Eptifibatide

Eptifibatide is a cyclic heptapeptide that reversibly blocks the platelet glycoprotein IIb/IIIa receptor. It is used in high risk non ST elevation acute coronary syndrome and during percutaneous coronary intervention. It has a short half life, so its effect wears off within hours of stopping. It needs dose reduction in kidney impairment. It is rarely available in East Africa.

Classification. Glycoprotein IIb/IIIa inhibitor; cyclic peptide.

Mechanism. Binds reversibly to the glycoprotein IIb/IIIa receptor at the arginine glycine aspartate recognition site, blocking fibrinogen binding and platelet aggregation.

Pharmacodynamics. Over 80% platelet inhibition within 15 minutes of the bolus. Platelet function returns to normal within 4 to 8 hours of stopping.

Pharmacokinetics. Half life about 2.5 hours; 25% protein bound. About 50% excreted unchanged in urine; the rest is metabolised. Clearance falls with creatinine clearance under 50 mL/min.

Non ST elevation acute coronary syndrome (medical management or before intervention), adult.

• Bolus 180 micrograms/kg IV (maximum 22.6 mg).

• Then infusion 2 micrograms/kg/minute (maximum 15 mg/hour) for up to 72 hours (or until discharge or the start of bypass surgery).

• If percutaneous coronary intervention is done, continue for 20 to 24 hours after the procedure (a total of up to 96 hours).

Percutaneous coronary intervention, adult. Bolus 180 micrograms/kg, then infusion 2 micrograms/kg/minute, and a second bolus 180 micrograms/kg 10 minutes after the first; continue the infusion for 18 to 24 hours after the procedure (at least 12 hours).

Kidney impairment. Creatinine clearance 30 to 50 mL/min: bolus 180 micrograms/kg; infusion 1 microgram/kg/minute. Creatinine clearance under 30 mL/min or dialysis: contraindicated.

Children. Not established.

Contraindications.

• Active bleeding or a history of bleeding diathesis within 30 days
• Stroke within 30 days or any haemorrhagic stroke
• Major surgery or trauma within 6 weeks
• Severe uncontrolled hypertension (above 200/110 mmHg)
• Thrombocytopenia (under 100 x 10^9/L)
• Creatinine clearance under 30 mL/min or dialysis
• Concurrent use of another glycoprotein IIb/IIIa inhibitor
• Hypersensitivity

Warnings. Bleeding (access site most common); thrombocytopenia (check platelets at 6 hours and daily); weight over 121 kg: apply the maximum doses; stop the infusion before bypass surgery; do not use with a full dose fibrinolytic.

Adverse effects. Bleeding, thrombocytopenia, hypotension, access site haematoma, anaemia, rarely allergic reactions.

Interactions. Heparin, aspirin, clopidogrel, ticagrelor, prasugrel, anticoagulants, thrombolytics, non steroidal anti-inflammatory drugs: increased bleeding risk. Other glycoprotein IIb/IIIa inhibitors: contraindicated.

Special groups.

• Pregnancy: avoid; no data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change.

• Older adults: higher bleeding risk; check kidney function.

• Kidney impairment: halve the infusion at creatinine clearance 30 to 50 mL/min; contraindicated below 30 mL/min.

• Liver impairment: no adjustment; avoid in significant coagulopathy.

Formulations. Injection 0.75 mg/mL (100 mL vial) and 2 mg/mL (10 mL vial).

Administration. IV bolus by push over 1 to 2 minutes, then infusion by pump in a dedicated line; may be given undiluted. Store refrigerated; may be kept at room temperature for 2 months.

Baseline. Haemoglobin, platelet count, coagulation tests (aPTT, INR), creatinine clearance, weight, blood pressure.

Monitoring. Platelet count and haemoglobin at 6 hours and then daily; activated clotting time or aPTT with heparin; creatinine; access site and bleeding signs.

Stopping. Stop the infusion at the end of the planned period (or earlier for bleeding). Platelet function recovers within 4 to 8 hours.

Common prescribing errors. Giving full dose in kidney impairment; omitting the second bolus in intervention; not checking platelet counts; using with another glycoprotein IIb/IIIa inhibitor; giving to a patient with recent stroke or surgery.