AGGRASTAT

What it is

AGGRASTAT contains tirofiban hydrochloride. It is a sterile concentrated solution for intravenous infusion after dilution and is supplied in a 50 mL glass vial. Tirofiban is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and is a platelet aggregation inhibitor.

Approved indications

— Prevention of cardiac ischaemic events in patients with unstable angina or non-Q-wave myocardial infarction, when used in combination with heparin.

Dosing overview

AGGRASTAT should be administered intravenously at an initial infusion rate of 0.4 μg/kg/min for 30 minutes, then continued at a maintenance infusion rate of 0.1 μg/kg/min. It should be given with heparin (usually an intravenous bolus dose of 5000 U simultaneously with the start of therapy with AGGRASTAT, then approximately 1000 U per hour titrated on the basis of APTT, which should be about twice the normal value). In the study that demonstrated efficacy, AGGRASTAT in combination with heparin was generally continued for a minimum of 48 hours and up to 108 hours, and this infusion can be continued through angiography and should be continued up to 12 to 24 hours post-angioplasty/atherectomy. The dosage of AGGRASTAT should be decreased by 50% in patients with severe renal insufficiency (creatinine clearance <30 mL/min).

Key safety warnings

Because tirofiban inhibits platelet aggregation, caution should be employed when it is used with other drugs that affect haemostasis. During therapy with tirofiban, patients should be monitored for potential bleeding. When treatment of bleeding is required, discontinuation of the drug should be considered. Consideration may also be given to transfusions. Fatal bleedings have been reported. Tirofiban is associated with minor increases in bleeding rates particularly at the site of arterial access for femoral sheath placement. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured, avoiding a Seldinger (through and through) technique for obtaining sheath access. Care should be taken to obtain proper haemostasis after removal of the sheaths followed by close observation. Platelet counts, and haemoglobin and haematocrit should be monitored prior to treatment, within 6 hours following the bolus or loading infusion, and at least daily thereafter during therapy with tirofiban (or more frequently if there is evidence of significant decline). Patients treated with tirofiban, with heparin, were more likely to experience decreases in platelet counts than the control group. These decreases were reversible upon discontinuation of tirofiban.

Contraindications

Tirofiban is contraindicated in the following patient groups: known hypersensitivity to any component of the product; active internal bleeding or a history of bleeding diathesis within the previous 30 days. Tirofiban is also contraindicated in patients with a history of intracranial haemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; a history of thrombocytopenia following prior exposure to tirofiban; history of stroke within 30 days or any history of haemorrhagic stroke; major surgical procedure (including epidural or spinal anaesthesia) or severe physical trauma within 1 month; history, symptoms, or findings suggestive of aortic dissection; severe uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg); concomitant use of another parenteral GP IIb/IIIa inhibitor; and acute pericarditis.

PBS listing

AGGRASTAT 12.5 mg (as hydrochloride) in 50 mL solution concentrate for intravenous infusion is listed on the PBS with streamlined restriction at an ex-manufacturer price of A$155.09.

Regulatory history

AGGRASTAT tirofiban 12.5 mg/50 mL injection vial was first registered on the ARTG on 29 April 1999. Initial approval for the current formulation (TIROFIBAN JUNO) was granted on 9 May 2014.