bleeding.
• Laboratory tests at baseline and monitoring during therapy:
  • hematocrit and hemoglobin,
  • serum creatinine,
  • PT/aPTT (maintain aPTT between 50-70 seconds unless PCI is to be performed), and ACT with PCI (maintain ACT between 200-300 seconds during PCI).
  • Platelet count recommended at 2-4 hours after initiation, and at 24 hours or prior to discharge, whichever is first.
• Assess the sheath insertion site and distal pulses of the 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 bed rest 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, and examine urine, stool, and emesis for the presence of occult or frank blood; gentle care should be provided when removing dressings.

How to administer Eptifibatide (Integrilin)?

IV:

• Bolus dose should be withdrawn from the 10 mL vial into a syringe and administered by IV push.
• Begin continuous infusion (using an IV infusion pump) immediately following bolus administration, administered undiluted directly from the 100 mL vial.
• The 100 mL vial should be spiked with a vented infusion set.

Mechanism of action of Eptifibatide (Integrilin):

• Eptifibatide, a cyclic pentapeptide, blocks the platelet glycoprotein IIb/IIIa, which is the binding site of fibrinogen, von Willebrand factors, and other ligands.
• This final common receptor can be inhibited to block platelet aggregation and prevent thrombosis.

The onset of action:

• Immediate after initial bolus ( more than 80 percent  inhibition of ADP-induced aggregation achieved 5 minutes after bolus dose);
• The maximal effect achieved within 1 hour.

Duration:

• Platelet function restored ~4 to 8 hours following discontinuation.

Protein binding:

• ~25 percent

Half-life elimination:

• ~2.5 hours

Excretion:

• Primarily urine (as eptifibatide and metabolites)

Clearance:

• Total body: ~55 mL/kg/hour;
• Renal: ~50% of total body clearance in healthy subjects

International Brands of Eptifibatide:

• Integrilin
• Integrillin
• Antigrilin
• Integril

Eptifibatide Brand Names in Pakistan: