The eptifibatide dosing regimen used in the ESPRIT study included two 180 µg/kg bolus doses given ten minutes apart combined with a continuous 2.0 µg/kg/min infusion.

When administered alone, eptifibatide has no measurable effect on prothrombin time (PT) or activated partial thromboplastin time (aPTT). (See also PRECAUTIONS ).

There were no important differences between men and women or between age groups in the pharmacodynamic properties of eptifibatide. Differences among ethnic groups have not been assessed.

Pharmacokinetics

The pharmacokinetics of eptifibatide are linear and dose-proportional for bolus doses ranging from 90 to 250 µg/kg and infusion rates from 0.5 to 3.0 µg/kg/min. Plasma elimination half-life is approximately 2.5 hours. Administration of a single 180 µg/kg bolus combined with an infusion produces an early peak level, followed by a small decline prior to attaining steady state (within 4-6 hours). This decline can be prevented by administering a second 180 µg/kg bolus ten minutes after the first. The extent of eptifibatide binding to human plasma protein is about 25%. Clearance in patients with coronary artery disease is about 55-58 mL/kg/h. In healthy subjects, renal clearance accounts for approximately 50% of total body clearance, with the majority of the drug excreted in the urine as eptifibatide, deamidated eptifibatide, and other, more polar metabolites. No major metabolites have been detected in human plasma. In patients with moderate to severe renal insufficiency (creatinine clearance <50 mL/min using the Cockroft-Gault equation), the clearance of eptifibatide is reduced by approximately 50% and steady-state plasma levels approximately doubled (see WARNINGS, DOSAGE AND ADMINISTRATION).

Special Populations

Patients in clinical studies were older (range 20 to 94 years) than those in the clinical pharmacology studies. Elderly patients with coronary artery disease demonstrated higher plasma levels and lower total body clearance of eptifibatide when given the same dose as younger patients. Limited data are available on lighter weight (<50 kg) patients over 75 years of age.

No studies have been conducted in patients with hepatic impairment.

Males and females have not demonstrated any clinically significant differences in the pharmacokinetics of eptifibatide.

CLINICAL STUDIES

Eptifibatide was studied in three placebo-controlled, randomized studies. PURSUIT evaluated patients with acute coronary syndromes: unstable angina (UA) or non-ST-segment myocardial infarction (NSTEMI). Two other studies, ESPRIT and IMPACT II, evaluated patients about to undergo a percutaneous coronary intervention (PCI). Patients underwent primarily balloon angioplasty in IMPACT II and intracoronary stent placement, with or without angioplasty, in ESPRIT.

Non-ST-segment Elevation Acute Coronary Syndrome

Non-ST-segment elevation acute coronary syndrome is defined as prolonged (≥10 minutes) symptoms of cardiac ischemia within the previous 24 hours associated with either ST-segment changes (elevation between 0.6 mm and 1 mm or depression >0.5 mm), T-wave inversion (>1 mm), or positive CK-MB. This definition includes "unstable angina" and "NSTEMI" but excludes myocardial infarction that is associated with Q waves or greater degrees of ST-segment elevation.

PURSUIT (Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using INTEGRILIN Therapy)

PURSUIT was a 726-center, 27-country, double-blind, randomized, placebo-controlled study in 10,948 patients presenting with UA or NSTEMI. Patients could be enrolled only if they had experienced cardiac ischemia at rest (≥10 minutes) within the previous 24 hours and had either ST-segment changes (elevations between 0.6 mm and 1 mm or depression >0.5 mm), T-wave inversion (>1 mm), or increased CK-MB. Important exclusion criteria included a history of bleeding diathesis, evidence of abnormal bleeding within the previous 30 days, uncontrolled hypertension, major surgery within the previous 6 weeks, stroke within the previous 30 days, any history of hemorrhagic stroke, serum creatinine >2.0 mg/dL, dependency on renal dialysis, or platelet count <100,000/mm³.

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