Drug Class Description

Generic Name

Drug Description

Presentation

Indications

INTEGRILIN is intended for use with acetylsalicylic acid and unfractionated heparin.

INTEGRILIN is indicated for the prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction with the last episode of chest pain occurring within 24 hours and with ECG changes and/or elevated cardiac enzymes.

Patients most likely to benefit from INTEGRILIN treatment are those at high risk of developing myocardial infarction within the first 3-4 days after onset of acute angina symptoms including for instance those that are likely to undergo an early PTCA (Percutaneous Transluminal Coronary Angioplasty)

Adult Dosage

This product is for hospital use only, by specialist physicians experienced in the management of acute coronary syndromes.

INTEGRILIN solution for infusion must be used in conjunction with INTEGRILIN solution for injection.

Adults ( 18 years of age) presenting with unstable angina or non-Q-wave myocardial infarction

The recommended dosage is an intravenous bolus of 180 microgram/kg administered as soon as possible following diagnosis, followed by a continuous infusion of 2.0 microgram/kg/min for up to 72 hours, until initiation of coronary artery bypass graft (CABG) surgery, or until discharge from the hospital (whichever occurs first). If Percutaneous Coronary Intervention (PCI) is performed during eptifibatide therapy, continue the infusion for 20-24 hours post-PCI for an overall maximum duration of therapy of 96 hours.

Emergency or semi-elective surgery

If the patient requires emergency or urgent cardiac surgery during the course of eptifibatide therapy, terminate the infusion immediately. If the patient requires semi-elective surgery, stop the eptifibatide infusion at an appropriate time to allow time for platelet function to return towards normal.

Hepatic impairment

Experience in patients with hepatic impairment is very limited. Administer with caution to patients with hepatic impairment in whom coagulation could be affected.

Renal impairment

In patients with moderate renal impairment (creatinine clearance 30 - < 50 ml/min), an intravenous bolus of 180 microgram/kg should be administered followed by a continuous infusion dose of 1.0 microgram/kg/min for the duration of therapy. Experience in patients with more severe renal impairment is limited.

Paediatric use

It is not recommended for use in children and adolescents below 18 years of age, due to a lack of data on safety and efficacy.

Child Dosage

Contra Indications

INTEGRILIN must not be used to treat patients with:

− hypersensitivity to the active substance or to any of the excipients

− evidence of gastrointestinal bleeding, gross genitourinary bleeding or other active abnormal bleeding within the previous 30 days of treatment

− history of stroke within 30 days or any history of haemorrhagic stroke

− known history of intracranial disease (neoplasm, arteriovenous malformation, aneurysm)

− major surgery or severe trauma within past 6 weeks

− a history of bleeding diathesis

− thrombocytopaenia ( < 100,000 cells/mm³)

− prothrombin time > 1.2 times control, or International Normalized Ratio (INR) 2.0

− severe hypertension (systolic blood pressure > 200 mm Hg or diastolic blood pressure > 110 mm Hg on antihypertensive therapy)

− severe renal impairment (creatinine clearance < 30 ml/min) or dependency on renal dialysis;

− clinically significant hepatic impairment

− concomitant or planned administration of another parenteral GP IIb/IIIa inhibitor

Special Precautions

Bleeding

INTEGRILIN is an antithrombotic agent that acts by inhibition of platelet aggregation; therefore the patient must be observed carefully for indications of bleeding during treatment. Women, the elderly and patients with low body weight may have an increased risk of bleeding. Monitor these patients closely with regard to bleeding.

Bleeding is most common at the arterial access site in patients undergoing percutaneous arterial procedures. All potential bleeding sites, e.g., catheter insertion sites; arterial, venous, or needle puncture sites; cutdown sites; gastrointestinal and genitourinary tracts must be observed carefully. Other potential bleeding sites such as central and peripheral nervous system and retroperitoneal sites, must be carefully considered too.

Because INTEGRILIN inhibits platelet aggregation, caution must be employed when it is used with other medicinal products that affect haemostasis, including ticlopidine, clopidogrel, thrombolytics, oral anticoagulants, dextran solutions, adenosine, sulfinpyrazone, prostacyclin, non-steroidal anti-inflammatory agents, or dypyridamole.

There is no experience with INTEGRILIN and low molecular weight heparins.

There is limited therapeutic experience with INTEGRILIN in patients for whom thrombolytic therapy is generally indicated (e.g., acute transmural myocardial infarction with new pathological Q-waves or elevated ST-segments or left bundle branch block in the ECG). Consequently the use of INTEGRILIN is not recommended in these circumstances.

Stop the INTEGRILIN infusion immediately if circumstances arise that necessitate thrombolytic therapy or if the patient must undergo an emergency CABG surgery or requires an intraortic balloon pump.

If serious bleeding occurs that is not controllable with pressure, immediately stop the INTEGRILIN infusion and any unfractionated heparin that is given concomitantly.

Arterial procedures

During treatment with eptifibatide there is a significant increase in bleeding rates, especially in the femoral artery area, where the catheter sheath is introduced. Take care to ensure that only the anterior wall of the femoral artery is punctured. Arterial sheaths may be removed when coagulation has returned to normal (e.g., when activated clotting time [ACT] is less than 180 seconds (usually 2-6 hours after discontinuation of heparin). After removal of the introducer sheath, careful haemostasis must be ensured under close observation.

Thrombocytopaenia

INTEGRILIN inhibits platelet aggregation, but does not appear to affect the viability of platelets. As demonstrated in clinical trials, the incidence of thrombocytopaenia was low, and similar in patients treated with eptifibatide or placebo. Thrombocytopaenia, including acute profound thrombocytopaenia, has been observed with eptifibatide administration (see section 4.8). Platelet counts should be monitored prior to treatment, within 6 hours of administration, and at least once daily thereafter while on therapy and immediately at clinical signs of unexpected bleeding tendency. If the patient experiences a confirmed platelet decrease to < 100,000/mm³, discontinue INTEGRILIN and unfractionated heparin and monitor and treat the patient appropriately. The decision to use platelet transfusions should be based upon clinical judgment on an individual basis. In patients with previous thrombocytopaenia from other parenteral GP IIb/IIIa inhibitors, there are no data with the use of INTEGRILIN, and thus these patients require close monitoring as noted above.

Heparin administration

Heparin administration is recommended unless a contraindication (such as a history of thrombocytopaenia associated with use of heparin) is present.

UA/NQMI