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Tirofiban

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Title: Tirofiban  
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Tirofiban

Tirofiban
Systematic (IUPAC) name
(S)-2-(butylsulfonamino)-3-(4-[4-(piperidin-4-yl)butoxy]phenyl)propanoic acid
Clinical data
Trade names Aggrastat
AHFS/Drugs.com
MedlinePlus
Legal status
  • Prescription only
Routes Exclusively intravenous
Pharmacokinetic data
Bioavailability n/a (IV only)
Protein binding 65%
Half-life 2 hours
Identifiers
CAS number  YesY
ATC code B01
PubChem
DrugBank
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEBI  YesY
ChEMBL  YesY
Chemical data
Formula C22H36N2O5S 
Mol. mass 440.598 g/mol
 YesY   

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][2]


Contents

  • Medical use 1
  • Contraindications and precautions 2
    • Cautions 2.1
    • Adverse Reactions 2.2
    • Use in pregnancy 2.3
    • Pediatric use 2.4
    • Other precautions and laboratory exams 2.5
  • Side effects 3
  • Interactions 4
  • Pharmacology 5
  • Physical and chemical properties 6
  • History 7
  • References 8
  • External links 9

Medical use

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.

Cautions

  • Aggrastat can cause serious bleeding. If bleeding cannot be controlled discontinue Aggrastat.
  • Thrombocytopenia: Discontinue Aggrastat and heparin.

Adverse Reactions

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.

Pediatric use

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.

Side effects

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.

Post-marketing events have been the occurrence of intracranial bleeding, retroperitoneal bleeding, pulmonary hemorrhage and spinal-epidural hematoma. Fatal bleedings have been reported rarely.

Sometimes, thrombocytopenia was associated with chills, low-grade fever or bleeding complications (see above).

Cases of hypersenitivity including acute anaphylaxis have been seen.

Interactions

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.

Pharmacology

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.

Physical and chemical properties

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.

It is a modified version of an anticoagulant found in the venom of the saw-scaled viper Echis carinatus.[3]

History

The drug is marketed under the brand name AGGRASTAT in the US by Medicure Pharma and the rest of the world by Correvio International Sàrl.

References

  1. ^ 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".  
  2. ^ Van Drie, John H. (2007). "Computer-aided drug design: the next 20 years". J. Comput Aided Mol Des (Springer) 21 (10–11): 591–601.  
  3. ^ "Saw-Scaled Vipers".  

External links

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