Tirofiban, sold under the brand name Aggrastat, is an antiplatelet

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

. It belongs to a class of antiplatelets named glycoprotein IIb/IIIa inhibitors. Tirofiban is a small molecule inhibitor of the protein-protein interaction between fibrinogen and the platelet integrin receptor GP IIb/IIIa and is the first drug candidate whose origins can be traced to a pharmacophore-based

virtual screening Virtual screening (VS) is a computational technique used in drug discovery to search libraries of small molecules in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor (biochemistry), r ...

lead Lead () is a chemical element; it has Chemical symbol, symbol Pb (from Latin ) and atomic number 82. It is a Heavy metal (elements), heavy metal that is density, denser than most common materials. Lead is Mohs scale, soft and Ductility, malleabl ...

. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Medical uses

Tirofiban is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in people with non-ST elevation acute coronary syndrome.

Contraindications and precautions

Tirofiban is contraindicated in patients with: * Known hypersensitivity to any component of tirofiban. * History of thrombocytopenia with prior exposure to tirofiban. * Active internal bleeding, or history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month.

Adverse reactions

Bleeding is the most commonly reported adverse reaction.

Use in pregnancy

Tirofiban has been demonstrated to cross the

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

in pregnant

rat Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include '' Neotoma'' (pack rats), '' Bandicota'' (bandicoo ...

s and

rabbit Rabbits are small mammals in the family Leporidae (which also includes the hares), which is in the order Lagomorpha (which also includes pikas). They are familiar throughout the world as a small herbivore, a prey animal, a domesticated ...

s. 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 Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by the mammary glands in the breasts of women. Breast milk is the primary source of nutrition for newborn infants, comprising fats, proteins, carbohydrates, and a va ...

. 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 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 Clotting time is a general term for the time required for a sample of blood to form a clot, or, in medical terms, coagulate. The term "clotting time" is often used when referring to tests such as the prothrombin time (PT), activated partial thro ...

hematocrit The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is nor ...

and

hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. 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 seconds or 2 to 6 hours following withdrawal of heparin.

Side effects

The following

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s 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 Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

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 bleeding have been reported rarely. Sometimes, thrombocytopenia was associated with

chills Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory ...

, low-grade

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

or bleeding complications (see above). Cases of hypersensitivity including

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

have occurred.

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.

Chemistry

Tirofiban is a synthetic, non-peptide inhibitor of the interaction of fibrinogen with the integrin glycoprotein IIb/IIIa on human

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

s. The Merck chemistry team of George Hartman, Melissa Egbertson and Wasyl Halczenko developed tirofiban from a lead compound discovered in focused screening of small molecule replacements of the key arginine-glycine-aspartic acid (Arg-Gly-Asp) subunit of fibrinogen. Computation of the distance between the charged Arg and Asp sites in fibrinogen provided guidance leading to directed screening success. Tirofiban constitutes an

antithrombotic An antithrombotic agent is a drug that reduces the formation of blood clots ( thrombi).http://cancerweb.ncl.ac.uk/cgi-bin/omd?antithrombotic Antithrombotics can be used therapeutically for prevention ( primary prevention, secondary prevention) or ...

, specifically an inhibitor of platelet aggregation. Tirofiban is a modified version of a molecule found in the venom of the saw-scaled viper '' Echis carinatus''.

History

The drug is marketed under the brand name Aggrastat in the US by Medicure Pharma, in China by Eddingpharm, and in the rest of the world by Correvio International Sàrl. According to the US Orange Book, it was first approved in the US on 20 April 2000. Patent numbers 5733919; 5965581 and 5972967 all expired in October 2016. Patent 5978698 expired in October 2017. Patent 6136794 expired in January 2019. Patent 6770660 expires in June 2023.