Bivalirudin

Bivalirudin is an intravenous direct thrombin inhibitor used as the anticoagulant during percutaneous coronary intervention, particularly when bleeding risk is high or heparin induced thrombocytopenia is present or suspected. It has a very short half life and is partly cleared by enzymes in the blood, so its effect fades within an hour of stopping. It is rarely available in East Africa.

Classification. Parenteral direct thrombin inhibitor; synthetic peptide.

Mechanism. Binds reversibly to the active site and the exosite of both free and clot bound thrombin, blocking fibrin formation and platelet activation.

Pharmacodynamics. Onset immediate with IV bolus. Prolongs activated clotting time, aPTT and thrombin time. Platelet counts are not affected.

Pharmacokinetics. Half life 25 minutes in normal kidney function (up to 3.5 hours in dialysis). About 80% cleared by proteolysis in plasma and 20% by the kidneys.

Percutaneous coronary intervention, adult.

• Bolus 0.75 mg/kg IV, then infusion 1.75 mg/kg/hour for the length of the procedure.

• Check activated clotting time 5 minutes after the bolus; give an additional bolus of 0.3 mg/kg if the value is under 225 seconds.

• Continue the infusion for up to 4 hours after the procedure if needed. After primary intervention for ST elevation myocardial infarction, a reduced infusion of 0.25 mg/kg/hour for 4 to 12 hours is sometimes added.

Heparin induced thrombocytopenia, adult. The same intervention regimen when a procedure is planned.

Kidney impairment. Creatinine clearance under 30 mL/min: infusion 1 mg/kg/hour. Dialysis: infusion 0.25 mg/kg/hour. The bolus is unchanged.

Children. Not established.

Contraindications. Active major bleeding; hypersensitivity (including to hirudins).

Warnings. Bleeding; acute stent thrombosis in the first hours after primary intervention in ST elevation myocardial infarction (consider the post procedure infusion); no antidote; antibody formation after repeated exposure; allergic reactions on re-exposure.

Adverse effects. Bleeding, access site haematoma, anaemia, hypotension, back pain, nausea, headache, thrombocytopenia (rare).

Interactions. Heparin, warfarin, antiplatelet drugs, thrombolytics, glycoprotein IIb/IIIa inhibitors: bleeding. Stop other parenteral anticoagulants before starting.

Special groups.

• Pregnancy: avoid unless essential; limited data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change.

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

• Kidney impairment: creatinine clearance under 30 mL/min, infusion 1 mg/kg/hour; dialysis, 0.25 mg/kg/hour.

• Liver impairment: no adjustment.

Formulations. Powder for injection, 250 mg in each vial.

Administration. Reconstitute each 250 mg vial with 5 mL of water for injection and dilute further to 5 mg/mL (or 0.5 mg/mL) in 0.9% sodium chloride or 5% glucose. Give the bolus over 1 minute and then run the infusion by pump.

Baseline. Haemoglobin, platelet count, creatinine clearance, weight, coagulation tests.

Monitoring. Activated clotting time 5 minutes after the bolus and during long procedures; access site; haemoglobin; creatinine.

Stopping. Stop at the end of the procedure or at the end of the planned infusion; effect is gone within 1 to 2 hours.

Common prescribing errors. Not adjusting for kidney function; not checking activated clotting time; giving together with heparin; confusing mg/kg/hour with mg/kg; failing to continue the infusion after primary intervention where indicated.