Tirofiban

440.6

440.60

1806241-263-5

GGX234SI5H

DTXSID20162730

C76405

White solid

B01AC17|B - Blood and blood forming organs

2942000000

113

1.4

Solid

1.154±0.06 g/cm3(Predicted)

223-225 °C

611.7±65.0 °C(Predicted)

323.7±34.3 °C

1.532

H2O: Very slightly soluble

5.2X10-16 mmHg at 25 deg C /Estimated/

Henry's Law constant = 7.4X10-15 atm-cu m/mole at 25 °C /Estimated/

pKa = 3.3 (carboxylic acid); pKa = 10.5 (amine) /Estimated/

White to off-white, non-hygroscopic, free-flowing powder; MW: 495.08; very slightly soluble in water. /Tirofiban hydrochloride salt mono hydrate/|Hydroxyl radical reaction rate constant = 1.6X10-10 cu cm/molec-sec at 25 °C /Estimated/

II

8

UN3261

3

36/37/38

26

YP2364100

Xi

P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501

H315

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl tirofiban hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Tirofiban Hydrochloride/

|Warning|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 38 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Concurrent use /with other platelet aggregation inhibitors (especially inhibitors of platelet receptor GP IIb/IIIa) is not recommended.|Data from a large clinical study indicate that concomitant administration of tirofiban and levothyroxine or omeprazole was associated with a higher clearance of tirofiban; the clinical importance of this effect is not known.

65%

Tirofiban's production and use as an antithrombotic(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 40,000(SRC), determined from a structure estimation method(2), indicates that tirofiban is expected to be immobile in soil(SRC). Volatilization of tirofiban from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.4X10-15 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Estimated pKa values of 3.3 (carboxylic acid group) and 10.5 (amino group)(4) indicate that tirofiban will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from moist soil is not expected to be an important fate process. Tirofiban is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-16 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation data were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 40,000(SRC), determined from a structure estimation method(2), indicates that tirofiban is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.4X10-15 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Estimated pKa values of 3.3 (carboxylic acid group) and 10.5 (amino group)(5) indicate that tirofiban will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from water surfaces is not expected to be an important fate process. According to a classification scheme(6), an estimated BCF of 3.2(SRC), from an estimated log Kow of 1.4(7) and a regression derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation data were not available(SRC, 2005).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), tirofiban, which has an estimated vapor pressure of 5.2X10-16 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase tirofiban may be removed from the air by wet and dry deposition(SRC). Tirofiban does not contain chromophores that absorb light at wavelengths >290 nm and therefore is not be expected to be susceptible to direct photolysis by sunlight(SRC).

Tirofiban is not expected to undergo hydrolysis in the environment due to the lack of hydrolyzable functional groups(1). Tirofiban does not contain chromophores that absorb light at wavelengths >290 nm and therefore is not be expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.2 was calculated for tirofiban(SRC), using an estimated log Kow of 1.4(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for tirofiban can be estimated to be 40,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that tirofiban is expected to be immobile in soil.

The Henry's Law constant for tirofiban is estimated as 7.4X10-15 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that tirofiban is expected to be essentially nonvolatile from water surfaces(2). Estimated pKa values of 3.3 (carboxylic acid group) and 10.5 (amino group)(3) indicate that tirofiban will exist as a zwitterion at pH values of 5 to 9 and therefore volatilization from moist soil surfaces and water surfaces is not expected to be an important fate process. Tirofiban is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 5.2X10-16 mm Hg(SRC), determined from a fragment constant method(4).

Occupational exposure to tirofiban may occur through inhalation and dermal contact with this compound at workplaces where tirofiban is produced or used. Exposure to the drug among the general population exposure may be limited to those individuals being administered tirofiban (an antithrombotic). (SRC)

For treatment, in combination with heparin, of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy.|FDA Label

Antithrombotic; in treatment of unstable angina.|Tirofiban is indicated, in combination with heparin, for the prevention of acute cardiac ischemic complications in patients with acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction). these patients are at high risk for myocardial infarction and sudden death due to progression of total coronary artery occlusion, whether managed medically or with percutaneous coronary intervention (PCI). Note: Acute coronary syndrome is defined as prolonged (>/= 10 minutes) or repetitive symptoms of cardiac ischemia occurring at rest or with minimal exertion, associated with either ST-T wave changes on electrocardiogram or elevated cardiac enzymes. This definition includes unstable angina and non-Q-wave myocardial infarction but excludes myocardial infarction that is associated with Q waves or nontransient ST-segment elevation. /Included in US product labeling/

Adverse cardiovascular effects that occurred in greater than 1% of patients receiving tirofiban plus heparin in clinical trials were bradycardia (4%) or dissection of the coronary artery (5%). Edema/swelling or vasovagal reactions were reported in 2% of patients receiving tirofiban and heparin in these trials.|Sweating was reported in 2% of patients receiving tirofiban and heparin in controlled clinical trials. Anaphylaxis and/or urticaria requiring discontinuance of therapy was not reported in clinical trials of tirofiban, but anaphylaxis and other severe allergic reactions have been reported during postmarketing experience. Such reactions have occurred on the first day of tirofiban infusion, during initial treatment, and during readministration of the drug. Some severe allergic reactions have been associated with severe thrombocytopenia (platelet counts less than 10,000/cu mm).|Pelvic pain occurred in 6%, leg pain in 3%, and dizziness in 3% of patients receiving tirofiban plus heparin in clinical trials. Other adverse effects reported in greater than 1% of patients receiving tirofiban plus heparin in clinical trials include headache, nausea, and fever.|The administration of tirofiban in patients with acute unstable angina or non-ST-segment elevation myocardial infarction has been associated with a small increase in the frequency of major bleeding compared with heparin and aspirin therapy alone.|For more Drug Warnings (Complete) data for TIROFIBAN (11 total), please visit the HSDB record page.

Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, and inhibits platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion. Tirofiban has been recently shown in patients with unstable angina to reduce ischemic events at 48 hours following infusion when compared to standard heparin therapy.

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)|Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN. (See all compounds classified as Fibrinolytic Agents.)

It is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban.|22 to 42 L|213 - 314 mL/min [Healthy subjects]|Not highly bound to plasma proteins; protein binding is concentration-independent over the range of 0.01 to 25 ug/mL. Unbound fraction in human plasma is 35%.|Tirofiban is approximately 65% bound to plasma proteins ... The steady-state volume of distribution of tirofiban ranges from 22-42 L. It is not known whether tirofiban is distributed into milk or crosses the placenta in humans; however, the drug is distributed into milk in rats and crosses the placenta in pregnant rats and rabbits.|About 65 and 25% of a single dose of tirofiban is excreted in urine and feces, respectively, principally as unchanged parent drug. Plasma clearance of tirofiban in healthy individuals ranges from 213-314 mL/minute, with renal clearance accounting for 39-69% of plasma clearance. In patients with coronary artery disease, the plasma clearance of tirofiban ranges from 152-267 mL/minute and does not appear to be influenced by gender or race; renal clearance in these patients accounts for 39% of plasma clearance. Plasma clearance is about 19-26% lower in geriatric patients (those exceeding 65 years of age) with coronary artery disease than in younger patients. Plasma clearance appears to be independent of dose in healthy individuals and is not appreciably affected by mild to moderate hepatic insufficiency. In patients with renal impairment (creatinine clearance less than 30 mL per minute), including those requiring hemodialysis, plasma clearance of tirofiban is decreased by greater than 50% compared with that in individuals with normal renal function. Tirofiban is removed by hemodialysis.

Metabolism appears to be limited.

2 hours|Elimination: Approximately 2 hours.

Tirofiban is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. Platelet aggregation inhibition is reversible following cessation of the infusion of tirofiban.|Tirofiban inhibits platelet aggregation by reversibly binding to the platelet receptor glycoprotein (GP) IIb/IIIa of human platelets, thus preventing the binding of fibrinogen. Inhibition of platelet aggregation occurs in a dose- and concentration-dependent manner.

Following assessment of the patient's clinical condition; treatment consists of cessation or adjustment of the tirofiban infusion as appropriate. Tirofiban can be removed by hemodialysis.|Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ Limited information is available on the acute toxicity of tirofiban. In general, overdosage of tirofiban in humans may be expected to produce effects that are extensions of the pharmacologic and adverse effects of the drug, predominantly bleeding. The most frequently reported manifestation of overdosage was bleeding, principally minor bleeding at mucocutaneous and cardiac catheterization sites. Inadvertent overdosage with tirofiban has occurred in doses of up to twice those recommended for an IV loading infusion and up to 9.8 times higher than the recommended maintenance infusion dosage of 0.15 ug/kg per minute

Aggrastat

Parenteral: For injection, concentrate, for IV infusion 250 ug (of tirofiban) per mL (6.25 and 12.5 mg) Aggrastat, (Merck). /Tirofiban hydrochloride/|Parenteral: Injection, for IV infusion 50 ug (of tirofiban) per mL (12.5 mg) in 0.9% sodium chloride Aggrastat Premixed in Iso-osmotic Sodium Chloride Injection (in IntraVia flexible container), (Merck). /Tirofiban hydrochloride in sodium chloride/

Specific nonpeptide platelet fibrinogen receptor (GPIIb/IIIa) antagonist.|Information available in 2005 indicated that Tirofiban was used in the manufacture of pharmaceutical preparations in the following countries: Spain (1)|Information available in 2005 indicated that Tirofiban hydrochloride monohydrate was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Costa Rica, Croatia, Czech Republic, Denmark, Ecuador, El Salvador, Finland, France, Germany, Greece, Guatemala, Honduras, Hong Kong, Hungary, Ireland, Israel, Italy, Malaysia, Mexico, Netherlands, New Zealand, Nicaragua, Norway, Panama, Poland, Romania, Singapore, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, United Kingdom, United States (1,2)

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients