These Highlights Do Not Include All The Information Needed To Use Tirofiban Hydrochloride Injection Safely And Effectively. See Full Prescribing Information For Tirofiban Hydrochloride Injection.

Administration Instructions

• Withdraw the bolus dose of Tirofiban Hydrochloride Injection from the 100 mL or 250 mL premixed bag into a syringe. Do not dilute. Administer the bolus dose within 5 minutes via a syringe or IV pump.
• Immediately following the bolus dose administration, administer the maintenance infusion from the 100 mL or 250 mL premixed bag via an IV pump.
• Discard any unused portion left in the bag.

The recommended bolus volume using the 100 mL or 250 mL premixed bag can be calculated using the following equation:

The recommended infusion rate for patients with CrCl (Creatinine Clearance) > 60 mL/min using the 100 mL or 250 mL premixed bag can be calculated using the following equation:

Example calculation of infusion rate for 60 kg patient with CrCl > 60 mL/min using the 100 mL or 250 mL premixed bag:

Principal Display Panel – 100 mL Carton Label

NDC 14789-101-02

PROTECT FROM LIGHT DURING STORAGE

RECOMMENDED FOR USE WITH CALIBRATED INFUSION DEVICE

PREMIXED INJECTION

Tirofiban Hydrochloride

Injection

5 mg per 100 mL (50 mcg per mL)

100 mL

Single-dose Container

Rx Only

Iso-osmotic

Sterile Nonpyrogenic

Each 100mL contains:Tirofiban hydrochloride equivalent to 5 mg tirofiban,

0.9 g sodium chloride, 54 mg sodium citrate dihydrate, 3.5 mg citric acid

monohydrate, Water for Injection. pH may have been adjusted with

hydrochloric acid and/or sodium hydroxide.

Usual Dosage:Intravenously as directed by a physican. See package insert.

Cautions:Do not add supplementary medication. Check for minute leaks by

squeezing bag firmly. If leaks are found discard bag as sterility may be

impaired. Do not use in series connections. Do not use unless solution is

clear.

Recommended Storage:Store at 25°C (77°F) with excursions permitted

between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room

Temperature]. Do not freeze. Protect from light during storage.

TFB0.05-100CTNR001

Manufactured in the UK for:

Nexus Pharmaceuticals, Inc.

400 Knightsbridge Parkway

Lincolnshire, IL 60069

NEXUS

PHARMACEUTICALS

In clinical trials, inadvertent overdosage with Tirofiban Hydrochloride Injection occurred in doses up to 2 times the recommended dose for initial infusion doses. Inadvertent overdosage occurred in doses up to 9.8 times the 0.15 mcg/kg/min maintenance infusion rate.

The most frequently reported manifestation of overdosage was bleeding, primarily minor mucocutaneous bleeding events and minor bleeding at the sites of cardiac catheterization [see Warnings and Precautions ( 5.1)].

Overdosage of Tirofiban Hydrochloride Injection should be treated by assessment of the patient's clinical condition and cessation or adjustment of the drug infusion as appropriate.

Tirofiban Hydrochloride can be removed by hemodialysis.

Tirofiban Hydrochloride Injection contains tirofiban hydrochloride, a non-peptide antagonist of the platelet GP IIb/IIIa receptor, which inhibits platelet aggregation.

Tirofiban hydrochloride monohydrate is chemically described as N-(butylsulfonyl)- O-[4-(4-piperidinyl)butyl]-L-tyrosine monohydrochloride monohydrate.

Its molecular formula is C ₂₂H ₃₆N ₂O ₅S•HCl•H ₂O and its structural formula is:

Tirofiban hydrochloride monohydrate is a white to off-white, non-hygroscopic, free-flowing powder, with a molecular weight of 495.08. It is very slightly soluble in water.

Tirofiban Hydrochloride Injection Premixed is supplied as a sterile solution in water for injection, for intravenous use. The pH of the solution ranges from 5.5 to 6.5 adjusted with hydrochloric acid and/or sodium hydroxide.

Each 100 mL of the premixed, isosmotic intravenous injection contains 5.618 mg tirofiban hydrochloride monohydrate equivalent to 5 mg tirofiban (50 mcg/mL) and the following inactive ingredients: 0.9 g sodium chloride, 54 mg sodium citrate dihydrate, and 3.5 mg citric acid monohydrate.

Each 250 mL of the premixed, isosmotic intravenous injection contains 14.045 mg tirofiban hydrochloride monohydrate equivalent to 12.5 mg tirofiban (50 mcg/mL) and the following inactive ingredients: 2.25 g sodium chloride, 135 mg sodium citrate dihydrate, and 8.75 mg citric acid monohydrate.

Safety and effectiveness in pediatric patients have not been established.

Of the total number of patients in controlled clinical studies of Tirofiban Hydrochloride Injection, 43% were 65 years and over, while 12% were 75 years and over. With respect to efficacy, the effect of Tirofiban Hydrochloride Injection in the elderly (≥ 65 years) appeared similar to that seen in younger patients (< 65 years). Elderly patients receiving Tirofiban Hydrochloride Injection with heparin or heparin alone had a higher incidence of bleeding complications than did younger patients, but the incremental risk of bleeding in patients treated with Tirofiban Hydrochloride Injection in combination with heparin compared to the risk in patients treated with heparin alone was similar regardless of age. No dose adjustment is recommended for the elderly population [see Dosage and Administration ( 2)] .

For intravenous use only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

To open the 100 mL or the 250 mL premixed bag, first tear off its foil overpouch and remove inner overwrap. The plastic may be somewhat opaque because of moisture absorption during sterilization; the opacity will diminish gradually. Check for leaks by squeezing the inner bag firmly; if any leaks are found or sterility is suspect then the solution should be discarded. Do not use unless the solution is clear and the seal is intact.

Two large-scale clinical studies established the efficacy of Tirofiban Hydrochloride in the treatment of patients with NSTE-ACS (unstable angina/non-ST elevation MI). The two studies examined Tirofiban Hydrochloride alone and added to heparin, prior to and after percutaneous coronary revascularization (if indicated) (PRISM-PLUS) and in comparison to heparin in a similar population (PRISM). These trials are discussed in detail below.

Tirofiban Hydrochloride Injection is contraindicated in patients with:

• Severe hypersensitivity reaction to Tirofiban Hydrochloride Injection (i.e., anaphylactic reactions) [see Adverse Reactions ( 6.2)] .
• A history of thrombocytopenia following prior exposure to Tirofiban Hydrochloride Injection [see Adverse Reactions ( 6.1)] .
• Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month [see Adverse Reactions ( 6.1)] .

Bleeding is the most commonly reported adverse reaction. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Lambda Therapeutics Limited at 1-855-642-2594 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.

Profound thrombocytopenia has been reported with Tirofiban Hydrochloride Injection. Monitor platelet counts beginning about 6 hours after treatment initiation and daily thereafter. If the platelet count decreases to < 90,000/mm ³, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue Tirofiban Hydrochloride Injection and heparin. Previous exposure to a glycoprotein (GP) IIb/IIIa receptor antagonist may increase the risk of developing thrombocytopenia [see Adverse Reactions ( 6.1)] .

Tirofiban Hydrochloride inhibits platelet function, as demonstrated by its ability to inhibit ex vivoadenosine phosphate (ADP)-induced platelet aggregation and prolong bleeding time in healthy subjects and patients with coronary artery disease. The time course of inhibition parallels the plasma concentration profile of the drug.

Following discontinuation of an infusion of Tirofiban Hydrochloride 0.10 mcg/kg/min, ex vivoplatelet aggregation returns to near baseline in 4 to 8 hours in approximately 90% of patients with coronary artery disease. The addition of heparin to this regimen does not significantly alter the percentage of subjects with > 70% inhibition of platelet aggregation (IPA), but does increase the average bleeding time, as well as the number of patients with bleeding times prolonged to > 30 minutes. Similar platelet aggregation recovery rates are observed following discontinuation of a 0.15 mcg/kg/min infusion.

Tirofiban hydrochloride has a half-life of approximately 2 hours. 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. Metabolism appears to be limited.

Tirofiban hydrochloride is not highly bound to plasma proteins and protein binding is concentration independent over the range of 0.01 to 25 mcg/mL. The unbound fraction in human plasma is 35%. The steady state volume of distribution of tirofiban ranges from 22 to 42 liters.

In healthy subjects, the plasma clearance of tirofiban hydrochloride ranges from 213 to 314 mL/min. Renal clearance accounts for 39 to 69% of plasma clearance.

The recommended dosage is 25 mcg/kg administered intravenously within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours.

Tirofiban Hydrochloride Injection 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).

Patients with moderate to severe renal insufficiency have decreased plasma clearance of Tirofiban Hydrochloride. Reduce the dosage of Tirofiban Hydrochloride Injection in patients with severe renal insufficiency [see Dosage and Administration ( 2.3) and Clinical Pharmacology ( 12.3)] .

Safety and efficacy of Tirofiban Hydrochloride Injection has not been established in patients on hemodialysis.

Tirofiban Hydrochloride is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, Tirofiban Hydrochloride inhibits ex vivoplatelet aggregation in a dose- and concentration-dependent manner.

When given according to the PRISM-PLUS regimen of 0.4 mcg/kg/min over 30 minutes followed by a 0.1 mcg/kg/min maintenance infusion, > 90% inhibition of platelet aggregation is attained by the end of the 30-minute infusion. When given according to the recommended regimen of 25 mcg/kg followed by a 0.15 mcg/kg/min maintenance infusion, > 90% inhibition of platelet aggregation is attained within 10 minutes. Platelet aggregation inhibition is reversible following cessation of the infusion of Tirofiban Hydrochloride.

• Tirofiban Hydrochloride Injection can cause serious bleeding. If bleeding cannot be controlled discontinue Tirofiban Hydrochloride Injection. ( 5.1)
• Thrombocytopenia: Discontinue Tirofiban Hydrochloride Injection and heparin. ( 5.2)

• Administer intravenously 25 mcg/kg within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours. In patients with creatinine clearance ≤ 60 mL/min, give 25 mcg/kg within 5 minutes and then 0.075 mcg/kg/min. ( 2)

Tirofiban Hydrochloride Injection is a clear, non-preserved, colorless, isosmotic, sterile premixed injection with sodium chloride for tonicity adjustment available in the following presentations:

Bleeding is the most common complication encountered during therapy with Tirofiban Hydrochloride Injection. Most bleeding associated with Tirofiban Hydrochloride Injection occurs at the arterial access site for cardiac catheterization. Minimize the use of traumatic or potentially traumatic procedures such as arterial and venous punctures, intramuscular injections, nasotracheal intubation, etc.

Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In the PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management), PRISM-PLUS (Platelet Receptor Inhibition for Ischemic Syndrome Management — Patients Limited by Unstable Signs and Symptoms) and RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) trials, 1946 patients received Tirofiban Hydrochloride Injection in combination with heparin and 2002 patients received Tirofiban Hydrochloride Injection alone for about 3 days. Forty-three percent of the population was > 65 years of age and approximately 30% of patients were female. In clinical studies with the recommended regimen (25 mcg/kg bolus followed by a 0.15 mcg/kg/min maintenance infusion), Tirofiban Hydrochloride Injection was administered in combination with aspirin, clopidogrel and heparin or bivalirudin to over 8000 patients for typically ≤ 24 hours. Approximately 30% of the population was > 65 years of age and approximately 25% were female.

The following additional adverse reactions have been identified during post-approval use of Tirofiban Hydrochloride Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.

• Renal Insufficiency: Reduce the dose in patients with severe renal insufficiency. ( 8.6)

Advise patients to watch closely for any signs of bleeding or bruising and to report these to their health care provider when they occur.

Advise patients to discuss with their health care provider their use of any other medications, including over-the-counter or herbal products prior to Tirofiban Hydrochloride Injection use.

Tirofiban Hydrochloride Injection is manufactured in the UK for Nexus Pharmaceuticals, LLC

Lincolnshire, IL 60069

TFBPI02GBR02

NEXUS

PHARMACEUTICALS

Tirofiban Hydrochloride Injection is supplied as a clear, non-preserved, colorless, isosmotic, sterile premixed solution with sodium chloride for tonicity adjustment.

FOR INTRAVENOUS USE ONLY

Store Tirofiban Hydrochloride Injection at controlled room temperature, 25 °C (77 °F) with excursions permitted between 15–30 °C (59–86 °F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light during storage.

The recommended dosage in patients with CrCl ≤ 60 mL/min (calculated using the Cockcroft-Gault equation with actual body weight) is 25 mcg/kg intravenously within 5 minutes and then 0.075 mcg/kg/min, for up to 18 hours.

The recommended infusion rate for patients with CrCl ≤ 60 mL/min using the 100 mL or 250 mL premixed bag can be calculated using the following equation:

The carcinogenic potential of Tirofiban Hydrochloride Injection has not been evaluated.

Tirofiban HCl was negative in the in vitromicrobial mutagenesis and V-79 mammalian cell mutagenesis assays. In addition, there was no evidence of direct genotoxicity in the in vitroalkaline elution and in vitrochromosomal aberration assays. There was no induction of chromosomal aberrations in bone marrow cells of male mice after the administration of intravenous doses up to 5 mg tirofiban/kg (about 3 times the maximum recommended daily human dose when compared on a body surface area basis).

Fertility and reproductive performance were not affected in studies with male and female rats given intravenous doses of tirofiban hydrochloride up to 5 mg/kg/day (about 5 times the maximum recommended daily human dose when compared on a body surface area basis).

Administration Instructions

• Withdraw the bolus dose of Tirofiban Hydrochloride Injection from the 100 mL or 250 mL premixed bag into a syringe. Do not dilute. Administer the bolus dose within 5 minutes via a syringe or IV pump.
• Immediately following the bolus dose administration, administer the maintenance infusion from the 100 mL or 250 mL premixed bag via an IV pump.
• Discard any unused portion left in the bag.

The recommended bolus volume using the 100 mL or 250 mL premixed bag can be calculated using the following equation:

The recommended infusion rate for patients with CrCl (Creatinine Clearance) > 60 mL/min using the 100 mL or 250 mL premixed bag can be calculated using the following equation:

Example calculation of infusion rate for 60 kg patient with CrCl > 60 mL/min using the 100 mL or 250 mL premixed bag:

Principal Display Panel – 100 mL Carton Label

NDC 14789-101-02

PROTECT FROM LIGHT DURING STORAGE

RECOMMENDED FOR USE WITH CALIBRATED INFUSION DEVICE

PREMIXED INJECTION

Tirofiban Hydrochloride

Injection

5 mg per 100 mL (50 mcg per mL)

100 mL

Single-dose Container

Rx Only

Iso-osmotic

Sterile Nonpyrogenic

Each 100mL contains:Tirofiban hydrochloride equivalent to 5 mg tirofiban,

0.9 g sodium chloride, 54 mg sodium citrate dihydrate, 3.5 mg citric acid

monohydrate, Water for Injection. pH may have been adjusted with

hydrochloric acid and/or sodium hydroxide.

Usual Dosage:Intravenously as directed by a physican. See package insert.

Cautions:Do not add supplementary medication. Check for minute leaks by

squeezing bag firmly. If leaks are found discard bag as sterility may be

impaired. Do not use in series connections. Do not use unless solution is

clear.

Recommended Storage:Store at 25°C (77°F) with excursions permitted

between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room

Temperature]. Do not freeze. Protect from light during storage.

TFB0.05-100CTNR001

Manufactured in the UK for:

Nexus Pharmaceuticals, Inc.

400 Knightsbridge Parkway

Lincolnshire, IL 60069

NEXUS

PHARMACEUTICALS

In clinical trials, inadvertent overdosage with Tirofiban Hydrochloride Injection occurred in doses up to 2 times the recommended dose for initial infusion doses. Inadvertent overdosage occurred in doses up to 9.8 times the 0.15 mcg/kg/min maintenance infusion rate.

The most frequently reported manifestation of overdosage was bleeding, primarily minor mucocutaneous bleeding events and minor bleeding at the sites of cardiac catheterization [see Warnings and Precautions ( 5.1)].

Overdosage of Tirofiban Hydrochloride Injection should be treated by assessment of the patient's clinical condition and cessation or adjustment of the drug infusion as appropriate.

Tirofiban Hydrochloride can be removed by hemodialysis.

Tirofiban Hydrochloride Injection contains tirofiban hydrochloride, a non-peptide antagonist of the platelet GP IIb/IIIa receptor, which inhibits platelet aggregation.

Tirofiban hydrochloride monohydrate is chemically described as N-(butylsulfonyl)- O-[4-(4-piperidinyl)butyl]-L-tyrosine monohydrochloride monohydrate.

Its molecular formula is C ₂₂H ₃₆N ₂O ₅S•HCl•H ₂O and its structural formula is:

Tirofiban hydrochloride monohydrate is a white to off-white, non-hygroscopic, free-flowing powder, with a molecular weight of 495.08. It is very slightly soluble in water.

Tirofiban Hydrochloride Injection Premixed is supplied as a sterile solution in water for injection, for intravenous use. The pH of the solution ranges from 5.5 to 6.5 adjusted with hydrochloric acid and/or sodium hydroxide.

Each 100 mL of the premixed, isosmotic intravenous injection contains 5.618 mg tirofiban hydrochloride monohydrate equivalent to 5 mg tirofiban (50 mcg/mL) and the following inactive ingredients: 0.9 g sodium chloride, 54 mg sodium citrate dihydrate, and 3.5 mg citric acid monohydrate.

Each 250 mL of the premixed, isosmotic intravenous injection contains 14.045 mg tirofiban hydrochloride monohydrate equivalent to 12.5 mg tirofiban (50 mcg/mL) and the following inactive ingredients: 2.25 g sodium chloride, 135 mg sodium citrate dihydrate, and 8.75 mg citric acid monohydrate.

Safety and effectiveness in pediatric patients have not been established.

Of the total number of patients in controlled clinical studies of Tirofiban Hydrochloride Injection, 43% were 65 years and over, while 12% were 75 years and over. With respect to efficacy, the effect of Tirofiban Hydrochloride Injection in the elderly (≥ 65 years) appeared similar to that seen in younger patients (< 65 years). Elderly patients receiving Tirofiban Hydrochloride Injection with heparin or heparin alone had a higher incidence of bleeding complications than did younger patients, but the incremental risk of bleeding in patients treated with Tirofiban Hydrochloride Injection in combination with heparin compared to the risk in patients treated with heparin alone was similar regardless of age. No dose adjustment is recommended for the elderly population [see Dosage and Administration ( 2)] .

For intravenous use only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

To open the 100 mL or the 250 mL premixed bag, first tear off its foil overpouch and remove inner overwrap. The plastic may be somewhat opaque because of moisture absorption during sterilization; the opacity will diminish gradually. Check for leaks by squeezing the inner bag firmly; if any leaks are found or sterility is suspect then the solution should be discarded. Do not use unless the solution is clear and the seal is intact.

Two large-scale clinical studies established the efficacy of Tirofiban Hydrochloride in the treatment of patients with NSTE-ACS (unstable angina/non-ST elevation MI). The two studies examined Tirofiban Hydrochloride alone and added to heparin, prior to and after percutaneous coronary revascularization (if indicated) (PRISM-PLUS) and in comparison to heparin in a similar population (PRISM). These trials are discussed in detail below.

Tirofiban Hydrochloride Injection is contraindicated in patients with:

• Severe hypersensitivity reaction to Tirofiban Hydrochloride Injection (i.e., anaphylactic reactions) [see Adverse Reactions ( 6.2)] .
• A history of thrombocytopenia following prior exposure to Tirofiban Hydrochloride Injection [see Adverse Reactions ( 6.1)] .
• Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month [see Adverse Reactions ( 6.1)] .

Bleeding is the most commonly reported adverse reaction. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Lambda Therapeutics Limited at 1-855-642-2594 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.

Profound thrombocytopenia has been reported with Tirofiban Hydrochloride Injection. Monitor platelet counts beginning about 6 hours after treatment initiation and daily thereafter. If the platelet count decreases to < 90,000/mm ³, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue Tirofiban Hydrochloride Injection and heparin. Previous exposure to a glycoprotein (GP) IIb/IIIa receptor antagonist may increase the risk of developing thrombocytopenia [see Adverse Reactions ( 6.1)] .

Tirofiban Hydrochloride inhibits platelet function, as demonstrated by its ability to inhibit ex vivoadenosine phosphate (ADP)-induced platelet aggregation and prolong bleeding time in healthy subjects and patients with coronary artery disease. The time course of inhibition parallels the plasma concentration profile of the drug.

Following discontinuation of an infusion of Tirofiban Hydrochloride 0.10 mcg/kg/min, ex vivoplatelet aggregation returns to near baseline in 4 to 8 hours in approximately 90% of patients with coronary artery disease. The addition of heparin to this regimen does not significantly alter the percentage of subjects with > 70% inhibition of platelet aggregation (IPA), but does increase the average bleeding time, as well as the number of patients with bleeding times prolonged to > 30 minutes. Similar platelet aggregation recovery rates are observed following discontinuation of a 0.15 mcg/kg/min infusion.

Tirofiban hydrochloride has a half-life of approximately 2 hours. 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. Metabolism appears to be limited.

Tirofiban hydrochloride is not highly bound to plasma proteins and protein binding is concentration independent over the range of 0.01 to 25 mcg/mL. The unbound fraction in human plasma is 35%. The steady state volume of distribution of tirofiban ranges from 22 to 42 liters.

In healthy subjects, the plasma clearance of tirofiban hydrochloride ranges from 213 to 314 mL/min. Renal clearance accounts for 39 to 69% of plasma clearance.

The recommended dosage is 25 mcg/kg administered intravenously within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours.

Tirofiban Hydrochloride Injection 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).

Patients with moderate to severe renal insufficiency have decreased plasma clearance of Tirofiban Hydrochloride. Reduce the dosage of Tirofiban Hydrochloride Injection in patients with severe renal insufficiency [see Dosage and Administration ( 2.3) and Clinical Pharmacology ( 12.3)] .

Safety and efficacy of Tirofiban Hydrochloride Injection has not been established in patients on hemodialysis.

Tirofiban Hydrochloride is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, Tirofiban Hydrochloride inhibits ex vivoplatelet aggregation in a dose- and concentration-dependent manner.

When given according to the PRISM-PLUS regimen of 0.4 mcg/kg/min over 30 minutes followed by a 0.1 mcg/kg/min maintenance infusion, > 90% inhibition of platelet aggregation is attained by the end of the 30-minute infusion. When given according to the recommended regimen of 25 mcg/kg followed by a 0.15 mcg/kg/min maintenance infusion, > 90% inhibition of platelet aggregation is attained within 10 minutes. Platelet aggregation inhibition is reversible following cessation of the infusion of Tirofiban Hydrochloride.

• Tirofiban Hydrochloride Injection can cause serious bleeding. If bleeding cannot be controlled discontinue Tirofiban Hydrochloride Injection. ( 5.1)
• Thrombocytopenia: Discontinue Tirofiban Hydrochloride Injection and heparin. ( 5.2)

• Administer intravenously 25 mcg/kg within 5 minutes and then 0.15 mcg/kg/min for up to 18 hours. In patients with creatinine clearance ≤ 60 mL/min, give 25 mcg/kg within 5 minutes and then 0.075 mcg/kg/min. ( 2)

Tirofiban Hydrochloride Injection is a clear, non-preserved, colorless, isosmotic, sterile premixed injection with sodium chloride for tonicity adjustment available in the following presentations:

Bleeding is the most common complication encountered during therapy with Tirofiban Hydrochloride Injection. Most bleeding associated with Tirofiban Hydrochloride Injection occurs at the arterial access site for cardiac catheterization. Minimize the use of traumatic or potentially traumatic procedures such as arterial and venous punctures, intramuscular injections, nasotracheal intubation, etc.

Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In the PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management), PRISM-PLUS (Platelet Receptor Inhibition for Ischemic Syndrome Management — Patients Limited by Unstable Signs and Symptoms) and RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) trials, 1946 patients received Tirofiban Hydrochloride Injection in combination with heparin and 2002 patients received Tirofiban Hydrochloride Injection alone for about 3 days. Forty-three percent of the population was > 65 years of age and approximately 30% of patients were female. In clinical studies with the recommended regimen (25 mcg/kg bolus followed by a 0.15 mcg/kg/min maintenance infusion), Tirofiban Hydrochloride Injection was administered in combination with aspirin, clopidogrel and heparin or bivalirudin to over 8000 patients for typically ≤ 24 hours. Approximately 30% of the population was > 65 years of age and approximately 25% were female.

The following additional adverse reactions have been identified during post-approval use of Tirofiban Hydrochloride Injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to the drug exposure.

• Renal Insufficiency: Reduce the dose in patients with severe renal insufficiency. ( 8.6)

Advise patients to watch closely for any signs of bleeding or bruising and to report these to their health care provider when they occur.

Advise patients to discuss with their health care provider their use of any other medications, including over-the-counter or herbal products prior to Tirofiban Hydrochloride Injection use.

Tirofiban Hydrochloride Injection is manufactured in the UK for Nexus Pharmaceuticals, LLC

Lincolnshire, IL 60069

TFBPI02GBR02

NEXUS

PHARMACEUTICALS

Tirofiban Hydrochloride Injection is supplied as a clear, non-preserved, colorless, isosmotic, sterile premixed solution with sodium chloride for tonicity adjustment.

FOR INTRAVENOUS USE ONLY

Store Tirofiban Hydrochloride Injection at controlled room temperature, 25 °C (77 °F) with excursions permitted between 15–30 °C (59–86 °F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light during storage.

The recommended dosage in patients with CrCl ≤ 60 mL/min (calculated using the Cockcroft-Gault equation with actual body weight) is 25 mcg/kg intravenously within 5 minutes and then 0.075 mcg/kg/min, for up to 18 hours.

The recommended infusion rate for patients with CrCl ≤ 60 mL/min using the 100 mL or 250 mL premixed bag can be calculated using the following equation:

The carcinogenic potential of Tirofiban Hydrochloride Injection has not been evaluated.

Tirofiban HCl was negative in the in vitromicrobial mutagenesis and V-79 mammalian cell mutagenesis assays. In addition, there was no evidence of direct genotoxicity in the in vitroalkaline elution and in vitrochromosomal aberration assays. There was no induction of chromosomal aberrations in bone marrow cells of male mice after the administration of intravenous doses up to 5 mg tirofiban/kg (about 3 times the maximum recommended daily human dose when compared on a body surface area basis).

Fertility and reproductive performance were not affected in studies with male and female rats given intravenous doses of tirofiban hydrochloride up to 5 mg/kg/day (about 5 times the maximum recommended daily human dose when compared on a body surface area basis).