The pharmacokinetics and pharmacodynamics of Aggrastat were investigated when concomitantly administered with enoxaparin (1 milligram/kg subcutaneously every 12 hours) and compared with the combination of Aggrastat and unfractionated heparin. There was no difference in the clearance of Aggrastat between the two groups.

5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.

Fertility and reproductive performance were not affected in studies with male and female rats given intravenous doses of tirofiban hydrochloride up to 5 mg/kg/day. These dosages are approximately 22-fold higher than the maximum recommended daily dose in humans.

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

Tirofiban crosses the placenta in rats and rabbits.

6. Pharmaceutical particulars
6.1 List of excipients
Sodium chloride, sodium citrate dihydrate, citric acid anhydrous, water for injection, hydrochloric acid and/or sodium hydroxide (for pH adjustment).

6.2 Incompatibilities
Incompatibility has been found with diazepam. Therefore, Aggrastat and diazepam should not be administered in the same intravenous line.

No incompatibilities have been found with Aggrastat and the following intravenous formulations: atropine sulfate, dobutamine, dopamine, epinephrine HCl, furosemide, heparin, lidocaine, midazolam HCl, morphine sulfate, nitroglycerin, potassium chloride, propanolol HCl and famotidine injection.

6.3 Shelf life
Aggrastat Solution : 3 years.

Aggrastat Concentrate: 3 years.

From a microbiological point of view the diluted solution for infusion should be used immediately. If not used immediately, in use storage conditions are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage
Aggrastat Solution:

Do not freeze. Keep container in foil overpouch to protect from light.

Aggrastat Concentrate:

Do not freeze. Keep container in outer carton to protect from light.

For storage conditions after dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container
Aggrastat Solution:

250 ml IntraVia™ container (PL 2408 plastic), colourless, 3-layer polyolefine film with outlet port and PVC tube with blue top. It is packed in a preprinted foil overpouch.

Pack sizes: 1 or 3 containers with 250 ml solution for infusion. Not all pack sizes may be marketed.

Aggrastat Concentrate:

50 ml Type I glass vial.

6.6 Special precautions for disposal and other handling
Aggrastat Solution:

Some opacity of the plastic due to moisture absorption during the sterilisation process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired.

Aggrastat Concentrate:

Aggrastat concentrate for solution for infusion must be diluted before use.

See section 4.2.

Any unused medicinal product or waste material should be