FDA Label for Tirofiban

1 Indications And Usage

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).

2.1 Recommended Dosage

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

2.2 Administration

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 250 mL premixed bag, first tear off its foil overpouch. 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.

Administration Instructions

• The bolus dose of tirofiban hydrochloride injection may be administered from the 100 mL or 250 mL premixed bag. Do not dilute. Administer the bolus dose within 5 minutes via IV pump.
• Immediately following the bolus dose administration, administer the maintenance infusion from the 100 mL premixed bag or the 250 mL premixed bag via an IV pump.
• Discard any unused portion left in the bag.

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

                                                                                  Bolus Volume        =          25 mcg/kg x body weight (kg)
                                                                                            (mL)                                         50 mcg/mL


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




                                                                      Infusion Rate for CrCl > 60 mL/min  =  0.15 mcg/kg/min × body weight (kg) × 60 min/h
                                                                                           (mL/h)                                                            50 mcg/mL

  




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




                                                                     Infusion Rate for CrCl > 60 mL/min  =  0.15 mcg/kg/min × 60 kg × 60 min/h  =  10.8 mL/h
                                                                                              (mL/h)                                                          50 mcg/mL




Drug Compatibilities

Tirofiban hydrochloride injection can be administered in the same intravenous line as heparin, atropine sulfate, dobutamine, dopamine, epinephrine hydrochloride (HCl), famotidine injection, furosemide, lidocaine, midazolam HCl, morphine sulfate, nitroglycerin, potassium chloride, and propranolol HCl. Do not administer tirofiban hydrochloride injection through the same IV line as diazepam. Do not add other drugs or remove solution directly from the bag with a syringe.

2.3 Dose Adjustment For Renal Impairment

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 premixed bag or 250 mL premixed bag can be calculated using the following equation:

                                                                         Infusion Rate for CrCl ≤ 60 mL/min  =  0.075 mcg/kg/min × body weight (kg) × 60 min/h 
                                                                                   (mL/h)                                                       50 mcg/mL

3 Dosage Forms And Strengths

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

4 Contraindications

Tirofiban hydrochloride injection is contraindicated in patients with:

• Severe hypersensitivity reaction to tirofiban hydrochloride (i.e., anaphylactic reactions) [see Adverse Reactions (6.2)].
• A history of thrombocytopenia following prior exposure to tirofiban hydrochloride [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)].

5.1 General Risk Of Bleeding

Bleeding is the most common complication encountered during therapy with tirofiban hydrochloride. Most bleeding associated with tirofiban hydrochloride 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.

5.2 Thrombocytopenia

Profound thrombocytopenia has been reported with tirofiban hydrochloride. Monitor platelet counts beginning about 6 hours after treatment initiation and daily thereafter. If the platelet count decreases to < 90,000/mm³, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue tirofiban hydrochloride and heparin. Previous exposure to a glycoprotein (GP) IIb/IIIa receptor antagonist may increase the risk of developing thrombocytopenia [see Adverse Reactions (6.1)].

6.1 Clinical Trial Experience

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 in combination with heparin and 2002 patients received tirofiban hydrochloride 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 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.

Bleeding

PRISM-PLUS Regimen

The incidences of major and minor bleeding using the TIMI criteria in the PRISM-PLUS study are shown below.

The incidence rates of TIMI major bleeding in patients undergoing percutaneous procedures in PRISM- PLUS are shown below. 

The incidence rates of TIMI major bleeding in patients undergoing coronary artery bypass graft surgery (CABG) in PRISM-PLUS within one day of discontinuation of tirofiban hydrochloride were 17% on tirofiban hydrochloride plus heparin (N=29) and 35% on heparin alone (N=31).

Recommended (“High-Dose Bolus”) Regimen

Rates of major bleeds (including any intracranial, intraocular or retroperitoneal hemorrhage, clinically overt signs of hemorrhage associated with a drop in hemoglobin of > 3 g/dL or any drop in hemoglobin by 4 g/dL, bleeding requiring transfusion of ≥ 2 U blood products, bleeding directly resulting in death within 7 days or hemodynamic compromise requiring intervention) were consistent with the rates observed in subjects administered the PRISM-PLUS regimen of tirofiban hydrochloride. There was a trend toward greater bleeding in ST segment elevation myocardial infarction (STEMI) patients treated with fibrinolytics prior to administration of tirofiban hydrochloride using the recommended regimen during rescue PCI.

Non-Bleeding

The incidences of non-bleeding adverse events that occurred at an incidence of > 1% and numerically higher than control, regardless of drug relationship, are shown below:

Thrombocytopenia

Patients treated with tirofiban hydrochloride plus heparin, were more likely to experience decreases in platelet counts than were those on heparin alone. These decreases were reversible upon discontinuation of tirofiban hydrochloride. The percentage of patients with a decrease of platelets to < 90,000/mm³ was 1.5%, compared with 0.6% in the patients who received heparin alone. The percentage of patients with a decrease of platelets to < 50,000/mm³ was 0.3%, compared with 0.1% of the patients who received heparin alone.

6.2 Post-Marketing Experience

The following additional adverse reactions have been identified during post-approval use of tirofiban hydrochloride. 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.

Hypersensitivity: Severe allergic reactions including anaphylactic reactions have occurred during the first day of tirofiban hydrochloride infusion, during initial treatment, and during readministration of tirofiban hydrochloride. Some cases have been associated with severe thrombocytopenia (platelet counts < 10,000/mm³). No information is available on the formation of antibodies to tirofiban.

7 Drug Interactions

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

8.1 Pregnancy

Risk Summary

While published data cannot definitively establish the absence of risk, available published case reports have not established an association with tirofiban use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant woman and fetus (see Clinical Considerations). Studies with tirofiban HCl at intravenous doses up to 5 mg/kg/day (about 5 and 13 times the maximum recommended daily human dose for rat and rabbit, respectively, when compared on a body surface area basis) have revealed no harm to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Myocardial infarction is a medical emergency in pregnancy which can be fatal to the pregnant woman and fetus if left untreated.

Data

Animal Data

There was no evidence of maternal or developmental toxicity in any of the studies in Table 5.

8.2 Lactation

Risk Summary

There is no data on the presence of tirofiban in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on human milk production. However, tirofiban is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tirofiban hydrochloride and any potential adverse effects on the breastfed child from tirofiban hydrochloride or from the underlying maternal condition.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Of the total number of patients in controlled clinical studies of tirofiban hydrochloride, 43% were 65 years and over, while 12% were 75 years and over. With respect to efficacy, the effect of tirofiban hydrochloride in the elderly (≥ 65 years) appeared similar to that seen in younger patients (< 65 years). Elderly patients receiving tirofiban hydrochloride 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 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)].

8.6 Renal Insufficiency

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

Safety and efficacy of tirofiban hydrochloride has not been established in patients on hemodialysis.

10 Overdosage

In clinical trials, inadvertent overdosage with tirofiban hydrochloride 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 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.

11 Description

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 hydrochloride monohydrate.

Its molecular formula is C₂₂H₃₆N₂O₅S•HCl•H₂O and its structural formula is:

chemical-structure - tirofiban str

Tirofiban hydrochloride monohydrate is a off-white, non-hygroscopic, free-flowing powder, with a molecular weight of 495.07. 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 3.2 mg citric acid anhydrous.

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 mg citric acid anhydrous.

12.1 Mechanism Of Action

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 vivo platelet 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.

12.2 Pharmacodynamics

Tirofiban hydrochloride inhibits platelet function, as demonstrated by its ability to inhibit ex vivo adenosine 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 vivo platelet 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.

12.3 Pharmacokinetics

Tirofiban 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 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 ranges from 213 to 314 mL/min. Renal clearance accounts for 39 to 69% of plasma clearance.

Specific Populations  

There is no effect on clearance of tirofiban by sex, race, age, or hepatic impairment.

Renal Insufficiency

Plasma clearance of tirofiban is decreased about 40% in subjects with creatinine clearance < 60 mL/min and > 50% in patients with creatinine clearance < 30 mL/min, including patients requiring hemodialysis [see Dosage and Administration (2.3)]. Tirofiban is removed by hemodialysis.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

The carcinogenic potential of tirofiban hydrochloride has not been evaluated.

Tirofiban HCl was negative in the in vitro microbial mutagenesis and V-79 mammalian cell mutagenesis assays. In addition, there was no evidence of direct genotoxicity in the in vitro alkaline elution and in vitro chromosomal 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 up to 5 mg/kg/day (about 5 times the maximum recommended daily human dose when compared on a body surface area basis).

14 Clinical Studies

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.

PRISM-PLUS (Platelet Receptor Inhibition for Ischemic Syndrome Management — Patients Limited by Unstable Signs and Symptoms)

In the double-blind PRISM-PLUS trial, 1570 patients with documented NSTE-ACS within 12 hours of entry into the study were randomized to tirofiban hydrochloride (30 minute initial infusion of 0.4 mcg/kg/min followed by a maintenance infusion of 0.10 mcg/kg/min) in combination with heparin (bolus of 5,000 U followed by an infusion of 1,000 U/h titrated to maintain an activated partial thromboplastin time (APTT) of approximately 2 times control) or to heparin alone. All patients received concomitant aspirin unless contraindicated. Patients who were medically managed or who underwent revascularization procedures were studied. Patients underwent 48 hours of medical stabilization on study drug therapy, and they were to undergo angiography before 96 hours (and, if indicated, angioplasty/atherectomy, while continuing on tirofiban hydrochloride and heparin for 12 to 24 hours after the procedure). Tirofiban hydrochloride and heparin could be continued for up to 108 hours. Exclusions included contraindications to anticoagulation, decompensated heart failure, platelet count < 150,000/mm³, and serum creatinine > 2.5 mg/dL. The mean age of the population was 63 years; 32% of patients were female and approximately half of the population presented with non-ST elevation myocardial infarction. On average, patients received tirofiban hydrochloride for 71 hours.

A third group of patients was initially randomized to tirofiban hydrochloride alone (no heparin). This arm was stopped when the group was found, at an interim look, to have greater mortality than the other two groups.

The primary endpoint of the study was a composite of refractory ischemia, new MI and death within 7 days. There was a 32% risk reduction in the overall composite primary endpoint. The components of the composite were examined separately and the results are shown in Table 6. Note that the sum of the individual components may be greater than the composite (if a patient experiences multiple component events only one event counts towards the composite). 

The benefit seen at 7 days was maintained over time. The risk reduction in the composite endpoint at 30 days and 6 months is shown in the Kaplan-Meier curve below.

tirofiban-figure-1 - tirofiban fig1

An analysis of the results by sex suggests that women who are medically managed or who undergo subsequent percutaneous transluminal coronary angioplasty (PTCA)/atherectomy may receive less benefit from tirofiban hydrochloride (95% confidence limits for relative risk of 0.61 to 1.74) than do men (0.43 to 0.89) (p=0.11). This difference may be a true treatment difference, the effect of other differences in these subgroups, or a chance occurrence.

Approximately 90% of patients in the PRISM-PLUS study underwent coronary angiography and 30% underwent angioplasty/atherectomy during the first 30 days of the study. The majority of these patients continued on study drug throughout these procedures. Tirofiban hydrochloride was continued for 12 to 24 hours (average 15 hours) after angioplasty/atherectomy. The effects of tirofiban hydrochloride at Day 30 did not appear to differ among sub-populations that did or did not receive PTCA or CABG, both prior to and after the procedure.

PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management)

In the PRISM study, a randomized, parallel, double-blind study, 3232 patients with NSTE-ACS intended to be managed without coronary intervention were randomized to tirofiban hydrochloride (initial dose of 0.6 mcg/kg/min for 30 minutes followed by 0.15 mcg/kg/min for 47.5 hours) or heparin (5,000-unit intravenous bolus followed by an infusion of 1,000 U/h for 48 hours). The mean age of the population was 62 years; 32% of the population was female and 25% had non-ST elevation MI on presentation. Thirty percent had no ECG evidence of cardiac ischemia. Exclusion criteria were similar to PRISM-PLUS. The primary endpoint was the composite endpoint of refractory ischemia, MI or death at the end of the 48-hour drug infusion. The results are shown in Table 7.

In the PRISM study, no adverse effect of tirofiban hydrochloride on mortality at either 7 or 30 days was detected. This result is different from that in the PRISM-PLUS study, where the arm that included tirofiban hydrochloride without heparin (N=345) was dropped at an interim analysis by the Data Safety Monitoring Committee for increased mortality at 7 days.

16 How Supplied/Storage And Handling

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° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze. Protect from light during storage.

Discard Unused Portion.

17 Patient Counseling Information

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 use.

Distributed by:
Eugia US LLC
279 Princeton-Hightstown Rd.
E. Windsor, NJ 08520
 

Manufactured by:
Eugia Pharma Specialities Limited
Hyderabad - 500032
India

Package Label.Principal Display Panel 5 Mg Per 100 Ml (50 Mcg/Ml) - Infusion Bag Label

Recommended for Use With
Calibrated Infusion Device
Rx only       NDC 55150-429-01
Tirofiban
Hydrochloride Injection
5 mg per 100 mL
(50 mcg/mL)
For Intravenous Infusion
Premixed           Iso-osmotic
Sterile, Nonpyrogenic
100 mL Single-Dose Container

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 5 mg per 100 mL (50 mcg/mL) - Infusion Bag Label - tirofiban fig2

Package Label.Principal Display Panel 5 Mg Per 100 Ml (50 Mcg/Ml) - Pouch Label

TO OPEN: TEAR AT NOTCH
Rx only                          NDC 55150-429-01
Protect From Light During Storage
Recommended for Use With Calibrated Infusion Device
Premixed Injection
Tirofiban
Hydrochloride Injection
5 mg per 100 mL
(50 mcg/mL)
For Intravenous Infusion
Sterile, Nonpyrogenic             Iso-osmotic
100 mL Single-Dose Container

Each 100 mL contains: Tirofiban hydrochloride equivalent to 5 mg tirofiban, 900 mg sodium chloride, 54 mg sodium citrate dihydrate, 3.2 mg citric acid anhydrous, Water for Injection. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide.

Usual Dosage: Intravenously as directed by a physician. 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° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Discard unused portion. Do not freeze. Protect from light during storage.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 5 mg per 100 mL (50 mcg/mL) - Pouch Label - tirofiban fig3

Package Label.Principal Display Panel 5 Mg Per 100 Ml (50 Mcg/Ml) - Container Carton

Rx only        NDC 55150-429-01
Protect From Light During Storage
Recommended for Use With Calibrated Infusion Device
Premixed Injection
Tirofiban
Hydrochloride Injection
5 mg per 100 mL
(50 mcg/mL)
For Intravenous Infusion
Sterile, Nonpyrogenic                  Iso-osmotic
100 mL Single-Dose Container
eugia

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 5 mg per 100 mL (50 mcg/mL) - Container Carton - tirofiban fig4

Package Label.Principal Display Panel 12.5 Mg Per 250 Ml (50 Mcg/Ml) - Infusion Bag Label

Recommended for Use With Calibrated Infusion Device
Rx only        NDC 55150-430-01
Tirofiban
Hydrochloride Injection
12.5 mg per 250 mL
(50 mcg/mL)
For Intravenous Infusion
Premixed       Iso-osmotic
Sterile, Nonpyrogenic    250 mL Single-Dose Container

Each 250 mL contains: Tirofiban hydrochloride equivalent to 12.5 mg tirofiban, 2.25 g sodium chloride, 135 mg sodium citrate dihydrate, 8 mg citric acid anhydrous, water for injection. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide.
Usual Dosage: Intravenously as directed by a physician. 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° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Discard unused portion. Do not freeze. Protect from light during storage.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 12.5 mg per 250 mL (50 mcg/mL) - Infusion Bag Label - tirofiban fig5

Package Label.Principal Display Panel 12.5 Mg Per 250 Ml (50 Mcg/Ml) - Pouch Label

TO OPEN: TEAR AT NOTCH
Rx only        NDC 55150-430-01
Protect From Light During Storage
Recommended for Use With Calibrated Infusion Device
Premixed Injection
Tirofiban
Hydrochloride Injection
12.5 mg per 250 mL
(50 mcg/mL)
For Intravenous Infusion
Sterile, Nonpyrogenic        Iso-osmotic
250 mL Single-Dose Container

Each 250 mL contains: Tirofiban hydrochloride equivalent to 12.5 mg tirofiban, 2.25 g sodium chloride, 135 mg sodium citrate dihydrate, 8 mg citric acid anhydrous, water for injection. pH may have been adjusted with hydrochloric acid and/or sodium hydroxide.
Usual Dosage: Intravenously as directed by a physician. 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° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Discard unused portion. Do not freeze. Protect from light during storage.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 12.5 mg per 250 mL (50 mcg/mL) - Pouch Label - tirofiban fig6

Package Label.Principal Display Panel 12.5 Mg Per 250 Ml (50 Mcg/Ml) - Container Carton

Rx only        NDC 55150-430-01
Protect From Light During Storage
Recommended for Use With Calibrated Infusion Device
Premixed Injection
Tirofiban
Hydrochloride Injection
12.5 mg per 250 mL
(50 mcg/mL)
For Intravenous Infusion
Sterile, Nonpyrogenic                     Iso-osmotic
250 mL Single-Dose Container
eugia

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 12.5 mg per 250 mL (50 mcg/mL) - Container Carton - tirofiban fig7