|Systematic (IUPAC) name|
|Bioavailability||n/a (IV only)|
|Mol. mass||440.598 g/mol|
|(what is this?)|
Tirofiban (INN, trade name Aggrastat) is an antiplatelet drug. It belongs to a class of antiplatelet named glycoprotein IIb/IIIa inhibitors. Tirofiban is the first drug candidate whose origins can be traced to a pharmacophore-based virtual screening lead.
- 1 Basic chemical and pharmacological information
- 2 Indications
- 3 Contraindications and precautions
- 4 Side effects
- 5 Interactions
- 6 Dosage regimen
- 7 Duration of therapy
- 8 Summary of trial results
- 9 Synthesis
- 10 See also
- 11 References
- 12 External links
Basic chemical and pharmacological information
Tirofiban is a synthetic, non-peptide inhibitor acting at glycoprotein (GP) IIb/IIIa receptors in human platelets. It therefore constitutes an anticoagulant, specifically an inhibitor of platelet aggregation.
Tirofiban has a rapid onset and short duration of action after proper IV administration. Coagulation parameters turn to normal 4 to 8 hours after the drug is withdrawn.
Aggrastat is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).
Contraindications and precautions
Tirofiban is contraindicated in patients with:
- Known hypersensitivity to any component of Aggrastat.
- History of thrombocytopenia with prior exposure to Aggrastat.
- Active internal bleeding, or history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month.
- Aggrastat can cause serious bleeding. If bleeding cannot be controlled discontinue Aggrastat.
- Thrombocytopenia: Discontinue Aggrastat and heparin.
Bleeding is the most commonly reported adverse reaction.
Use in pregnancy
Tirofiban has been demonstrated to cross the placenta in pregnant rats and rabbits. Although the doses employed in these studies were a multiple of those used in human beings no adverse effects on the offspring in both animals have been seen. However, there are no adequate and well controlled studies in pregnant women. Therefore, tirofiban should be used during pregnancy only if clearly indicated.
Nursing mothers: It is not known whether tirofiban is excreted in human milk. However, significant levels of tirofiban are excreted in rat milk. Therefore, nursing should be discontinued during the period of drug administration and the milk discarded. Nursing may resume 24 hours after cessation of treatment with tirofiban.
Safety and effectiveness in children have not been established.
Other precautions and laboratory exams
The activated partial thromboplastin time (aPTT) is .the most reliable coagulation parameter and should be obtained regularly during treatment, particular if a bleeding episode occurs that may be associated with tirofiban therapy. Other important hematological parameters are platelet count, clotting time, hematocrit and hemoglobin. Proper technique regarding artery site access for sheath placement and removal of sheath should be followed. Arterial sheaths should be removed when the patient's activated clotting time is < 180 sec. or 2 to 6 hours following. withdrawal of heparin.
The following side effects were noted under treatment with tirofiban and heparin (and aspirin, if tolerated). Other drugs were used as necessary.
The major adverse effect is bleeding on local sites of clinical intervention and systemically (regarding parts of the body or the whole body system). Major bleeding has occurred in 1.4% of patients and minor bleeding in 10.5%. Transfusions were required to terminate bleeding and to improve bleeding-related anemia in 4.0% of all patients. Geriatric patients have experienced more bleeding episodes than younger, women more than men.
Thrombocytopenia was more often seen in the tirofiban + heparin group (1.5%) than in the heparin control group (0.8%). This adverse effect was usually readily reversible within days.
Positive fecal and urine hemoglobin tests have also been reported.
Cases of hypersenitivity including acute anaphylaxis have been seen.
The concomitant application of warfarin or other oral anticoagulants may increase the risk of serious bleeding events. The decision whether maintenance therapy with these drugs should be discontinued during tirofiban treatment has to be made by the responsible clinician.
New Dosing Regimen Approved by FDA in October, 2013.
High-Dose Bolus Regimen: Administer intravenously 25 mcg/kg over 3 minutes and then 0.15 mcg/kg/min for up to 18 hours. In patients with creatinine clearance ≤60 mL/min, give 25 mcg/kg over 3 minutes and then 0.075 mcg/kg/min.
Duration of therapy
Patients should be treated for up to 18 hours.
Summary of trial results
For the 7 days period the following results were obtained:
- Myocardial infarction and death: Risk reduction for tirofiban/heparin compared with heparin alone: 42.8%.
- Myocardial infarction: Risk reduction for tirofiban/heparin compared with heparin alone: 46.6%.
- Death : No significant difference.
- Refractory ischemia: Risk reduction for tirofiban/heparin compared with heparin alone: 29.6%.
- Composite endpoint: Risk reduction for tirofiban/heparin compared with heparin alone: 31.6%.
All results for the 7 days period were statistically highly significant. At 30 days and 6 months the benefits of tirofiban/heparin remained statistically significant, although the differences to the control group were shrinking.
- Hartzman, G.D.; Egbertson, M.S.; Halczenko, W.; Laswell, W.L.; Duggan, M.E.; Smith, R.L.; Naylor, A.M.; Manno, P.D.; Lynch, R.J.; Zhang, G.; Chang, C. T.-C.; Gould, R.J. (1992). "Non-Peptide Fibrinogen Receptor Antagonists. 1. Discovery and Design of Exosite Inhibitors". Journal of Medicinal Chemistry (American Chemical Society) 35 (24): 4640–4642. doi:10.1021/jm00102a020. PMID 1469694.
- Van Drie, John H. (2007). "Computer-aided drug design: the next 20 years". J. Comput Aided Mol Des (Springer) 21 (10–11): 591–601. doi:10.1007/s10822-007-9142-y. PMID 17989929. Retrieved 2008-06-23.
- "Saw-Scaled Vipers". University of Edinburgh. Retrieved 2008-06-23.
- Chung, J. Y. L.; Zhao, D.; Hughes, D. L.; Grabowski, E. J. J. (1993). "A practical synthesis of fibrinogen receptor antagonist MK-383. Selective functionalization of (S)-tyrosine". Tetrahedron 49 (26): 5767. doi:10.1016/S0040-4020(01)87943-6.
- Tirofiban - Stanford University.
- Aggrastat - Food and Drug Administration (FDA) information.
-  - Aggrastat Product Website- Medicure Pharma.