Abciximab

Abciximab is a monoclonal antibody fragment that blocks the platelet glycoprotein IIb/IIIa receptor, preventing platelet aggregation. It was used during percutaneous coronary intervention for high risk acute coronary syndrome but is now rarely produced or stocked, and it is not available in East Africa. Its effect lasts for days, and repeat use can cause immune reactions and low platelet counts.

Classification. Glycoprotein IIb/IIIa inhibitor; chimeric monoclonal antibody Fab fragment.

Mechanism. Binds the glycoprotein IIb/IIIa receptor on platelets, blocking fibrinogen binding, the final common step of platelet aggregation. It also binds the vitronectin receptor and Mac-1.

Pharmacodynamics. Over 80% receptor blockade within 10 minutes of the bolus. Platelet aggregation returns to 50% of normal in about 24 to 48 hours after stopping the infusion (platelet function recovers over 5 to 7 days).

Pharmacokinetics. Initial plasma half life under 10 minutes; second phase 30 minutes; the antibody stays bound to platelets for days. Cleared by binding to platelets and by proteolysis.

Percutaneous coronary intervention, adult.

• Bolus 0.25 mg/kg IV, given 10 to 60 minutes before the intervention.

• Then infusion 0.125 micrograms/kg/minute (maximum 10 micrograms/minute) for 12 hours.

• Give with aspirin and unfractionated heparin (reduced dose, targeting an activated clotting time of 200 to 250 seconds).

Unstable angina not responding to therapy, with planned intervention within 24 hours, adult. Bolus 0.25 mg/kg, then infusion 10 micrograms/minute for 18 to 24 hours, ending 1 hour after the intervention.

Children. Not established.

Contraindications. Active internal bleeding; stroke within 2 years or any haemorrhagic stroke; intracranial tumour, aneurysm or arteriovenous malformation; major surgery or trauma within 6 weeks; severe uncontrolled hypertension; thrombocytopenia (under 100 x 10^9/L); vasculitis; oral anticoagulation with INR above 1.2; haemodialysis dependence; hypersensitivity to murine proteins.

Warnings. Major bleeding; acute and delayed thrombocytopenia (check platelets at 2 to 4 hours and at 24 hours); repeat exposure can cause human anti chimeric antibodies and hypersensitivity; stop the infusion for serious bleeding; platelet transfusion reverses the effect.

Adverse effects. Bleeding, thrombocytopenia, hypotension, bradycardia, nausea, back pain, chest pain, allergic reaction.

Interactions. Anticoagulants (heparin, warfarin), aspirin, other antiplatelet drugs, thrombolytics, non steroidal anti-inflammatory drugs: bleeding. Dextran: increased bleeding risk.

Special groups.

• Pregnancy: avoid; no data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change.

• Older adults: higher bleeding risk; consider alternatives.

• Kidney impairment: no adjustment; avoid in dialysis.

• Liver impairment: use with caution (bleeding risk).

Formulations. Injection 2 mg/mL, 5 mL vial (10 mg).

Administration. IV through a 0.2 or 0.22 micrometre low protein binding filter; bolus then infusion by pump in a dedicated line. Do not mix with other drugs. Store refrigerated; do not shake.

Baseline. Haemoglobin, platelet count (at least 100 x 10^9/L), coagulation tests, creatinine, blood pressure.

Monitoring. Platelet count at baseline, 2 to 4 hours and 24 hours; haemoglobin; activated clotting time during the procedure; access site and bleeding signs.

Stopping. Stop the infusion at 12 hours (or earlier for bleeding). Remove sheaths when the activated clotting time is below 175 seconds and the infusion has been off for the required period.

Common prescribing errors. Giving full dose heparin with it; repeat administration without checking for antibodies; omitting platelet counts; using it in patients with recent surgery or stroke; infusing without a filter.