Acute coronary syndrome:
Note: Routine antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI) includes oral antiplatelet therapy (eg, aspirin plus a P2Y12 inhibitor) and an IV anticoagulant (eg, heparin or bivalirudin). A glycoprotein 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 (eg, significant thrombus burden) (Ref).
Non-ST elevation acute coronary syndromes: IV: Bolus of 180 mcg/kg (maximum: 22.6 mg) beginning after diagnostic coronary angiography, just 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; continue infusion for up to 18 to 24 hours after PCI (Ref).
ST elevation myocardial infarction (off-label use): IV: Bolus of 180 mcg/kg (maximum: 22.6 mg) beginning after diagnostic coronary angiography, just 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; continue infusion for up to 18 to 24 hours after PCI (Ref).
Percutaneous coronary intervention:
Note: Routine antithrombotic therapy for patients undergoing percutaneous coronary intervention (PCI) includes oral antiplatelet therapy (eg, aspirin plus a P2Y12 inhibitor) and an IV anticoagulant (eg, heparin or bivalirudin). A glycoprotein IIb/IIIa inhibitor is not routinely used due to limited benefit on ischemic outcomes and more bleeding complications (Ref).
IV: Bolus of 180 mcg/kg (maximum bolus: 22.6 mg) beginning after diagnostic coronary angiography, just 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 administer continuous infusion for up to 18 to 24 hours after PCI or until hospital discharge, whichever comes first; alternatively, some administer the continuous infusion for only <2 hours after PCI (Ref).
Note: If coronary artery bypass graft surgery is performed, discontinue eptifibatide ≥4 hours before surgery (Ref); pharmacokinetic studies indicate that platelet function is restored ~4 to 8 hours after discontinuation (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: The Cockcroft-Gault equation using actual body weight should be used to estimate renal function.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: IV: Bolus of 180 mcg/kg (maximum: 22.6 mg) beginning after diagnostic coronary angiography, just before percutaneous coronary intervention (PCI), followed by a continuous infusion of 1 mcg/kg/minute (maximum: 7.5 mg/hour); a second bolus of 180 mcg/kg (maximum: 22.6 mg) should be administered 10 minutes after the first bolus; continue infusion for up to 18 to 24 hours after PCI.
End-stage renal disease (ie, dialysis dependent): Use is contraindicated.
Hemodialysis: Dialyzable: Yes; ~73 to 83% removed after 1 hour (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Refer to adult dosing. No dosing adjustment for the elderly appears to be necessary; adjust carefully to renal function.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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
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
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US 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
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.
Other warnings/precautions:
• Sheath removal: Prior to pulling the sheath after percutaneous coronary intervention (PCI), 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. Use standard compression techniques after sheath removal. Monitor the site closely afterwards for further bleeding.
• Surgery: Discontinue ≥4 hours prior to coronary artery bypass graft surgery (ACC/AHA [Lawton 2022]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Integrilin: 75 mg/100 mL (100 mL [DSC]); 20 mg/10 mL (10 mL [DSC]); 200 mg/100 mL (100 mL [DSC])
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)
Yes
Solution (Eptifibatide Intravenous)
20 mg/10 mL (per mL): $3.60 - $18.78
75 mg/100 mL (per mL): $1.08 - $5.88
200 mg/100 mL (per mL): $4.80 - $16.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Integrilin: 75 mg/100 mL ([DSC]); 20 mg/10 mL ([DSC])
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.
Percutaneous coronary intervention: Treatment of patients undergoing percutaneous coronary intervention, including those undergoing intracoronary stenting.
Non-ST elevation acute coronary syndromes: Treatment of patients with unstable angina or non–ST-segment elevation myocardial infarction, primarily for patients undergoing percutaneous coronary intervention.
ST-elevation myocardial infarction
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: 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. Risk C: 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. Risk D: Consider therapy modification
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: 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. Risk C: Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: 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. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: 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. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: 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. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: 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. Risk C: Monitor therapy
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Information related to eptifibatide use in pregnancy is limited (Al-Aqeedi 2008; Bauer 2012; Serna Candel 2019). Myocardial infarction is a medical emergency; maternal treatment should not be withheld because of fears of teratogenicity.
It is not known if eptifibatide is present in breast milk.
If present in breast milk, eptifibatide is expected to be destroyed in the infant GI tract and not be orally absorbed via breastfeeding.
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.
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.
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: Platelet function restored ~4 to 8 hours following discontinuation (Tardiff, 2001)
Protein binding: ~25%
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
Altered kidney function: 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).
Older adult: Higher plasma levels and lower total body clearance.
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