honestly [70:<50 mL/minute, 180 mcg/kg by IV injection as soon as possible following diagnosis, followed by IV infusion of 1 mcg/kg per minute. 1 Acute Ischemic Complications of PCI In patients with Cl cr> <50 mL/minute, 180 mcg/kg by IV injection immediately before initiation of PCI, followed by IV infusion of 1 mcg/kg per minute and a second IV injection of 180 mcg/kg 10 minutes after the first IV injection. 1 Geriatric Patients No dosage adjustment was made for geriatric patients in clinical trials. 1 (See Geriatric Use under Cautions.) Cautions for Eptifibatide Contraindications History of bleeding diathesis 1 10 13 or active abnormal bleeding within previous 30 days. 1 10 12 13 Severe uncontrolled hypertension (SBP >200 mm Hg or DBP >110 mm Hg with antihypertensive therapy). 1 10 13 Recent (within 6 weeks) major surgery. 1 10 12 13 History of stroke within 30 days or any history of hemorrhagic stroke. 1 10 12 13 Current or planned therapy with another GP IIb/IIIa-receptor inhibitor. 1 Patients undergoing renal dialysis. 1 Known hypersensitivity to eptifibatide or any ingredient in the formulation. 1 Warnings/Precautions Warnings Bleeding Risk of major bleeding (e.g., intracranial hemorrhage, GU or GI bleeding, bleeding at femoral vascular access site) 1 8 17 71 85 117 and minor bleeding (e.g., spontaneous gross hematuria, spontaneous hematemesis); 1 8 17 72 85 may require blood or platelet transfusions. 1 10 117 (See Bleeding Precautions and see Laboratory Monitoring under Cautions.) Patients weighing> <70 kg at increased risk of major bleeding. 1 If bleeding cannot be controlled by pressure, discontinue eptifibatide and concomitant heparin immediately. 1 Use not recommended in patients with hematocrit> <30%. 8 72 Thrombocytopenia Thrombocytopenia reported. 110 111 Severe thrombocytopenia (platelet count> <20,000/mm 3 ) reported less frequently than with abciximab. 8 26 40 55 72 93 99 111 Determine platelet counts prior to treatment and periodically (e.g., daily) 72 during concomitant eptifibatide and heparin therapy. 8 72 88 Consider possibility of heparin-induced thrombocytopenia in patients receiving concomitant heparin therapy. 29 55 93 107 111 If platelet count decreases to> <100,000/mm 3 , discontinue eptifibatide and heparin and initiate appropriate treatment and monitoring. 1 Consider platelet transfusions for management of severe thrombocytopenia. 55 93 106 111 112 No clinical experience with eptifibatide in patients with platelet counts> <100,000/mm 3 . 1 Sensitivity Reactions Hypersensitivity Reactions Anaphylaxis reported. 1 Major Toxicities General Precautions Bleeding Precautions To reduce risk of bleeding, adhere to strict anticoagulation guidelines; use a short course of low-dose, weight-adjusted heparin; avoid vascular and other trauma; carefully manage vascular (e.g., femoral artery) access site; and monitor all potential bleeding sites during and following treatment. 1 26 29 43 52 97 107 109 Manufacturer recommends that concomitant thrombolytic therapy be used with caution. 1 In patients undergoing PCI, use caution in the placement, maintenance, and removal of vascular access sheath. 1 26 44 52 When inserting sheath, puncture only anterior wall of femoral artery; avoid Seldinger (through and through) technique. 8 26 72 Observe appropriate precautions while sheath is in place (e.g., complete bed rest, elevation of head 30 , restrain limb in which sheath is inserted, frequent monitoring of vascular access site and distal pulse in the involved limb). 26 27 72 Following PCI, consider early sheath removal (during eptifibatide IV infusion). 1 Prior to removal of sheath, discontinue heparin for 3 4 hours and allow aPTT to return to> <45 seconds or ACT to> <150 180 seconds. 1 26 27 35 44 Discontinue eptifibatide and heparin and achieve hemostasis (by applying pressure to femoral artery for at least 20 30 minutes after sheath removal 26 27 ) at least 2 4 hours before hospital discharge. 1 Measure and monitor hematomas for enlargement. 8 26 72 To avoid vascular and other trauma, minimize needle punctures (e.g., arterial, IM, IV, lumbar, sub-Q, intradermal), cutdown sites, and use of nasotracheal intubation, nasogastric tubes, urinary catheters, and automatic BP cuffs 26 during and following treatment; 1 8 72 avoid establishment of IV access at noncompressible sites (e.g., subclavian or jugular veins); 1 consider using an indwelling venipuncture device (e.g., heparin lock) for drawing blood; document and monitor vascular puncture sites; and remove dressings gently and carefully. 8 26 72 Laboratory Monitoring Prior to administration, obtain hematocrit or hemoglobin, platelet count, S cr , and PT or aPTT. 1 In patients undergoing PCI, also obtain ACT prior to administration. 1 In patients with unstable angina or non-ST-segment-elevation MI undergoing medical management, target aPTT between 50 70 seconds. 1 In patients undergoing PCI the manufacturer recommends targeting ACT between 200 300 seconds during PCI. 1 Monitor aPTT or ACT prior to arterial sheath removal; do not remove sheath unless aPTT 45 seconds or ACT> <150 180 seconds. 1 26 27 35 44 Specific Populations Pregnancy Category B. 1 Lactation Not known whether eptifibatide is distributed into milk. 1 Use with caution. 1 Pediatric Use Safety and efficacy not established. 1 8 Geriatric Use No substantial differences in efficacy relative to younger adults. 1 However, increased incidence of bleeding complications. 1 Hepatic Impairment Use contraindicated in patients with hepatic disease severe enough to alter synthesis of coagulation factors. 8 Renal Impairment Decreased clearance and increased plasma concentrations in patients with moderate to severe renal impairment (estimated Cl cr> <50 mL/minute); 1 reduced dosage recommended in such patients. 1 (See Renal Impairment under Dosage and Administration.) Use contraindicated in patients undergoing renal dialysis. 1 Common Adverse Effects Bleeding, 1 hypotension. 1 8 43 Interactions for Eptifibatide Specific Drugs Drug Interaction Comments Anticoagulants, oral Potential increased risk of bleeding 1 Use with caution 1 Dipyridamole Potential increased risk of bleeding 1 Use with caution 1 Enoxaparin Pharmacokinetic or pharmacodynamic (e.g., effect on platelet aggregation) interaction unlikely 1 GP IIb/IIIa-receptor inhibitors (abciximab, tirofiban) Possible additive pharmacologic effects 1 4 Avoid concomitant use 1 4 Heparin Possible additive effects on ACT 19 Reduce dosage of heparin to maintain appropriate ACT 19 NSAIAs Potential increased risk of bleeding 1 Use with caution 1 Thrombolytics (e.g., alteplase, streptokinase) Increased risk of bleeding, including that requiring blood transfusions 1 5 34 Use with caution 1 4 34 43 72 Eptifibatide Pharmacokinetics Absorption Bioavailability Peak plasma concentrations achieved within 5 minutes and steady-state concentrations attained within 4 6 hours following IV administration. 1 4 9 41 43 Onset Maximal inhibition of platelet aggregation occurs within 15 minutes following IV administration and is rapidly reversible. 1 8 12 Duration Platelet aggregation usually returns to normal within 4 8 hours after discontinuing therapy. 8 13 31 41 43 Special Populations Steady-state plasma concentrations double in patients with moderate to severe renal impairment (estimated Cl cr> <50 mL/minute). 1 Increased plasma concentrations in geriatric patients. 1 Distribution Extent Not known whether eptifibatide is distributed into breast milk. 1 Plasma Protein Binding Approximately 25% (mainly albumin). 1 8 41 43 Elimination Metabolism Principally metabolized to a less active metabolite; 1 9 41 71 27% of dose is converted in plasma into naturally occurring amino acids. 4 41 Elimination Route Eliminated by renal (40 50% of total body clearance) 1 8 9 71 and nonrenal mechanisms, 9 41 43 71 mainly as parent drug and metabolites. 1 In healthy men, approximately 98, 1.5, and 0.8% of a single dose was recovered in urine, feces, and breath carbon dioxide, respectively. 9 May be removed by hemodialysis. 1 Half-life 2.5 2.8 hours in patients with CAD; 1 8 19 0.83 2.4 hours in healthy individuals. 2 8 42 71 Special Populations Clearance reduced by 50% in patients with moderate to severe renal impairment (estimated Cl cr> <50 mL/minute). 1 Reduced total body clearance in geriatric patients. 1 Stability Storage Parenteral Injection 2 8 C. 1 8 Protect from light. 1 8 May store at room temperature (15 30 C) for 2 months. 1 8 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral No incompatibilities observed with IV administration sets; no compatibility studies performed with polyvinyl chloride (PVC) bags. 1 Solution Compatibility 1 *Infusion may contain up to 60 mEq/L of potassium chloride. 1 Compatible Dextrose 5% and sodium chloride 0.9%* Sodium chloride 0.9%* Drug Compatibility 1 Admixture CompatibilityHID Compatible Alteplase Amiodarone HCl Atropine Bivalirudin Dobutamine HCI Heparin sodium Lidocaine HCI Meperidine HCI Metoprolol tartrate Midazolam HCI Morphine sulfate Nitroglycerin Verapamil HCI Incompatible Furosemide Actions Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa receptors). 1 2 3 4 7 8 16 37 71 Modest effect on hemostatic indices (e.g., bleeding times) and platelet function; normal hemostasis restored more rapidly than with abciximab. 1 2 6 10 17 72 Usually does not affect PT or aPTT when administered as monotherapy. 1 Advice to Patients Risk of serious bleeding or hemorrhage. 1 Importance of close laboratory monitoring. 1 Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. 1 Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. 1 Importance of advising patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. Eptifibatide Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral Injection, for IV Use 2 mg/mL (20 mg) Integrilin Schering 0.75 mg/mL (75 mg) Integrilin Schering AHFS DI Essentials. Copyright 2017, Selected Revisions September 18, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. † Use is not currently included in the labeling approved by the US Food and Drug Administration. References 1. Schering. Integrilin (eptifibatide) injection prescribing information. Kenilworth, NJ; 2007 Mar. 2. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol . 1997; 80(Suppl 4A):11b-20b. 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