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 ::  Chemistry and ph...
 ::  Pharmacodynamics
 ::  Pharmacokinetics
 ::  Formulation
 ::  Dosage
 ::  Adverse reactions
 ::  Contraindications
 ::  Summary
 ::  References

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Year : 2000  |  Volume : 46  |  Issue : 2  |  Page : 155-6

Eptifibatide: in the treatment of acute coronary syndromes.

Department of Pharmacology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai - 400 012, India., India

Correspondence Address:
M S Oak
Department of Pharmacology, Seth G. S. Medical College and K. E. M. Hospital, Parel, Mumbai - 400 012, India.
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Source of Support: None, Conflict of Interest: None

PMID: 0011013490

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Keywords: Coronary Disease, drug therapy,Human, Peptides, pharmacokinetics,pharmacology,therapeutic use,Platelet Aggregation Inhibitors, pharmacokinetics,pharmacology,therapeutic use,Syndrome,

How to cite this article:
Oak M S, Rege N N. Eptifibatide: in the treatment of acute coronary syndromes. J Postgrad Med 2000;46:155

How to cite this URL:
Oak M S, Rege N N. Eptifibatide: in the treatment of acute coronary syndromes. J Postgrad Med [serial online] 2000 [cited 2023 May 28];46:155. Available from:

Formation of a platelet rich white thrombus due to disruption of coronary vascular endothelium is the crucial event in progression of stable angina to acute coronary syndrome (ACS) and complications of percutaneous coronary interventions (PCI).

Atherosclerotic plaque rupture, vascular injury (e.g., from PCI procedures), or denudation of endothelium exposes the subendothelial matrix of the vessel to circulating platelets. Subsequent activation of platelets results in a conformational change in the Glycoprotein (GP) IIb/IIIa present in the platelet membrane thereby activating it’s receptor function for fibrinogen and Von Willebrand factor in the plasma. Fibrinogen and Von Willebrand factor link the GP IIb/IIIa from the adjacent platelets leading to their aggregation and thus thrombus formation. This binding of fibrinogen and Von Willebrand factor to the platelet membrane glycoprotein IIb/ IIIa receptor is the final common pathway by which the activated platelets aggregate to form a platelet rich white thrombus irrespective of initial activating stimulus. Eptifibatide blocks this final common pathway and has been approved as a new drug for ACS by The Drug Controller General of India in August 1999.

  ::   Chemistry and pharmacology Top

Eptifibatide is a synthetic cyclic heptapeptide and has a lysine-glycine-aspartate amino acid sequence within its structure. This sequence is similar to the physiologic arginine-glycine-aspartate sequence in adhesive ligands like von Willebrand’s factor, fibrinogen, etc, which bind to platelet GP IIb/IIIa receptors on activated platelets and cause platelet aggregation. The substitution of lysine for arginine on the binding site in eptifibatide increases its selectivity to the GP IIb/IIIa receptor[1].

  ::   Pharmacodynamics Top

This agent causes selective, reversible and competitive inhibition of binding of fibrinogen, Von Willebrand factor and other adhesive ligands, to resting and active GP IIb/IIIa receptors. As GP IIb/IIIa is confined to platelets and their precursors, the pharmacological action of Eptifibatide is essentially confined to those cells, thus minimising the potential for side effects[1],[2].

Rapid inhibition of platelet aggregation occurs within 15 minutes of Eptifibatide treatment in a dose- and concentration-dependent manner, and at appropriate dosages this inhibition remains sustained for the duration of the drug infusion. Platelet function is restored to normal within 2 to 4 hours after treatment termination[1],[3].

Eptifibatide has been compared in various phase II studies with either placebo or aspirin. It has shown a better profile than the comparators, in reducing incidence of ischaemia, coronary reperfusion with rapid ST-segment recovery and inhibition of platelet aggregation. These findings have been confirmed in two large multi-centric studies: IMPACT II and PERSUIT.

IMPACT II (Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis) was a randomised, double-blind, placebo-controlled multi-centre phase III clinical trial involving patient with ACS scheduled for either elective, urgent, or emergency coronary interventions. In this trial eptifibatide was compared with placebo as an add-on therapy to aspirin (325 mg) and a bolus of 100 U/kg of heparin. Eptifibatide significantly reduced the composite incidence of death, myocardial infarction (MI), and need for urgent revascularisation compared with that for the placebo group. It also reduced the incidence of abrupt vessel closure at 24 hours following PCI. Further, a decreased incidence of the composite end point at 30 days in eptifibatide group compared with placebo suggests a lasting benefit of the effects achieved immediately after angioplasty[4].

PERSUIT (Platelet GP IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy) was a worldwide phase III evaluation of Eptifibatide in 10,948 patients with unstable angina and non-Q-wave MI[3]. All the patients received aspirin, heparin and other adjunct therapies, along with eptifibatide or placebo. At 30 days follow-up, Eptifibatide treatment was found to reduce the incidence of death or MI significantly. Subsequent pharmaco-economic analysis of the data revealed that eptifibatide therapy is cost effective[5].

  ::   Pharmacokinetics Top

Eptifibatide has a short half-life of 1 to 2 hours. Eptifibatide is eliminated by both renal and non-renal mechanisms. Dosage adjustment is not necessary in patients with mild to moderate renal impairment. Patients with unstable angina or non-Q-wave myocardial infarction who have serum creatinine concentrations between 2 and 4 mg/dl should receive the lower dosage i.e. 135-µg/kg intravenous loading dose and 0.5 µg/kg per minute by intravenous infusion. With recommended dosage, peak plasma drug concentration occurs within 5 minutes of injection and steady-state drug concentration is 1.5 - 2.2 µg/ml6.

  ::   Formulation Top

Eptifibatide is available for intravenous (i.v.) administration in the strength of 0.75 mg/ml and 2 mg/ml (10 ml vial) as a clear, colourless, sterile solution. The vial should be stored under refrigeration between 2-80C and protected from light until administration. It is chemically and physically compatible with and may be administered in the same intravenous line as alteplase, atropine, dobutamine, heparin, lidocaine, meperidine, metoprolol, midazolam, morphine, nitroglycerin, or verapamil. However, it is chemically/physically incompatible with furosemide, and these drugs should not be administered through the same i.v. line[6].

  ::   Dosage Top

Based upon the results of various clinical trials the recommended dosage for Eptifibatide for patients with acute coronary syndromes (who are also receiving aspirin and heparin) is 180 µg/kg given as an i.v. loading dose over 1-2 minutes as soon as possible following diagnosis. This is followed by continuous i.v. infusion of 2 µg/kg per minute until hospital discharge or initiation of coronary artery bypass grafting, or for up to 72 hours (96 hours for those undergoing PCI).

Eptifibatide has additive effects on activated clotting time (ACT) in patients receiving heparin and hence the dosage of heparin required to maintain an appropriate ACT during such concomitant therapy may be lower than with heparin monotherapy.

  ::   Adverse reactions Top

Most notable adverse reactions associated with eptifibatide in various clinical trials include: haemorrhagic complications (incidence of major bleeding with eptifibatide was similar to that with placebo in the IMPACT-II study and modestly increased compared with placebo in the PURSUIT study); anaphylaxis (0.16 % in PURSUIT trial); stroke (Incidence similar to placebo in PURSUIT or IMPACT-II study); and hypotention (7% of patients receiving eptifibatide and 6% of those receiving placebo in the PURSUIT study). Thrombocytopenia and need for platelet transfusion (incidence slightly higher than placebo in IMPACT II and PERSUIT study)[3],[4].

  ::   Contraindications Top

In general same contraindications apply to the use of epitfibatide as those for thrombolytics in acute myocardial infarction.

  ::   Summary Top

Ability of eptifibatide to interfere with the final common pathway of platelet aggregation makes it superior to other available antiplatelet agents. Its pharmacokinetic profile (rapid onset of action and quick reversibility after termination of infusion) is an added advantage. Further, it does not induce antibody formation like that of abciximab - the monoclonal antibody against GP IIb/IIIa receptor[7]. Eptifibatide does not worsen the incidence of haemorrhagic complications of anti-platelet therapy. As an add-on therapy to heparin, it has been shown to be superior to the placebo in various clinical trials involving patients with unstable angina, acute MI and patients with acute coronary events undergoing a percutaneous intervention.

 :: References Top

1.   Back to cited text no. 1    
2.Scarborough R M. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Am Heart J 1999; 138: 1093-1104  Back to cited text no. 2    
3.Lefkovits J, Plow EF, Topol EJ. Mechanisms of Disease: Platelet Glycoprotein IIb/IIIa Receptors in Cardiovascular Medicine. N Engl J Med 1995; 332:1553   Back to cited text no. 3    
4.Harrington RA, on behalf of the PURSUIT Trial Investigators. Inhibition of Platelet Glycoprotein IIb/IIIa with Eptifibatide in Patients with Acute Coronary Syndromes. N Engl J Med 1998; 339:436-43.  Back to cited text no. 4    
5.The IMPACT-II Investigators. Lancet 1997; 349:1422-1428  Back to cited text no. 5    
6.Mark DB, Harrington RA, Lincoff AM. Cost-effectiveness of platelet glycoprotein IIb/IIIa inhibition with eptifibatide in patients with non-ST-elevation acute coronary syndromes. Circulation 2000; 101:366-371  Back to cited text no. 6    
7.Medscape Drug Info with First Data Bank and AHSP. [Accessed on May 20, 2000]  Back to cited text no. 7    
8.Lorenz TJ, Macdonald F, Kitt MM. Clin Ther 1999; 21:128-137.  Back to cited text no. 8    


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