Tirofiban Other names: Tirofiban hydrochloride

There is evidence from clinical studies that the risk of bleeding increases with decreasing creatinine clearance and hence also reduced plasma clearance of tirofiban. Patients with decreased renal function (creatinine clearance <60ml/min) should therefore be carefully monitored for bleeding during treatment with tirofiban and the heparin effect should be carefully monitored.

In severe kidney failure (creatinine clearance <30 ml/min) the dosage of tirofiban should be reduced by 50%.

The concomitant administration of tirofiban and unfractionated heparin increases the prolongation of the bleeding time to a greater extent as compared to unfractionated heparin alone.

With the concurrent use of tirofiban, unfractionated heparin, ASA, and clopidogrel there was a comparable incidence of bleeding than when only unfractionated heparin, ASA, and clopidogrel were used together.

Tirofiban is not recommended in thrombolytic therapy – concurrent or less than 48 hours before administration of tirofiban hydrochloride or concurrent use of drugs that increase the risk of bleeding to a relevant degree (e.g. oral anticoagulants, other parenteral GP IIb/IIIa inhibitors, dextran solutions).

There is insufficient experience with the use of tirofiban hydrochloride in these conditions; however, an increased risk of bleeding is suspected.

The concomitant administration of tirofiban and ASA increases the inhibition of platelet aggregation to a greater extent than ASA alone, as measured by ex vivo APD-induced platelet aggregation test.

There is limited experience with concomitant administration of tirofiban with enoxaparin. The concomitant administration of tirofiban with enoxaparin is associated with a higher frequency of cutaneous and oral bleeding events, but not in TIMI bleeds**, when compared with the concomitant administration of tirofiban and unfractionated heparin. An increased risk of serious bleeding events associated with the concomitant administration of tirofiban and enoxaparin cannot be excluded, particularly in patients given additional unfractionated heparin in conjunction with angiography and/or PCI. The efficacy of tirofiban in combination with enoxaparin has not been established. The safety and efficacy of tirofiban with other low molecular weight heparins has not been investigated.

^** TIMI major bleeds are defined as a haemoglobin drop of >50g/l with or without an identified site, intracranial haemorrhage, or cardiac tamponade. TIMI minor bleeds are defined as a haemoglobin drop of >30 g/l but ≤50 g/l with bleeding from a known site or spontaneous gross haematuria, haematemesis, or haemoptysis. TIMI “loss no site” is defined as a haemoglobin drop >40 g/l but <50 g/l without an identified bleeding site.

Special caution should be used during concurrent administration of ticlopidine, clopidogrel, adenosine, dipyridamole, sulfinpyrazone, and prostacyclin.

Concomitant use of warfarin with tirofiban plus heparin was associated with an increased risk of bleeding.

Tirofiban should be used with special caution in the following conditions and patient groups:

• Recent epidural procedure (including lumbar puncture and spinal anaesthesia).
• Severe acute or chronic heart failure.
• Cardiogenic shock.
• Mild to moderate liver insufficiency.
• Haemoglobin concentration less than 11 g/dl or haematocrit <34%.

There is insufficient experience with the use of tirofiban hydrochloride in the following diseases and conditions, however, an increased risk of bleeding is suspected. Therefore, tirofiban hydrochloride is not recommended in:

• Traumatic or protracted cardiopulmonary resuscitation, organ biopsy or lithotripsy within the past two weeks.
• Active peptic ulcer within the past three months.
• Acute pericarditis.
• Active or a known history of vasculitis.
• Suspected aortic dissection.
• Haemorrhagic retinopathy.
• Occult blood in the stool or haematuria.

There are no or limited amount of data from the use of tirofiban in pregnant women. Animal studies are insufficient with respect to the reproductive toxicity. Tirofiban is not recommended used during pregnancy unless clearly necessary.

It is not known whether tirofiban is excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of tirofiban in milk. A risk to the newborn cannot be excluded. A decision should be made whether to discontinue breastfeeding or discontinue tirofiban therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Fertility and reproductive performance were not affected in studies with male and female rats treated with different doses of tirofiban.

However, animal studies are insufficient to draw conclusions with respect to reproductive toxicity in humans.

No data are available on whether tirofiban impairs the ability to drive or use machines.