Tirofiban
Systematic (IUPAC) name
(2S)-2-(butylsulfonylamino)-3-[4-[4-(4-piperidyl)butoxy]phenyl propanoic acid
Identifiers
CAS number	144494-65-5
ATC code	B01AC17
PubChem	60947
DrugBank	APRD00304
Chemical data
Formula	C22H36N2O5S
Mol. weight	440.598 g/mol
Pharmacokinetic data
Bioavailability	n/a (IV only)
Protein binding	65%
Metabolism	?
Half life	2 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	? Image File history File links Tirofiban. ... IUPAC nomenclature is a systematic way of naming organic chemical compounds. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules . ... DrugBank is a database available at the University of Alberta that provides information about thousands of products. ... A chemical formula (also called molecular formula) is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... General Name, Symbol, Number carbon, C, 6 Chemical series nonmetals Group, Period, Block 14, 2, p Appearance black (graphite) colorless (diamond) Atomic mass 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless Atomic mass 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Atomic mass 15. ... General Name, Symbol, Number sulfur, S, 16 Chemical series nonmetals Group, Period, Block 16, 3, p Appearance lemon yellow Atomic mass 32. ... The molecular mass of a substance (less accurately called molecular weight and abbreviated as MW) is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of medication that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Many drugs are bound to Blood plasma proteins. ... Metabolism (from Greek μεταβολισμός metabolismos) is the biochemical modification of chemical compounds in living organisms and cells. ... The elimination half-life of a drug (or any xenobiotic agent) refers to the timecourse necessary for the quantity of the xenobiotic agent in the body (or plasma concentration) to be reduced to half of its original level through various elimination processes. ... Excretion is the biological process by which an organism chemically separates waste products from its body. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ...
Legal status	℞ Prescription only The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Routes	Exclusively intravenous

Tirofiban (INN, trade name Aggrastat®) is an anticoagulant drug. It belongs to a class of anticoagulants named glycoprotein IIb/IIIa inhibitors. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... In medicine, a glycoprotein IIb/IIIa inhibitors, also GpIIb/IIIa inhibitors, is class of antiplatelet agents. ...

Basic Chemical and Pharmacological Information

Tirofiban is a synthetic, nonpeptide inhibitor acting at glycoprotein-(GP)-receptors, type IIb/IIIa, in human thrombocytes. It therefore constitutes an anticoagulant, specifically an inhibitor of thrombocyte aggregation. A 250 ml bag of newly collected platelets. ... An anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. ...

The drug is marketed in many countries under the brand name Aggrastat® by either Merck Sharp & Dohme or Medicure Pharma. Merck may refer to: Merck & Co. ...

It is sold in parenteral dosage forms intended and readily constituted for IV administration containing 5mg or 12.5mg, respectively. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ...

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.

Indications

Tirofiban in combination with heparin and aspirin is indicated in the management of patients with unstable angina or non-Q-wave myocardial infarction, including patients who may subsequently undergo percutaneous transluminal coronary angioplasty (PCTA), to decrease the rate of refractory ischemic conditions, new myocardial infarction and death. Heparin is a highly sulfated glycosaminoglycan widely used as an injectable anticoagulant. ... Aspirin or acetylsalicylic acid (acetosal) is a drug in the family of salicylates, often used as an analgesic (against minor pains and aches), antipyretic (against fever), and anti-inflammatory. ... This page meets Wikipedias criteria for speedy deletion. ... A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream. ... Angioplasty is the mechanical, hydraulic dilation of a narrowed or totally obstructed arterial lumen, generally caused by atheroma (the lesion of atherosclerosis). ... In medicine, ischemia (Greek ισχαιμία, isch- is restriction, hema or haema is blood) is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. ... For other uses, see Death (disambiguation). ...

Contraindications and Precautions

Tirofiban is containdicated in patients with:

• known hypersensitivity to any component of the product
• active (internal) bleeding or a history of abnormal bleeding tendencies
• a history of intracranial hemorrhage or neoplasm, arteriovenous malformation, or aneurysm
• patients who developed thrombocytopenia following prior exposure to tirofiban
• known coagulopathy, platelet disorder or history of thrombocytopenia
• stroke within 30 days prior to hospitalization or any history of hemorrhagic stroke
• major surgical procedure or severe physical trauma within the previous month
• history, symptoms or findings suggestive of aortic dissection
• severe uncontrolled hypertension
• acute pericarditis
• cirrhosis or other clinically significant liver disease
• angina caused by obvious provoking factors (arrhythmia, severe anemia, hyperthyroidism or hypotension)

This article needs cleanup. ... Arteriovenous malformation or AVM is a congenital disorder of the veins and arteries that make up the vascular system . ... // Description An aneurysm (or aneurism) is a localized dilation or ballooning of a blood vessel by more than 50% of the diameter of the vessel and can lead to instant death. ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... This page is a candidate to be moved to Wiktionary. ... For other uses, see Stroke (disambiguation). ... Hemorrhagic stroke, or cerebral hemorrhage is a form of stroke that occurs when a blood vessel in the brain ruptures. ... Intraoperative X-Ray of a Humerus fixated by Kirschner wires Surgery (from the Greek meaning hand work) is the medical specialty that treats diseases or injuries by operative manual and instrumental treatment. ... In medicine, a trauma patient has suffered serious and life-threatening physical injury resulting in secondary complications such as shock, respiratory failure and death. ... Aortic dissection is a tear in the wall of the aorta (the largest artery of the body). ... For other forms of hypertension see hypertension (disambiguation). ... Pericarditis is inflammation of the pericardium. ... Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrotic scar tissue as well as regenerative nodules, leading to progressive loss of liver function. ... The liver is an organ in vertebrates including humans. ... angina tonsillaris see tonsillitis. ... A cardiac arrhythmia, also called cardiac dysrhythmia, is a disturbance in the regular rhythm of the heartbeat. ... This article discusses the medical condition. ... Hyperthyroidism (or overactive thyroid gland) is the clinical syndrome caused by an excess of circulating free thyroxine (T4) or free triiodothyronine (T3), or both. ... In physiology and medicine, hypotension refers to an abnormally low blood pressure. ...

Cautions

Tirofiban should be used with caution in the following clinical situations:

• recent (<1 year) bleeding, including a history of gastrointestinal bleeding, or genitouritary bleeding of clinical significance (e.g. macrohematuria)
• platelet count < 150,000
• history of cerebrovascular disease in the past year
• hemorrhagic retinopathy
• chronic hemodialysis

Gastrointestinal bleeding describes every form of hemorrhage (blood loss) in the gastrointestinal tract, from the pharynx to the rectum. ... In medicine, hematuria (or haematuria) is the presence of blood in the urine. ... Cerebrovascular disease is damage to the blood vessels in the brain, resulting in a stroke. ... A hemodialysis machine In medicine, hemodialysis, also haemodialysis, is a method for removing waste products such as potassium and urea, as well as free water from the blood when the kidneys are incapable of this (i. ...

Use in pregnancy

Tirofiban has been demonstrated to cross the placenta in pregnant rats and rabbits. Although the doses employeed 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. The placenta is an ephemeral (temporary) organ present only in female placental mammals during gestation (pregnancy). ... Species 50 species; see text *Several subfamilies of Muroids include animals called rats. ... This article or section does not cite its references or sources. ...

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. Breast milk usually refers to the milk produced by a human female which is usually fed to infants by breastfeeding. ...

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 assiociated to 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 partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) is a performance indicator measuring the efficacy of both the intrinsic and the common coagulation pathways. ... A 250 ml bag of newly collected platelets. ... The hematocrit (Ht or HCT) and packed cell volume (PCV) are measures of the proportion of blood volume that is occupied by red blood cells. ... 3-dimensional structure of hemoglobin. ...

Side effects

The following side effects were noted under treatment with tirofiban and heparin (and aspirin, if tolerated). Other drugs were used as necessary. An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ...

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 man. Blood transfusion is the taking of blood or blood-based products from one individual and inserting them into the circulatory system of another. ... This article discusses the medical condition. ...

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. Postmarketing surveillance is the practice of monitoring a pharmeceutical drug or device after it has been released on the market. ... This page meets Wikipedias criteria for speedy deletion. ...

Sometimes, thrombocytopenia was associated with chills, low-grade fever or bleeding complications (see above). This article does not cite its references or sources. ... An analogue medical thermometer showing the temperature of 38. ...

Cases of hypersenitivity including acute anaphylaxis have been seen. In medicine, anaphylaxis is a severe and rapid systemic allergic reaction. ...

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.

Dosage regime

Tirofiban is initially given as rapid intravenous infusion at a rate of 0.4µg/kg and minute for 30 minutes. Upon completion of the initial infusion, the rate is decreased to 0.1µg/kg and minute delivered as continuous infusion. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ...

Duration of therapy

Patients who do not show any signs of recurrent ischemic symptoms and do not undergo angiography and angioplasty should be treated for at least 48 hours. In medicine, ischemia (Greek ισχαιμία, isch- is restriction, hema or haema is blood) is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. ... Angiography or arteriography is a medical imaging technique in which an X-ray picture is taken to visualize the inner opening of blood filled structures, including arteries, veins and the heart chambers. ... Angioplasty is the mechanical, hydraulic dilation of a narrowed or totally obstructed arterial lumen, generally caused by atheroma (the lesion of atherosclerosis). ...

Patients proceeding into angiography and angioplasty should continue throughout both procedures and for at least 12 hours, and not more than 24 hours after angioplasty. Once a patient is clinically stable and no further coronary intervention is planned by the treating physician, the infusion should be discontinued.

Summary of trial results

In the multicenter, randomized, parallel, double-blind PRISM-PLUS trial component endpoints and a composite endpoint were defined for periods of 7 days, 30 days , and 6 months, respectively. Multicenter research trial. ... A randomized controlled trial (RCT) is a form of clinical trial, or scientific procedure used in the testing of the efficacy of medicines or medical procedures. ... Double-blind describes an especially stringent way of conducting an experiment, usually on living, conscious, human subjects. ... In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ...

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. In statistics, a result is significant if it is unlikely to have occurred by chance, given that a presumed null hypothesis is true. ... From Latin ex- + -periri (akin to periculum attempt). ...

References

• AHFS Database Online
• Arzneimittel Datenbank (in German)

External links

• Tirofiban - Stanford University.
• Aggrastat - Food and Drug Administration (FDA) information.
• Product monograph for Aggrastat - Merck Frosst Canada.

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