4.5 Interaction with other medicinal products and other forms of interaction
The use of several platelet aggregation inhibitors increases the risk of bleeding, likewise their combination with heparin, warfarin and thrombolytics. Clinical and biological parameters of haemostasis should be regularly monitored.

The concomitant administration of Aggrastat 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. The concomitant administration of Aggrastat 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 Aggrastat, unfractionated heparin, ASA, and clopidogrel there was a comparable incidence of bleeding than when only unfractionated heparin, ASA, and clopidogrel were used together (see sections 4.4 and 4.8).

Aggrastat prolonged bleeding time; however, the combined administration of Aggrastat and ticlopidine did not additionally affect bleeding time.

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

Aggrastat 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.

4.6 Fertility, pregnancy and lactation
Pregnancy

There are no or limited amount of data from the use of tirofiban hydrochloride in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). Aggrastat is not recommended during pregnancy unless clearly necessary.
Breastfeeding

It is unknown whether tirofiban hydrochloride is excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of tirofiban hydrochloride in milk (for details see section 5.3). A risk to the newborn cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue Aggrastat 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 hydrochloride (see section 5.3).

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

4.7 Effects on ability to drive and use machines
Not relevant.

4.8 Undesirable effects
a. Summary of safety profile

The most common adverse reaction reported during therapy with Aggrastat, when used concomitantly with heparin, aspirin and other oral anti-platelet agents, was bleeding, which usually involved mild mucocutaneous bleeding or mild catheterization-site bleeding.