Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Integrilin: 75 mg/100 mL (100 mL); 20 mg/10 mL (10 mL); 200 mg/100 mL (100 mL)
Generic: 75 mg/100 mL (100 mL); 20 mg/10 mL (10 mL)
Solution, Intravenous [preservative free]:
Generic: 75 mg/100 mL (100 mL); 20 mg/10 mL (10 mL); 200 mg/100 mL (100 mL)
Pharmacology
Mechanism of Action
Eptifibatide is a cyclic heptapeptide which blocks the platelet glycoprotein IIb/IIIa receptor, the binding site for fibrinogen, von Willebrand factor, and other ligands. Inhibition of binding at this final common receptor reversibly blocks platelet aggregation and prevents thrombosis.
Pharmacokinetics/Pharmacodynamics
Excretion
Primarily urine (as eptifibatide and metabolites)
Clearance: Total body: ~55 mL/kg/hour; Renal: ~50% of total body clearance in healthy subjects
Onset of Action
Immediate after initial bolus (>80% inhibition of ADP-induced aggregation achieved 5 minutes after bolus dose); maximal effect achieved within 1 hour (Gilchrist, 2001; Tardiff, 2001)
Duration of Action
Platelet function restored ~4 to 8 hours following discontinuation (Tardiff, 2001)
Half-Life Elimination
~2.5 hours
Protein Binding
~25%
Use in Specific Populations
Special Populations: Renal Function Impairment
Clearance reduced approximately 50% and steady-state plasma levels are approximately doubled in patients with moderate to severe renal function impairment (CrCl less than 50 mL/minute).
Special Populations: Elderly
Higher plasma levels and lower total body clearance.
Use: Labeled Indications
Non-ST elevation acute coronary syndromes: 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.
Use: Off Label
ST-elevation myocardial infarctionbyes
Data from an international, multicenter, randomized, prospective, open parallel group comparison of eptifibatide versus abciximab (in combination with other antiplatelet and anticoagulant therapy) supports the use of eptifibatide in this setting Zeymer 2010. In a large registry conducted in Sweden, results suggested that eptifibatide is noninferior to abciximab in patients with STEMI undergoing PCI with respect to death or MI during 1 year and also supports the use of eptifibatide in this setting Åkerblom 2010.
Based on the 2013 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for the management of ST-elevation myocardial infarction, eptifibatide may be used to support percutaneous coronary intervention (PCI) during STEMI when administered at the time of PCI.
Contraindications
Hypersensitivity to eptifibatide or any component of the formulation; active abnormal bleeding within the previous 30 days or a history of bleeding diathesis; history of stroke within 30 days or a history of hemorrhagic stroke; severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately controlled on antihypertensive therapy; major surgery within the preceding 6 weeks; current or planned administration of another parenteral GP IIb/IIIa inhibitor; dependency on hemodialysis
Canadian labeling: Additional contraindications (not in U.S. labeling): PT >1.2 times control or INR ≥2.0; known history of intracranial disease (eg, neoplasm, arteriovenous malformation, aneurysm); severe renal impairment (CrCl <30 mL/minute); thrombocytopenia (<100,000 cells/mm3); clinically significant liver disease
Dosage and Administration
Dosing: Adult
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 percutaneous coronary intervention (PCI) is planned (ACC/AHA [Amsterdam 2014]; ACCF/AHA/SCAI [Levine 2011]; ACCF/AHA [O'Gara, 2013]; Stone 2006; Stone 2008). 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, <30 to 45 minutes), or for significant thrombus burden (Lincoff 2019).
Non-ST elevation acute coronary syndromes: Note: Begin after diagnostic coronary angiography, just before PCI (Giugliano 2009; Stone 2007). IV: Bolus of 180 mcg/kg (maximum: 22.6 mg), followed by a continuous infusion of 2 mcg/kg/minute (maximum: 15 mg/hour); a second bolus of 180 mcg/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 (ACC/AHA [Amsterdam 2014]; ACCF/AHA/SCAI [Levine 2011]; Cutlip 2019b).
ST elevation myocardial infarction (off-label use): Note: Begin after diagnostic coronary angiography, just before PCI (Lincoff 2019). IV: Bolus of 180 mcg/kg (maximum: 22.6 mg), followed by a continuous infusion of 2 mcg/kg/minute (maximum: 15 mg/hour); a second bolus of 180 mcg/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 (ACC/AHA [O’Gara 2013]; ACCF/AHA/SCAI [Levine 2011]; Lincoff 2019).
Percutaneous coronary intervention with or without coronary stenting: Note: Aspirin, a P2Y12 inhibitor (eg, clopidogrel, prasugrel, 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 (ACCF/AHA/SCAI [Levine 2011]; Cutlip 2019a). IV: Bolus of 180 mcg/kg (maximum: 22.6 mg) administered immediately before PCI, followed by a continuous infusion of 2 mcg/kg/minute (maximum: 15 mg/hour); a second bolus of 180 mcg/kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus; may continue infusion for 2 to 24 hours after PCI (Fung 2009).
Note: If CABG is performed, some experts recommend discontinuing eptifibatide ≥2 to 4 hours before surgery (ACC/AHA [Amsterdam 2014]; ACCF/AHA [Hillis 2011]; ACCF/AHA [O'Gara 2013]); pharmacokinetic studies indicate that platelet function is restored ~4 to 8 hours after discontinuation (Tardiff 2001).
Dosing: Geriatric
Refer to adult dosing. No dosing adjustment for the elderly appears to be necessary; adjust carefully to renal function.
Administration
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.
Storage
Vials should be stored refrigerated at 2°C to 8°C (36°F to 46°F). Vials can be kept at room temperature for 2 months, after which they must be discarded. Protect from light until administration. Do not use beyond the expiration date. Discard any unused portion left in the vial.
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
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
Frequency not always defined. Bleeding is the major drug-related adverse effect. Access site is often primary source of bleeding complications. Incidence of bleeding is also related to heparin intensity. Patients weighing <70 kg may have an increased risk of major bleeding.
>10%: Hematologic: & oncologic: Hemorrhage (major: 1% to 11%; minor: 3% to 14%; transfusion required: 2% to 13%)
1% to 10%:
Cardiovascular: Hypotension (≤7%)
Hematologic & oncologic: Thrombocytopenia (1% to 3%; includes acute profound thrombocytopenia, immune-mediated thrombocytopenia)
Local: Injection site reaction
<1%, postmarketing and/or case reports: Anaphylaxis, cerebrovascular accident, gastrointestinal hemorrhage, intracranial hemorrhage, pulmonary hemorrhage
Warnings/Precautions
Concerns related to adverse effects:
- 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. Risk factors for bleeding include older age, a history of bleeding disorders, and concomitant use of drugs that increase the risk of bleeding (thrombolytics, oral anticoagulants, NSAIDs, and/or P2Y12 inhibitors). Patients <70 kg may be at greater risk for major and minor bleeding. Minimize invasive procedures, including arterial and venous punctures, IM injections, and the use of urinary catheters, nasotracheal intubation and nasogastric tubes.
- Hypersensitivity: Hypersensitivity reactions have occurred, including anaphylaxis and urticaria.
- Thrombocytopenia: Acute, profound thrombocytopenia (immune-mediated and nonimmune mediated) has occurred and may occur within 24 hours of initiation (Cheema, 2006; Coons, 2005; Nagge, 2003; Rezkalla, 2003; Salengro, 2003). Platelet counts should recover rapidly (within 1-5 days) after discontinuation. Use with extreme caution in patients with platelet counts <100,000/mm3 (contraindicated in the Canadian labeling). If platelet count decreases to <100,000/mm3 during therapy, discontinue eptifibatide and heparin if administered concurrently. Specific management guidelines for GP IIb/IIIa induced thrombocytopenia have been published (Huxtable, 2006; Llevadot, 2000).
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal dysfunction (estimated CrCl <50 mL/minute, using Cockcroft-Gault equation); dosage adjustment required. Use is contraindicated in patients dependent upon hemodialysis.
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.
Other warnings/precautions:
- Sheath removal: Prior to pulling the sheath, heparin should be discontinued for 3 to 4 hours and ACT should be <180 seconds or aPTT <50 seconds. Of note, full dose anticoagulation is no longer used after successful PCI procedures (ACCF/AHA/SCAI [Levine, 2011]). Use standard compression techniques after sheath removal. Monitor the site closely afterwards for further bleeding.
- Surgery: Discontinue ≥2 to 4 hours prior to coronary artery bypass graft surgery (Hillis, 2011).
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 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. 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, and examine urine, stool and emesis for presence of occult or frank blood; gentle care should be provided when removing dressings.
Pregnancy
Pregnancy Risk Factor
B
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies.
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 (chest pain) or mild heart attacks.
- It may be given to you for other reasons. Talk with the doctor.
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 dizziness
- Passing out
- 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.
