Integrilin (Schering Plough)
10 mL vial containing 2 mg/mL
100 mL vial containing 0.75 mg/mL
Approved indications: unstable angina, myocardial infarction, intracoronary stenting
Australian Medicines Handbook section 7.2.1

Eptifibatide is the latest of several glycoprotein IIb/IIIa receptor antagonists such as tirofiban and abciximab, to be marketed in Australia. These drugs work in acute coronary syndromes by inhibiting platelet aggregation.1

Patients with unstable angina or non-Q wave myocardial infarction are given an intravenous bolus of eptifibatide. This is followed by an infusion which continues, for up to 72 hours, until the patient has a coronary bypass or leaves hospital. In most patients this regimen will inhibit more than 80% of platelet aggregation. The half-life of eptifibatide is 2.5 hours with half of the dose being cleared by the kidney.

The efficacy of eptifibatide was assessed in a study of 10 948 patients with acute cardiac ischaemia. They were given eptifibatide or a placebo, in addition to aspirin and heparin. Eptifibatide significantly reduced the number of patients who died or suffered a myocardial infarction within 30 days.2

Eptifibatide can also be used in patients who require intracoronary stenting. A trial randomised 2064 patients to receive two doses of eptifibatide and an infusion, or a placebo before the non-urgent percutaneous implantation of a stent. The primary end-point of the trial was a composite of death, myocardial infarction, urgent revascularisation and 'bailout glycoprotein IIb/IIIa inhibitor therapy'. This trial was stopped early because of a significant difference in the primary end-point between eptifibatide and placebo (10.5% versus 6.6%).3

Predictably, bleeding is an important adverse effect of eptifibatide. In the pivotal study 11.6% of patients needed a transfusion.2This bleeding most often occurred in patients who require coronary artery bypass grafting and was also a problem for the patients given a placebo. Approximately 9% of the patients given a placebo needed a transfusion.2Common sites for bleeding are the femoral artery access point, the genitourinary system and the gut.

Monitoring the patient includes checking their blood counts within six hours of starting treatment and then at least once a day. The activated clotting time should be measured in patients having percutaneous coronary interventions.

Although the effect of eptifibatide in acute ischaemia is statistically significant the absolute reduction is only 1.5%. (Eptifibatide reduces deaths and myocardial infarctions from 15.7% to 14.2%.2) In the stenting study the overall benefit was accounted for by a reduction in myocardial infarctions. The difference in mortality between eptifibatide and placebo was not significant. The benefits of eptifibatide need to be balanced against the cost of managing the extra haemorrhages it causes.

References

  1. Lefkovits J. Recent advances in antiplatelet therapy. Aust Prescr 1996;19:98-101.
  2. 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.
  3. The ESPRIT investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037-44.

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.