Tirofiban

Tirofiban is a non peptide intravenous glycoprotein IIb/IIIa receptor antagonist. It is used in high risk non ST elevation acute coronary syndrome and during percutaneous coronary intervention, together with aspirin and heparin. It has a short half life, so platelet function returns within hours of stopping. It needs dose reduction in kidney impairment. It is rarely available in East Africa.

Classification. Glycoprotein IIb/IIIa inhibitor; tyrosine derived non peptide.

Mechanism. Binds reversibly to the glycoprotein IIb/IIIa receptor on platelets, blocking fibrinogen binding and platelet aggregation, the final common step of platelet clumping.

Pharmacodynamics. Over 90% platelet inhibition within 30 minutes of a high dose bolus regimen. Bleeding time prolongs while the infusion runs. Platelet function returns to near normal 4 to 8 hours after stopping.

Pharmacokinetics. Half life about 2 hours. Little metabolism; about 65% excreted unchanged in urine and 25% in faeces. Clearance falls by 50% when creatinine clearance is under 30 mL/min. Protein binding about 65%.

Non ST elevation acute coronary syndrome, adult.

• Initial infusion 0.4 micrograms/kg/minute for 30 minutes.

• Then 0.1 micrograms/kg/minute for 48 to 108 hours (continue through angiography and for 12 to 24 hours after intervention; total not above 108 hours).

Percutaneous coronary intervention, adult. High dose bolus 25 micrograms/kg IV over 3 minutes or less, then 0.15 micrograms/kg/minute for 12 to 24 hours (maximum 48 hours).

Kidney impairment. Creatinine clearance 30 mL/min or less: halve the bolus and infusion rates (for acute coronary syndrome 0.2 micrograms/kg/minute for 30 minutes, then 0.05 micrograms/kg/minute; for intervention 0.075 micrograms/kg/minute).

Children. Not established.

Contraindications. Active bleeding or bleeding within 30 days; history of intracranial haemorrhage, tumour, aneurysm or arteriovenous malformation; stroke within 30 days; major surgery or trauma within 6 weeks; severe hypertension (above 180/110 mmHg); thrombocytopenia (under 100 x 10^9/L); acute pericarditis; aortic dissection; hypersensitivity; concurrent glycoprotein IIb/IIIa inhibitor.

Warnings. Bleeding (access site, gastrointestinal, genitourinary); thrombocytopenia (check at 6 hours and daily); weight and kidney function dose adjustments; stop before bypass surgery; use with caution in older adults.

Adverse effects. Bleeding, thrombocytopenia, bradycardia, dizziness, headache, nausea, fever, leg pain, rarely allergic reaction.

Interactions. Heparin, aspirin, clopidogrel, ticagrelor, prasugrel, thrombolytics, oral anticoagulants, non steroidal anti-inflammatory drugs: bleeding. Levothyroxine and omeprazole: modest changes in clearance.

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 doses when creatinine clearance is 30 mL/min or less.

• Liver impairment: no adjustment in mild disease; avoid with coagulopathy.

Formulations. Injection 0.25 mg/mL (250 mL bag, ready to use) and concentrate 5 mg/100 mL.

Administration. IV by infusion pump in a dedicated line. Do not give diazepam through the same line (incompatible). Protect from light until use.

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

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

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

Common prescribing errors. Using the full dose when creatinine clearance is under 30 mL/min; omitting platelet counts; giving with another glycoprotein IIb/IIIa inhibitor; confusing the acute coronary syndrome and intervention regimens; use in a patient with recent surgery or stroke.