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    GP IIb/IIIa (glycoprotein) Antagonist Platelet Aggregation Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    Intravenous platelet glycoprotein IIb/IIIa inhibitor
    Used to reduce complications associated with percutaneous coronary intervention (PCI)
    Dose reduction required for CrCl < 50 mL/minute

    COMMON BRAND NAMES

    Integrilin

    HOW SUPPLIED

    Eptifibatide/Integrilin Intravenous Inj Sol: 0.75mg, 1mL, 2mg

    DOSAGE & INDICATIONS

    For the adjunctive treatment of patients undergoing percutaneous coronary intervention (PCI), including those undergoing coronary stenting, to prevent cardiac ischemic complications (e.g., myocardial infarction prophylaxis).
    Intravenous dosage
    Adults

    180 mcg/kg IV bolus (Max: 22.6 mg) administered immediately before PCI, followed by 2 mcg/kg/minute continuous IV infusion, not to exceed 15 mg/hr for patients weighing > 121 kg. Administer a second 180 mcg/kg IV bolus 10 minutes after the first IV bolus. The infusion should be continued until hospital discharge, or for up to 18—24 hours, whichever comes first. A minimum of 12 hours of therapy is recommended. Eptifibatide should be used in combination with aspirin (unless contraindicated) and heparin. Administer aspirin 160—325 mg PO 1—24 hours prior to PCI and daily thereafter. Heparin should be dosed to maintain a target ACT of 200—300 seconds. Administer a heparin 60 unit/kg IV bolus initially in patients not treated with heparin within 6 hours prior to PCI. Additional heparin boluses may be administered during PCI to maintain target ACT. Heparin administration after PCI is discouraged. Discontinue eptifibatide in patients who require thrombolytic therapy.If CABG surgery is planned, discontinue eptifibatide at least 2—4 hours prior to surgery.

    For the treatment of patients with acute coronary syndrome (unstable angina or acute myocardial infarction, NSTEMI), including patients who are to be managed medically, and for those undergoing percutaneous coronary intervention (PCI).
    Intravenous dosage
    Adults

    180 mcg/kg IV bolus (Max: 22.6 mg) as soon as possible following diagnosis, followed by 2 mcg/kg/minute continuous IV infusion, not to exceed 15 mg/hour for patients weighing > 121 kg. The infusion should be continued until hospital discharge, initiation of CABG surgery, or for up to 72 hours. If a patient is to undergo PCI, the infusion should be continued until hospital discharge, or for an additional 18—24 hours after the procedure, whichever comes first, allowing for up to 96 hours of therapy. Eptifibatide should be used in combination with aspirin (unless contraindicated) and heparin. Administer aspirin 160—325 mg PO daily. If the patient is to be managed medically, dose heparin to maintain a target aPTT of 50—70 seconds. If weight is >= 70 kg, administer a heparin 5000 unit IV bolus followed by a heparin continuous IV infusion of 1000 units/hour. If weight is < 70 kg, administer a heparin 60 unit/kg IV bolus followed by a heparin continuous IV infusion of 12 units/kg/hour. If the patient is to undergo PCI, dose heparin to maintain a target ACT of 200—300 seconds. If heparin is initiated prior to PCI, additional heparin boluses may be required during PCI to maintain target ACT. Heparin administration after PCI is discouraged. Discontinue eptifibatide in patients who require thrombolytic therapy. If CABG surgery is planned, discontinue eptifibatide at least 2—4 hours prior to surgery. Clinical practice guidelines support GP IIb/IIIa inhibitors at the time of PCI for patients with UA and NSTEMI with intermediate/high-risk features (e.g., positive troponin) treated with early invasive strategy and dual antiplatelet therapy; a GP IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy, and double-bolus eptifibatide (a second 180 mcg/kg IV bolus [Max: 22.6 mg] 10 minutes after first IV bolus) is a preferred option. This regimen is also recommended at the time of PCI for UA/NSTEMI patients with high-risk features (e.g., elevated troponin) who are receiving unfractionated heparin (UFH), not treated with bivalirudin, not adequately pretreated with ticagrelor, and regardless of clopidogrel pretreatment.

    For the treatment of patients with acute myocardial infarction, STEMI† undergoing percutaneous coronary intervention (PCI).
    Intravenous dosage
    Adults

    180 mcg/kg IV bolus (Max: 22.6 mg) administered immediately before PCI, followed by 2 mcg/kg/minute continuous IV infusion, not to exceed 15 mg/hour for patients weighing > 121 kg. Administer a second 180 mcg/kg IV bolus 10 minutes after the first IV bolus. The infusion should be continued until hospital discharge, or for up to 18—24 hours, whichever comes first. A minimum of 12 hours of therapy is recommended. Eptifibatide should be used in combination with aspirin (unless contraindicated) and heparin. Administer aspirin 160—325 mg PO 1—24 hours prior to PCI and daily thereafter. Heparin should be dosed to maintain a target ACT of 200—300 seconds. Administer a heparin 60 unit/kg IV bolus initially in patients not treated with heparin within 6 hours prior to PCI. Additional heparin boluses may be administered during PCI to maintain target ACT. Heparin administration after PCI is discouraged. Discontinue eptifibatide in patients who require thrombolytic therapy.Clinical practice guidelines support the adjunctive use of GP IIb/IIIa inhibitors at the time of primary PCI in select patients with STEMI (i.e., large thrombus burden or inadequate P2Y12 receptor antagonist loading) who are receiving unfractionated heparin (UFH) and treated with or without clopidogrel or stenting. If coronary artery bypass graft (CABG) surgery is planned, discontinue eptifibatide at least 2—4 hours prior to surgery.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    180 mcg/kg IV bolus (max: 22.6 mg for patients weighing >121 kg); 2 mcg/kg/min continuous IV infusion (max: 15 mg/hour for patients weighing > 121 kg). Refer to prescribing information for bolus volume and infusion rate to be administered based on patient weight, dose prescribed, and infusion concentration.

    Geriatric

    180 mcg/kg IV bolus (max: 22.6 mg for patients weighing >121 kg); 2 mcg/kg/min continuous IV infusion (max: 15 mg/hour for patients weighing > 121 kg). Refer to prescribing information for bolus volume and infusion rate to be administered based on patient weight, dose prescribed, and infusion concentration.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    CrCl >= 50 mL/min: No adjustment is needed.
    CrCl < 50 mL/min: Reduce the maintenance infusion dosage to 1 mcg/kg/min IV (maximum infusion rate of 7.5 mg/hour IV). No dosage adjustment is needed for the recommended IV bolus regimen.
    CrCl < 10 mL/min: Use is contraindicated in patients with dependency on renal dialysis.
     
    Intermittent hemodialysis
    Eptifibatide is contraindicated in patients with dependency on renal dialysis. In vitro studies indicate that eptifibatide may be cleared from plasma by dialysis (in vivo data not available). There has been no clinical experience in patients dependent on dialysis.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration.

    Intravenous Administration

    Eptifibatide is administered intravenously.
    NOTE: Eptifibatide is incompatible with intravenous furosemide; therefore, these medications should be given in separate IV lines.
     
    Intravenous bolus injection:
    Withdraw bolus dose of eptifibatide from the 10 ml vial into a syringe.
    Administer bolus dose IV over 1—2 minutes.
     
    Continuous IV infusion:
    NOTE: Eptifibatide is available in 100-mL vials containing either 0.75 mg/mL or 2 mg/mL. Refer to the prescribing information for infusion volume to be administered based on patient weight, dose prescribed, and concentration of vial.
    Eptifibatide may be administered in the same IV line with NS or D5NS. With either vehicle, the infusion may contain up to 60 mEq/L of potassium chloride. No incompatibilities have been observed with intravenous administration sets.
    Initiate the continuous infusion immediately following bolus dose administration.
    Using an IV infusion pump, eptifibatide should be administered undiluted directly from the 100 mL vial. The 100 mL vial should be spiked with a vented infusion set.

    STORAGE

    Integrilin:
    - May be stored at temperatures up to 77 degrees F if used within 2 months
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Bleeding, coagulopathy, hypertension, intramuscular injections, stroke, surgery, trauma, venipuncture

    Inhibition of platelet aggregation by eptifibatide increases the risk of bleeding, especially in patients with predisposing conditions. Eptifibatide is contraindicated in patients with any of the following: any coagulopathy or bleeding diathesis, severe uncontrolled hypertension (SBP > 200 mmHg or DBP > 110 mmHg), recent (within 6 weeks) major surgery or trauma, history of stroke within 30 days or any history of hemorrhagic stroke, or any evidence of active abnormal bleeding within the previous 30 days. If serious bleeding occurs that cannot be controlled with pressure, eptifibatide and any concomitant heparin should be discontinued. The risk of bleeding with eptifibatide in the setting of PCI can be reduced if the following precautions are taken: avoidance of venous sheath placement, discontinuation of heparin immediately upon completion of the procedure, early femoral arterial sheath removal (i.e., within 6 hours of the intervention if the aPTT < 45 seconds or the clotting time < 150 seconds and heparin has been discontinued for at least 3—4 hours) followed by at least 30 minutes of pressure to the femoral artery, careful patient and access site management, weight-adjustment of the eptifibatide infusion dose, and avoidance of excessive activated clotting times by limiting the heparin dose. Venipuncture, arterial puncture, intramuscular injections, use of urinary catheters, nasogastric tubes, and nasotracheal intubation should be minimized. When obtaining IV access, noncompressible sites (e.g., subclavian or jugular veins) should be avoided. Based on data from studies of abciximab, patients who undergo PCI should be maintained on complete bed rest (for 6—8 hours following sheath removal or discontinuation of the GP IIb/IIIa receptor antagonist, or 4 hours following discontinuation of heparin, whichever is later) with the head of the bed <= 30 degrees and the affected limb restrained in a straight position.

    Anticoagulant therapy, thrombolytic therapy

    Bleeding risk may be increased in patients receiving eptifibatide concomitantly with heparin, other anticoagulant therapy, or thrombolytics. In clinical trials, most patients received concomitant aspirin and heparin during eptifibatide therapy. In patients receiving thrombolytic therapy, the risk of major bleeding due to concomitant use of eptifibatide should be weighed against the anticipated benefits. If serious bleeding occurs that cannot be controlled with pressure, eptifibatide and any concomitant heparin should be discontinued.

    Dialysis, renal disease, renal failure, renal impairment

    In patients with renal disease, renal function should be assessed prior to eptifibatide therapy. Eptifibatide should not be used in patients with renal failure and is contraindicated in patients with dependency on renal dialysis; there has been no clinical experience with the use of eptifibatide in patients dependent on dialysis. In patients with significant renal impairment associated with a CrCl < 50 mL/min (or serum creatinine >= 2 mg/dL, if estimated CrCl is not available), the dose of eptifibatide should be reduced. The total drug clearance of eptifibatide is reduced by 50% in patients with CrCl < 50 mL/min.

    Geriatric

    Geriatric patients may be at increased risk for bleeding while receiving eptifibatide. In the PURSUIT and IMPACT II trials, patients up to 94 years of age were enrolled. The incidence of bleeding was higher in the elderly in both placebo and eptifibatide groups, and the incremental risk of eptifibatide-associated bleeding was greater in the older patients. No dose adjustment was made for elderly patients, but patients over 75 years of age who weighed < 50 kg were not enrolled in the PURSUIT study because of concern about a potential increased bleeding risk.

    Thrombocytopenia

    If a patient with low platelet counts is receiving eptifibatide, their platelet count should be monitored closely. Eptifibatide should not be used in patients with profound thrombocytopenia (i.e., platelet count < 100,000/mm3). If a patient experiences a confirmed decrease in platelet count to < 100,000/mm3 during eptifibatide therapy, eptifibatide and any concomitant heparin should be discontinued. Platelet transfusions should be considered if the platelet count drops below 50,000 cells/mm3.

    Pregnancy

    Eptifibatide is classified as FDA pregnancy category B. Use eptifibatide during pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women with eptifibatide. Eptifibatide use in pregnancy has been described in limited case reports. A 31-year-old pregnant woman at 37 weeks gestation received eptifibatide for 7 days for the peripartum management of her dual antiplatelet therapy after bare metal stent insertion for acute myocardial infarction at 32 weeks gestation. Eptifibatide was discontinued at labor induction, and epidural anesthesia was initiated 12 hours after stopping eptifibatide. The patient had an uneventful vaginal delivery after 12 hours of neuraxial analgesia, and the estimated blood loss was 500 mL. In another case, eptifibatide was used in a 44-year-old pregnant woman at 8 weeks gestation with intracoronary stent placement for acute myocardial infarction. She received eptifibatide for 24 hours before being transitioned to clopidogrel and aspirin. At 36 weeks gestation, the woman delivered a healthy infant via uneventful caesarian section. Teratology studies performed in pregnant rats and rabbits given eptifibatide by continuous intravenous infusion at about 4 times the recommended maximum human dose on a body surface area basis revealed no evidence of harm to the fetus.[30141] [63973] [63974]

    Breast-feeding

    It is not known whether eptifibatide is excreted in human milk. Because many drugs are excreted in human milk, use caution when administering eptifibatide to a breast-feeding woman.[30141]

    ADVERSE REACTIONS

    Severe

    stroke / Early / 0.5-0.7
    anaphylactic shock / Rapid / 0.2-0.2
    anaphylactoid reactions / Rapid / 0.2-0.2
    hematemesis / Delayed / Incidence not known
    retroperitoneal bleeding / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known

    Moderate

    bleeding / Early / 1.3-14.2
    hypotension / Rapid / 7.0-7.0
    thrombocytopenia / Delayed / 1.2-1.2
    platelet dysfunction / Delayed / Incidence not known
    hematuria / Delayed / Incidence not known
    antibody formation / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of platelet inhibitors with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors.
    ADP receptor antagonists: (Moderate) Concomitant use of platelet glycoprotein IIb/IIIa inhibitors (i.e., abciximab, eptifibatide, or tirofiban) with an ADP receptor antagonist (i.e., clopidogrel, prasugrel, ticagrelor, or ticlopidine) may be associated with an increased risk of bleeding.
    Altretamine: (Moderate) An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as altretamine.
    Aminolevulinic Acid: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
    Antimetabolites: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antimetabolites.
    Antithrombin III: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Antithymocyte Globulin: (Moderate) An increased risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia, such as antithymocyte globulin. Platelet inhibitors should be used cautiously in patients with thrombocytopenia following the administration of antithymocyte globulin or other drugs that cause significant thrombocytopenia due to the increased risk of bleeding.
    Apixaban: (Major) The concomitant use of apixaban and platelet inhibitors (e.g, aspirin) may increase the risk of bleeding. In the ARISTOTLE trial (comparative trial of apixaban and warfarin in patients with nonvalvular atrial fibrillation), concomitant use of aspirin increased the bleeding risk of apixaban from 1.8%/year to 3.4%/year. If given concomitantly, patients should be educated about the signs and symptoms of bleeding and be instructed to report them immediately or go to an emergency room.
    Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g., clopidogrel, platelet glycoprotein IIb/IIIa inhibitors, ticlopidine, etc.) in combination with argatroban.
    Arsenic Trioxide: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when eptifibatide is used concomitantly with agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Aspirin, ASA: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Carisoprodol: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban. (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Omeprazole: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Oxycodone: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Aspirin, ASA; Pravastatin: (Moderate) Unless contraindicated, aspirin is used in combination with eptifibatide. However, both drugs are associated with bleeding. Monitor for bleeding during concomitant therapy.
    Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and platelet inhibitors are used concomitantly. Coadministration of betrixaban and platelet inhibitors may increase the risk of bleeding.
    Bexarotene: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including bexarotene.
    Bivalirudin: (Moderate) When used as an anticoagulant in patients undergoing percutaneous coronary intervention (PCI), bivalirudin is intended for use with aspirin (300 to 325 mg/day PO) and has been studied only in patients receiving concomitant aspirin. Generally, an additive risk of bleeding may be seen in patients receiving other platelet inhibitors (other than aspirin). In clinical trials in patients undergoing PTCA, patients receiving bivalirudin with heparin, warfarin, or thrombolytics had increased risks of major bleeding events compared to those receiving bivalirudin alone. According to the manufacturer, the safety and effectiveness of bivalirudin have not been established when used in conjunction with platelet inhibitors other than aspirin. However, bivalirudin has been safely used as an alternative to heparin in combination with provisional use of platelet glycoprotein IIb/IIIa inhibitors during angioplasty (REPLACE-2). In addition, two major clinical trials have evaluated the use of bivalirudin in patients receiving streptokinase following acute myocardial infarction (HERO-1, HERO-2). Based on the these trials, bivalirudin may be considered an alternative to heparin therapy for use in combination with streptokinase for ST-elevation MI. Bivalirudin has not been sufficiently studied in combination with other more specific thrombolytics.
    Chlorambucil: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as chlorambucil.
    Cilostazol: (Moderate) Because cilostazol is a platelet aggregation inhibitor, a potential additive risk for bleeding exists if cilostazol is given with other agent that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
    Cladribine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Clofarabine: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking platelet inhibitors is advised. The efficacy and safety of administering injectable collagenase to a patient taking a platelet inhibitor within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
    Dabigatran: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Dalteparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Danaparoid: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
    Dasatinib: (Moderate) Due to the thrombocytopenic and possible platelet inhibiting effects of dasatinib, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Defibrotide: (Severe) Coadministration of defibrotide with antithrombotic agents like platelet inhibitors is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
    Denileukin Diftitox: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as denileukin difitox.
    Desirudin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
    Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
    Drotrecogin Alfa: (Major) Treatment with drotrecogin alfa should be carefully considered in patients who are receiving or have received any platelet inhibitors within 7 days. These patients are at increased risk of bleeding during drotrecogin alfa therapy.
    Duloxetine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
    Edoxaban: (Major) Coadministration of edoxaban and platelet inhibitors should be avoided due to an increased risk of bleeding during concurrent use. Occasionally, short-term coadministration may be necessary in patients transitioning to and from edoxaban. Long-term coadminstration is not recommended. Promptly evaluate any signs or symptoms of blood loss in patients on concomitant therapy.
    Enoxaparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Estramustine: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as estramustine.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
    Fludarabine: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Folate analogs: (Moderate) Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Fondaparinux: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Garlic, Allium sativum: (Moderate) Use together with caution. Garlic produces clinically significant antiplatelet effects, and a risk for bleeding may occur if platelet inhibitors are given in combination with garlic.
    Ginger, Zingiber officinale: (Moderate) Ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist so additive bleeding may occur if platelet inhibitors are given in combination with ginger, zingiber officinale.
    Ginkgo, Ginkgo biloba: (Major) Use Ginkgo biloba with caution in patients taking platelet inhibitors, as it can produce clinically-significant antiplatelet effects. A compound found in Ginkgo biloba, ginkgolide-B, may act as a selective antagonist of platelet activating factor (PAF). Although a review of Ginkgo biloba in 1992 stated that no known drug interactions exist, spontaneous hyphema has been reported in an elderly male who began taking Ginkgo while stabilized on daily aspirin. After ginkgo was stopped, no further bleeding was noted despite continuing the aspirin therapy. Other clinical data exist that describe spontaneous subdural hematomas associated with chronic Ginkgo biloba ingestion.
    Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if co administered with aspirin. Caution and careful monitoring of clinical and/or laboratory parameters are warranted with this combination.
    Heparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. In clinical trials with eptifibatide, aspirin and heparin were administered concomitantly. Eptifibatide has been administered with a thrombolytic agent in a small number of patients. In the IMPACT II study, 15 patients received a thrombolytic agent with the 135/0.5 dosing regimen, 2 of whom experienced a major bleed. In the PURSUIT study, 40 patients who received eptifibatide (180 mcg/kg bolus, then 2 mcg/kg/min) also received a thrombolytic agent, 10 of whom experienced a major bleed. In another acute MI study (n=181), eptifibatide (180 mcg/kg bolus, then up to 2 mcg/kg/min for up to 72 hours) was administered concomitantly with streptokinase (1.5 mU over 60 min). At the highest studied infusion rates (1.3 to 2 mcg/kg/min), eptifibatide was associated with an increase in the incidence of bleeding and transfusions compared to the incidence seen with streptokinase alone.
    Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with platelet function such as platelet inhibitors; the risk of bleeding may be increased. If coadministration with platelet inhibitors is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
    Ibrutinib: (Moderate) The concomitant use of ibrutinib and antiplatelet agents such as eptifibatide may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood.
    Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
    Iloprost: (Moderate) When used concurrently with platelet inhibitors, inhaled iloprost may increase the risk of bleeding.
    Imatinib: (Moderate) Due to the thrombocytopenic effects of antineoplastics an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and platelet glycoprotein IIb/IIIa inhibitors due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of platelet glycoprotein IIb/IIIa inhibitors in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
    Intravenous Lipid Emulsions: (Moderate) Because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with other platelet inhibitors. Theoretically, the risk of bleeding may be increased.
    Lepirudin: (Moderate) An additive risk of bleeding may be seen in patients receiving platelet inhibitors (e.g., clopidogrel, platelet glycoprotein IIb/IIIa inhibitors, ticlopidine, etc.) in combination with lepirudin.
    Levomilnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of levomilnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
    Lomustine, CCNU: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as lomustine.
    Mercaptopurine, 6-MP: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Methoxsalen: (Minor) Agents that affect platelet function, such as platelet inhibitors, could decrease the efficacy of methoxsalen when used during photodynamic therapy.
    Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs including increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants or antiplatelets including clopidogrel until data confirming the safety of these drug combinations are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving clopidogrel should be observed for increased bleeding.
    Milnacipran: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of milnacipran and platelet inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) affect platelet activation; therefore, concomitant use may increase the risk of bleeding.
    Mycophenolate: (Moderate) Platelet Inhibitors inhibit platelet aggregation and should be used cautiously in patients with thrombocytopenia, as mycophenolate can also cause thrombocytopenia.
    Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, and prolong bleeding time. If NSAIDs are administered with platelet inhibitors, these pharmacodynamic effects may be increased. The manufacturer of clopidogrel advises that caution be used when used in combination with NSAIDs as an increase in occult GI blood loss occurred when clopidogrel was used concomitantly with naproxen
    Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle.
    Pegaspargase: (Moderate) Due to the risk of bleeding and coagulopathy during pegaspargase therapy, patients should receive other agents that may increase the risk of bleeding (e.g., anticoagulants, NSAIDs, platelet inhibitors, or thrombolytic agents) with caution.
    Pentosan: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Pentostatin: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Pentoxifylline: (Moderate) A potential additive risk for bleeding exists if platelet inhibitors are given in combination with other agents that affect hemostasis such as pentoxifylline.
    Phentermine; Topiramate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
    Photosensitizing agents (topical): (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Photosensitizing agents: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Porfimer: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
    Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Prasterone is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
    Purine analogs: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Rivaroxaban: (Major) Avoid concurrent administration of platelet inhibitors such as eptifibatide with rivaroxaban unless the benefit outweighs the risk of increased bleeding. An increase in bleeding time to 45 minutes was observed in 2 drug interaction studies where another platelet inhibitor and rivaroxaban (15 mg single dose) were coadministered in healthy subjects. In the first study, the increase in bleeding time to 45 minutes was observed in approximately 45% of patients. Approximately 30% of patients in the second study had the event. The change in bleeding time was approximately twice the maximum increase seen with either drug alone. No change in the pharmacokinetic parameters of either drug were noted.
    Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by SSRIs due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving platelet inhibitors. Monitor for signs and symptoms of bleeding.
    Sodium Hyaluronate, Hyaluronic Acid: (Moderate) Increased bruising or bleeding at the injection site may occur when using hyaluronate sodium with platelet inhibitors especially if used within the 3 weeks prior to the procedure.
    Sulfinpyrazone: (Major) Sulfinpyrazone, when used as a uricosuric agent should be avoided when possible with concurrent platelet inhibitors due to potential for additive antiplatelet effects and increased bleeding risk.
    Thioguanine, 6-TG: (Moderate) Due to the thrombocytopenic effects of purine analogs, an additive risk of bleeding may be seen in patients receiving concomitant platelet inhibitors.
    Thrombolytic Agents: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Tinzaparin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
    Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving platelet inhibitors. In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including platelet inhibitors, that may have caused or contributed to these events.
    Topiramate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation.
    Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
    Treprostinil: (Moderate) Monitor patients for signs and symptoms of bleeding if treprostinil is administered with eptifibatide. Treprostinil inhibits platelet aggregation; eptifibatide is a platelet inhibitor. Coadministration increases the risk of bleeding.
    Tretinoin, ATRA: (Moderate) An additive risk of bleeding may occur when platelet inhibitors are used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as tretinoin.
    Venlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with a platelet inhibitor and to promptly report any bleeding events to the practitioner.
    Verteporfin: (Minor) Agents, such as platelet inhibitors, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with salicylates or other platelet inhibitors and to promptly report any bleeding events to the practitioner. Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., aspirin, cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors).
    Vorapaxar: (Moderate) Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as platelet glycoprotein IIb/IIIa inhibitors including abciximab, eptifibatide, and tirofiban.
    Vorinostat: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of eptifibatide and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
    Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cilostazol, clopidogrel, dipyridamole, ticlopidine, platelet glycoprotein IIb/IIIa inhibitors). Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
    Warfarin: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.

    PREGNANCY AND LACTATION

    Pregnancy

    Eptifibatide is classified as FDA pregnancy category B. Use eptifibatide during pregnancy only if clearly needed. There are no adequate and well-controlled studies in pregnant women with eptifibatide. Eptifibatide use in pregnancy has been described in limited case reports. A 31-year-old pregnant woman at 37 weeks gestation received eptifibatide for 7 days for the peripartum management of her dual antiplatelet therapy after bare metal stent insertion for acute myocardial infarction at 32 weeks gestation. Eptifibatide was discontinued at labor induction, and epidural anesthesia was initiated 12 hours after stopping eptifibatide. The patient had an uneventful vaginal delivery after 12 hours of neuraxial analgesia, and the estimated blood loss was 500 mL. In another case, eptifibatide was used in a 44-year-old pregnant woman at 8 weeks gestation with intracoronary stent placement for acute myocardial infarction. She received eptifibatide for 24 hours before being transitioned to clopidogrel and aspirin. At 36 weeks gestation, the woman delivered a healthy infant via uneventful caesarian section. Teratology studies performed in pregnant rats and rabbits given eptifibatide by continuous intravenous infusion at about 4 times the recommended maximum human dose on a body surface area basis revealed no evidence of harm to the fetus.[30141] [63973] [63974]

    It is not known whether eptifibatide is excreted in human milk. Because many drugs are excreted in human milk, use caution when administering eptifibatide to a breast-feeding woman.[30141]

    MECHANISM OF ACTION

    Eptifibatide is a competitive inhibitor of glycoprotein (GP) IIb/IIIa preventing the binding of fibrinogen, von Willebrand factor (vWF), and other adhesive ligands to the GP IIb/IIIa receptor on activated platelets. "Integrins", which are found on virtually all cell types, are a family of adhesion molecules that mediate many physiologic responses. Unlike many of the other integrins, GP IIb/IIIa is platelet specific and is also the most abundant receptor found on activated platelets, with about 50,000 copies/cell. Fibrinogen is the principal ligand to bind to the GP IIb/IIIa receptor. The binding of fibrinogen and, to a lesser extent other ligands such as vWF, to the GP IIb/IIIa receptor results in cross-linking between platelets and is the final common pathway of platelet aggregation, which ultimately leads to thrombus formation. Unlike abciximab and tirofiban, which bind to GP IIb/IIIa via an arginine-glycine-aspartic acid (RGD) sequence, eptifibatide contains the lysine-glycine-aspartic acid (KGD) peptide sequence that is thought to create greater specificity for the GP IIb/IIIa receptor. Unlike abciximab, eptifibatide does not bind to the vitronectin receptor. The clinical relevance of binding to vitronectin is not fully understood. Glycoprotein IIb/IIIa inhibitors can prevent platelet aggregation regardless of the agonist involved; thus, eptifibatide will block thrombin-induced platelet aggregation while aspirin will not. When administered alone, eptifibatide has no effect on PT or aPTT.

    PHARMACOKINETICS

    Eptifibatide is administered intravenously. The pharmacokinetics of eptifibatide are linear and dose-proportional for bolus doses ranging 90—250 mcg/kg and infusion rates from 0.5—3 mcg/kg/min. About 25% of eptifibatide is bound to plasma protein. No major metabolites of eptifibatide have been detected in human plasma. In healthy subjects, renal clearance accounts for about 50% of total body clearance, with the majority of drug excreted in the urine as eptifibatide, deamidated eptifibatide, and other, more polar metabolites. Clearance in patients with coronary artery disease is 55—58 mL/kg/hr. The elimination half-life is about 90—120 minutes.
     
    Eptifibatide inhibits ex vivo platelet aggregation induced by adenosine-diphosphate (ADP) and other agonists in a dose- and concentration-dependent manner. With an IV bolus dose of 135 mcg/kg, 69% inhibition of platelet aggregation is achieved after 15 minutes; a bolus dose of 180 mcg/kg produces 84% inhibition of platelet aggregation after 15 minutes. Continuous infusion rates of 0.5 mcg/kg/min and 2 mcg/kg/min produce 40—50% and > 90% inhibition of platelet aggregation, respectively, at steady state; four hours after infusion discontinuation, < 30% and < 50% inhibition of platelet aggregation, respectively, is observed. Bleeding time prolongation returns to baseline within 6 hours after discontinuation of eptifibatide 0.5 mcg/kg/min. Six hours after discontinuation of eptifibatide 2 mcg/kg/min, bleeding time prolongation is about 1.4 times baseline.