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| {{drugbox
| | #REDIRECT [[Tirofiban#Pharmacology]] |
| | IUPAC_name = (2''S'')-2-(butylsulfonylamino)-3-[4-[4-(4-piperidyl)butoxy]phenyl<br>propanoic acid
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| | image = Tirofiban.svg
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| | width = 290px
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| | CAS_number = 144494-65-5
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| | ATC_prefix = B01
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| | ATC_suffix = AC17
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| | ATC_supplemental =
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| | PubChem = 60947
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| | DrugBank = APRD00304
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| | C = 22 | H = 36 | N = 2 | O = 5 | S = 1
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| | molecular_weight = 440.598 g/mol
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| | bioavailability = n/a ([[Intravenous therapy|IV]] only)
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| | protein_bound = 65%
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| | metabolism =
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| | elimination_half-life = 2 hours
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| | pregnancy_category =
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| | legal_status = Rx-only
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| | routes_of_administration = Exclusively [[Intravenous therapy|intravenous]]
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| }}
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| {{SI}}
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| {{CMG}}
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| '''Associate Editor-In-Chief:''' {{CZ}}
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| '''Tirofiban''' ([[International Nonproprietary Name|INN]], trade name '''Aggrastat®''') is an [[anticoagulant]] [[medication|drug]]. It belongs to a class of anticoagulants named [[glycoprotein IIb/IIIa inhibitors]].
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| ==Basic chemical and pharmacological information==
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| Tirofiban is a synthetic, nonpeptide inhibitor acting at glycoprotein-(GP)-receptors, type IIb/IIIa, in human [[thrombocyte]]s. It therefore constitutes an [[anticoagulant]], specifically an inhibitor of thrombocyte aggregation.
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| The drug is marketed in many countries under the brand name '''Aggrastat®''' by either [[Merck Sharp & Dohme]] or [http://www.medicurepharma.com Medicure Pharma].
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| It is sold in [[Route of administration|parenteral]] dosage forms intended and readily constituted for [[Intravenous therapy|IV]] administration containing 5 mg or 12.5 mg, respectively.
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| 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.
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| ==Indications==
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| 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 [[angioplasty|percutaneous transluminal coronary angioplasty]] (PTCA), to decrease the rate of refractory [[ischemia|ischemic]] conditions, new myocardial infarction and [[death]].
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| ==Contraindications and precautions==
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| Tirofiban is containdicated in patients with:
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| * known hypersensitivity to any component of the product
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| * active (internal) bleeding or a history of abnormal bleeding tendencies
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| * a history of [[intracranial hemorrhage]] or neoplasm, [[arteriovenous malformation]], or [[aneurysm]]
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| * patients who developed [[thrombocytopenia]] following prior exposure to tirofiban
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| * known [[coagulopathy]], platelet disorder or history of thrombocytopenia
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| * [[stroke]] within 30 days prior to hospitalization or any history of [[hemorrhagic stroke]]
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| * major [[surgery|surgical procedure]] or severe physical [[physical trauma|trauma]] within the previous month
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| * history, symptoms or findings suggestive of [[aortic dissection]]
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| * severe uncontrolled [[hypertension]]
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| * acute [[pericarditis]]
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| * [[cirrhosis]] or other clinically significant [[liver disease]]
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| * [[Angina pectoris|angina]] caused by obvious provoking factors ([[arrhythmia]], severe [[anemia]], [[hyperthyroidism]] or [[hypotension]])
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| ===Cautions===
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| Tirofiban should be used with caution in the following clinical situations:
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| * recent (<1 year) bleeding, including a history of [[gastrointestinal bleeding]], or genitouritary bleeding of clinical significance (e.g. [[hematuria|macrohematuria]])
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| * platelet count < 150,000/µl
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| * history of [[cerebrovascular disease]] in the past year
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| * hemorrhagic retinopathy
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| * chronic [[hemodialysis]]
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| ===Use in pregnancy===
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| 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.
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| Nursing mothers: It is not known whether tirofiban is excreted in [[breast milk|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.
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| ===Pediatric use===
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| Safety and effectiveness in children have not been established.
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| ===Other precautions and laboratory exams===
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| The [[partial thromboplastin time|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.
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| ==Side effects==
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| The following [[adverse drug reaction|side effect]]s were noted under treatment with tirofiban and heparin (and aspirin, if tolerated). Other drugs were used as necessary.
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| 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 %. [[Blood transfusion|Transfusion]]s 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.
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| 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.
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| Positive fecal and urine hemoglobin tests have also been reported.
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| [[Postmarketing surveillance|Post-marketing event]]s have been the occurrence of intracranial bleeding, retroperitoneal bleeding, [[pulmonary hemorrhage]] and spinal-epidural hematoma. Fatal bleedings have been reported rarely.
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| Sometimes, thrombocytopenia was associated with [[chills]], low-grade [[fever]] or bleeding complications (see above).
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| Cases of hypersenitivity including acute [[anaphylaxis]] have been seen.
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| ==Interactions==
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| 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.
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| ==Dosage regime==
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| Tirofiban is initially given as rapid [[intravenous infusion]] at a rate of 0.4 µg/kg and minute for 30 minutes. Upon completion of the initial infusion, the rate is decreased to 0.1 µg/kg and minute delivered as continuous infusion.
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| ==Duration of therapy==
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| Patients who do not show any signs of recurrent [[ischemia|ischemic]] symptoms and do not undergo [[angiography]] and [[angioplasty]] should be treated for at least 48 hours.
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| 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.
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| ==Summary of trial results==
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| In the [[multicenter trial|multicenter]], [[randomized controlled trial|randomized]], parallel, [[double-blind]] PRISM-PLUS [[clinical trial|trial]] component endpoints and a composite endpoint were defined for periods of 7 days, 30 days, and 6 months, respectively.
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| For the 7 days period the following results were obtained:
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| * '''Myocardial infarction and death''': Risk reduction for tirofiban/heparin compared with heparin alone: 42.8 %.
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| * '''Myocardial infarction''': Risk reduction for tirofiban/heparin compared with heparin alone: 46.6 %.
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| * '''Death''' : No significant difference.
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| * '''Refractory ischemia''': Risk reduction for tirofiban/heparin compared with heparin alone: 29.6 %.
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| * '''Composite endpoint''': Risk reduction for tirofiban/heparin compared with heparin alone: 31.6 %.
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| All results for the 7 days period were [[statistical significance|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.
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| ==References==
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| <div style="font-size: 95%">
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| <references/>
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| </div>
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| * AHFS Database Online
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| * Arzneimittel Datenbank (in German)
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| ==External links==
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| *[http://cvmed.stanford.edu/interventional/tirofiba.htm Tirofiban] - Stanford University.
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| *[http://www.fda.gov/cder/consumerinfo/druginfo/Aggra.HTM Aggrastat] - [[Food and Drug Administration]] (FDA) information.
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| *[http://www.merckfrosst.ca/e/products/monographs/AGGRASTAT_980-a_8_05-E.pdf Product monograph for Aggrastat] - Merck Frosst Canada.
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| {{Antithrombotics}}
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| [[Category:gpIIb/IIIa inhibitors]]
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| [[Category:Drugs]]
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| [[de:Tirofiban]]
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