PRODUCT MONOGRAPH

AGGRASTAT(r)

Concentrate for Infusion

(tirofiban hydrochloride for injection) 0.25 mg/mL in 50 mL vials

AGGRASTAT(r)

Solution for Infusion

(tirofiban hydrochloride injection) 5 mg/100 mL in 250 mL and 500 mL bags

ACTIONS AND CLINICAL PHARMACOLOGY

Mechanism of Action

AGGRASTAT(r) (tirofiban hydrochloride) is a reversible non-peptide antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner.

Pharmacodynamics

Tirofiban causes potent inhibition of platelet function as demonstrated by its ability to inhibit ex vivo adenosine phosphate (ADP)-induced platelet aggregation and prolong bleeding time (BT) 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, 0.1 :g/kg/min, ex vivo-platelet aggregation returns to near baseline in approximately 90% of patients with coronary artery disease in 4 to 8 hours. 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. In patients with unstable angina, a two-staged intravenous infusion regimen of tirofiban (loading infusion of 0.4 :g/kg/min for 30 minutes followed by 0.1 :g/kg/min for up to 48 hours in the presence of heparin and ASA), produces approximately 90% inhibition of ex vivo ADP-induced platelet aggregation with a 2.9-fold prolongation of bleeding time during the infusion. Inhibition was achieved rapidly with the 30-minute loading infusion and was maintained over the duration of the infusion.

Pharmacokinetics

In healthy subjects, tirofiban is cleared from the plasma largely by renal excretion, with about 66% of a 14C-labeled tirofiban dose appearing in the urine and about 23% in the feces, mainly as unchanged tirofiban. The metabolism of tirofiban 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 :g/mL. 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. Half-life ranges from 1.4 to 1.8 hours. In patients with coronary artery disease, the plasma clearance of tirofiban ranges from 152 to 267 mL/min. Renal clearance accounts for 39% of plasma clearance. Half-life ranges from 1.9 to 2.2 hours.

Special Populations

Gender

Plasma clearance of tirofiban in patients with coronary artery disease is similar in males and females.

Elderly

Plasma clearance of tirofiban is about 19 to 26% lower in elderly (>65 years) patients with coronary artery disease compared to younger (#65 years) patients.

Race

No difference in plasma clearance was detected in patients of different races.

Renal Insufficiency

Plasma clearance of tirofiban is lower to a clinically significant extent (>50%) in patients with creatinine clearance <30 mL/min, including patients requiring hemodialysis (see DOSAGE AND ADMINISTRATION, Patients with Severe Renal Insufficiency). Tirofiban is removed by hemodialysis.

Clinical Trials

Unstable Angina/Non-Q-Wave Myocardial Infarction

In the multicenter, randomized, parallel, double-blind PRISM-PLUS trial (Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms), the use of AGGRASTAT(r) (tirofiban hydrochloride) in combination with heparin (n=773) versus heparin alone (n=797) was compared in patients with documented unstable angina/non-Q-wave myocardial infarction within 12 hours of the last episode of chest pain before randomization. All patients with unstable angina/non-Q-wave myocardial infarction had cardiac ischemia documented by ECG or had elevated cardiac enzymes. The mean age of the population was 63 years; 32% of patients were female and approximately half of the population presented with non-Q-wave myocardial infarction. Patients were randomized to either AGGRASTAT(r) (30-minute loading infusion of 0.4 :g/kg/min followed by a maintenance infusion of 0.10 :g/kg/min) and heparin (bolus of 5,000 units (U) followed by an infusion of 1,000 U/hr titrated to maintain an activated partial thromboplastin time (aPTT) of approximately 2 times control), or heparin alone (bolus of 5,000 U followed by an infusion of 1,000 U/hr titrated to maintain an aPTT of approximately 2 times control). All patients received concomitant acetylsalicylic acid (ASA) unless contraindicated. Comprehensive Management: Patients underwent 48 hours of medical stabilization on study drug therapy, after which they could undergo angiography and angioplasty (if indicated), while continuing on AGGRASTAT(r). AGGRASTAT(r) was generally administered for a minimum of 48 hours and was continued up to 108 hours; patients received AGGRASTAT(r) for 71.3 hours (average for all patients). The primary endpoint of the study was a composite of refractory ischemia, new myocardial infarction and death at 7 days following initiation of AGGRASTAT(r). At the primary endpoint, there was a 31.6% risk reduction in the overall composite, a 46.6% risk reduction in myocardial infarction, and a 42.8% risk reduction in the composite of myocardial infarction and death. The results are shown in Table 1:

Table 1

Cardiac Ischemic Events (7 Days)

Endpoint AGGRASTAT(r)

Heparin (n=797)

Risk Reduction

p-value

The early clinical benefit seen at 7 days was maintained over time. At 30 days, the risk of the composite endpoint was reduced by 21.8% (p=0.029) and there was a 29.8% (p=0.027) reduction in the composite of myocardial infarction and death. At 6 months, the risk of the composite endpoint was reduced by 18.9% (p=0.024). In addition, there was a 22.5% (p=0.063) risk reduction in the composite of myocardial infarction and death. The risk reduction in the composite endpoint at 7 days, 30 days and 6 months is shown in the Kaplan-Meier curve below. In the PRISM-PLUS study, 90% of patients underwent coronary angiography and 30% underwent angioplasty. The majority of these patients continued on study drug throughout these procedures. AGGRASTAT(r) was continued for 12 - 24 hours (average 15 hours) after angioplasty. Although the benefit of adding tirofiban to heparin was observed in all interventional subgroups used in the management of these patients [Percutaneous Transluminal Coronary Angioplasty (PTCA), Coronary Artery Bypass Graft (CABG) or medical management alone], a pre-specified analysis suggested that there was some amplification of the benefit in patients undergoing PTCA. A sub-study in PRISM-PLUS of angiograms up to 96 hours found that there was a statistically significant decrease in the extent of angiographically apparent thrombus and increase in the blood flow in patients treated with AGGRASTAT(r) in combination with heparin compared to heparin alone. In the PRISM-PLUS study, the benefit of AGGRASTAT(r) was consistent regardless of age or gender.

CONTRAINDICATIONS

AGGRASTAT(r) (tirofiban hydrochloride) is contraindicated in patients with: known hypersensitivity to any component of the product active internal bleeding or a history of bleeding diathesis a history of intracranial hemorrhage or neoplasm, arteriovenous malformation, or aneurysm who developed thrombocytopenia following prior exposure to AGGRASTAT(r) known coagulopathy, platelet disorder or history of thrombocytopenia stroke within 30 days prior to hospitalization or any history of hemorrhagic stroke major surgical procedure or severe physical trauma within the previous month history, symptoms or findings suggestive of aortic dissection severe uncontrolled hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure of >110 mmHg) concomitant use of another GP IIb/IIIa inhibitor acute pericarditis cirrhosis or clinically significant liver disease angina precipitated by obvious provoking factors (e.g., arrhythmia, severe anemia, hyperthyroidism or hypotension) recent epidural procedure

WARNINGS

AGGRASTAT(r) (tirofiban hydrochloride) inhibits platelet aggregation and therefore caution should be employed when used with other drugs affecting hemostasis (see Laboratory Monitoring, Adverse Reactions and Post Marketing Experience).

AGGRASTAT(r) should be used with caution in the following patients: recent (<1 year) bleeding, including a history of gastrointestinal bleeding, or genitourinary bleeding of clinical significance platelet count <150,000 cells/mm3 history of cerebrovascular disease within 1 year hemorrhagic retinopathy chronic hemodialysis (see Dosage and Administration)

Use in Pregnancy

Tirofiban has been shown to cross the placenta in pregnant rats and rabbits. However, there are no adequate and well controlled studies in pregnant women. Tirofiban should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether AGGRASTAT(r) is excreted in human milk. However, significant levels of tirofiban are excreted in rat milk. Therefore, nursing should be discontinued during the period of drug administration and the milk discarded. Nursing may resume 24 hours after cessation of treatment with tirofiban.

Pediatric Use

Safety and effectiveness in children have not been established.

PRECAUTIONS

Bleeding Precautions

AGGRASTAT(r) (tirofiban hydrochloride) inhibits platelet aggregation and therefore caution should be employed when it is used with other drugs that affect hemostasis (e.g., warfarin). The safety of AGGRASTAT(r) when used in combination with thrombolytic agents has not been established. During therapy with AGGRASTAT(r), patients should be monitored for potential bleeding. When bleeding cannot be controlled with pressure, infusion of AGGRASTAT(r) and heparin should be discontinued. Transfusions may be given if required. Fatal bleedings have been reported (see ADVERSE REACTIONS).

Femoral Artery Access Site

AGGRASTAT(r) is associated with minor increases in bleeding rates particularly at the site of arterial access for femoral sheath placement. Care should be taken when attempting vascular access that only the anterior wall of the femoral artery is punctured [a Seldinger (through and through) technique for obtaining sheath access should be avoided]. Arterial sheaths should be removed when the patient's activated clotting time is < 180 sec or 2 - 6 hours following cessation of heparin.

Laboratory Monitoring

Baseline evaluation:

Should be performed on platelet count, hematocrit, hemoglobin and activated partial thromboplastin time (aPTT) prior to treatment.

Following the loading infusion: Monitor platelet count within 6 hours following the loading infusion and at least daily thereafter (or more frequently if there is evidence of significant decline). Acute decrease in platelet count to <20,000 cells/mm3 within one day after start of therapy with AGGRASTAT(r) have been reported post-marketing (see Post Marketing Experience & Thrombocytopenia).

In patients previously exposed to GP IIb/IIIa receptor antagonists:

Monitor platelet count earlier and more often. Platelet decreases have been observed in patients with no prior history of thrombocytopenia upon re- administration of GP IIb/IIIa receptor antagonists (see Post-Marketing Experience).

If the platelet count decreases to <90,000 cells/mm3: (r)

Evaluate to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed discontinue AGGRASTAT

and heparin and treat appropriately.

Monitor aPTT:

Monitor aPTT frequently and adjust the dose of heparin accordingly. Potentially life-threatening bleeding may occur especially when

heparin is administered with other products affecting hemostasis, such as GP IIb/IIIa receptor antagonists (see DOSAGE AND ADMINISTRATION).

Renal Insufficiency

Patients with moderate (creatinine clearance < 60 mL/min) and severe (creatinine clearance < 30 mL/min) renal insufficiency should be monitored for bleeding complications. Since clinical studies showed a decreased plasma clearance of tirofiban in patients with severe renal insufficiency, the dosage should be reduced in these patients (see DOSAGE AND ADMINISTRATION).

Use in the Elderly

In clinical studies the efficacy of AGGRASTAT(r) in the elderly ($65 years) was comparable to that seen in younger patients (<65 years). Elderly patients receiving AGGRASTAT(r) with heparin or heparin alone had a higher incidence of bleeding complications than younger patients.

Drug Interactions

AGGRASTAT(r) has been studied on a background of ASA and heparin. The use of AGGRASTAT(r), in combination with heparin and ASA, has been associated with an increase in bleeding compared to heparin and ASA alone (see ADVERSE REACTIONS). Caution should be employed when AGGRASTAT(r) is used with other drugs that affect hemostasis (e.g., warfarin, ticlopidine) (see WARNINGS and PRECAUTIONS, Bleeding Precautions). AGGRASTAT(r) has been used concomitantly in clinical studies with beta-blockers, calcium-channel blockers, non-steroidal anti-inflammatory agents (NSAIDs) and nitrate preparations without evidence of clinically significant adverse interactions. Pharmacokinetics of AGGRASTAT(r) were not affected by a wide variety of drugs commonly administered to this patient population (e.g., antihypertensives, calcium- channel blockers, beta-blockers, diuretics, antidiabetics, lipid-lowering agents, digitalis preparations, and agents for the control of gastric acidity).

SYMPTOMS AND TREATMENT OF OVERDOSAGE

In clinical trials, inadvertent overdosage with AGGRASTAT(r) (tirofiban hydrochloride) occurred in doses up to 5 times and 2 times the recommended dose for bolus administration and loading infusion, respectively. Inadvertent overdosage occurred in doses up to 9.8 times of the 0.15 :g/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 PRECAUTIONS, Bleeding Precautions). Overdosage of AGGRASTAT(r) should be treated by assessment of the patient's clinical condition and cessation or adjustment of the drug infusion as appropriate. AGGRASTAT(r) is dialyzable.

DOSAGE

DOSAGE AND ADMINISTRATION

Unstable Angina Pectoris or Non-Q-Wave Myocardial Infarction: AGGRASTAT(r) (tirofiban hydrochloride) should be administered intravenously, in combination with heparin, at the initial infusion rate of 0.4 :g/kg/min for 30 minutes. Upon completion of the initial infusion, AGGRASTAT(r) should be continued at a maintenance infusion rate of 0.1 :g/kg/min.

Recommended Length of Infusion

:

For patients who do not exhibit any signs of refractory ischemic symptoms and do not proceed into angiography and angioplasty: at least 48 hours. For patients proceeding into angiography and angioplasty the infusion 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. There are no safety data for total infusion time extended beyond 108 hours.

AGGRASTAT(r) Concentrate for Infusion must first be diluted to the same strength as AGGRASTAT(r) Solution for Infusion as noted under

DIRECTIONS FOR USE.

* Infusion rate based on a final concentration of 50 :g/mL.

Patients With Severe Renal Insufficiency

As specified in the above dosing tables, the dosage of AGGRASTAT(r) should be decreased by 50% in patients with severe renal insufficiency (creatinine clearance <30 mL/min) (see PRECAUTIONS, Renal Insufficiency and PHARMACOLOGY, Pharmacokinetics, Special Populations, Renal Insufficiency).

Other Patient Populations

No dosage adjustment is recommended for elderly patients or female patients.

ADMINISTRATION

AGGRASTAT(r) is for intravenous use only using sterile equipment. AGGRASTAT(r) may be co-administered with heparin through the same line. AGGRASTAT(r) is recommended for use with a calibrated infusion device. Care should be taken to avoid a prolonged loading infusion. In clinical studies, patients received ASA unless contraindicated. AGGRASTAT(r) may be administered in the same intravenous line as atropine sulfate, dobutamine, dopamine, epinephrine HCI, furosemide, lidocaine, midazolam HCI, morphine sulfate, nitroglycerin, PEPCID(r) (famotidine), potassium chloride and propranolol HCI injection.

AGGRASTAT(r) should not be administered in the same intravenous line as diazepam.

CONCENTRATE FOR INFUSION

The vial of AGGRASTAT(r) (concentrate) must be diluted prior to administration (see Directions for Use of AGGRASTAT(r) Concentrate for Infusion).

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Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use, whenever solution and container permit. AGGRASTAT(r) does not require filtration prior to use.

Directions for Use of AGGRASTAT(r) Concentrate for Infusion

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1. Withdraw 50 mL from a 250 mL bag of sterile 0.9% saline or 5% dextrose in water and replace it with 50 mL of AGGRASTAT(r) & Concentrate for Infusion (from one 50 mL vial) to achieve a concentration of 50 :g/mL. Mix well before administration.

2. Administer according to the appropriate dosage adjustments by weight above.

3. Any unused solution should be discarded.

PEPCID(r) is a Registered Trademark of Merck & Co., Inc. Used under license.

SOLUTION FOR INFUSION

Directions for Use of AGGRASTAT(r) Solution for Infusion

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AGGRASTAT(r) & Solution for Infusion, supplied in IntraVia * containers (PL 2408 plastic), is available as a 250 mL or a 500 mL iso-osmotic solution premixed with 0.9% sodium chloride and is stable through the labeled expiration date when stored under the recommended conditions. Directions for Use of IntraVia * Containers

CAUTION:

Do not withdraw solution directly from the IntraViacontainer with a syringe.

*

Do not use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.

To Open: Tear foil overpouch (250mL Solution for Infusion) down side at slit and remove IntraVia * container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing inner bag firmly. If leaks are found, discard solution as sterility may be impaired. Do not use unless solution is clear and seal is intact. Do not add supplementary medication or withdraw solution directly from the bag with a syringe.

Preparation for administration

1. Suspend container from eyelet support.

2. Remove plastic protector from outlet port at bottom of container.

3. Attach administration set. Refer to complete directions accompanying set.

4. Any unused solution should be discarded.

*

Trademark of Baxter International Inc.

PHARMACEUTICAL INFORMATION

DRUG SUBSTANCE

Proper Name:

Tirofiban hydrochloride (USAN)

Chemical Name: N-(butylsulfonyl)-O[4-(4-piperidinyl)butyl]-L-tyrosine monohydrochloride monohydrate.

Structural Formula:

COOH C

HCl

. H 2O

HN CH 2CH 2CH 2CH 2O

H NHSO 2CH 2CH 2CH 2CH 3 Molecular Formula: C22H36N2O5S *HCl *H2O

Molecular Weight:

495.08

Physical Form:

Tirofiban hydrochloride is a white to off-white non-

hygroscopic free-flowing powder. It is very slightly soluble in water.

pH:

The pH of a 0.2% solution of tirofiban hydrochloride is approximately 2.9.

Melting Point:

Tirofiban hydrochloride melts with decomposition at

115degC (DSC curve).

COMPOSITION

AGGRASTAT(r) -- Concentrate for Infusion

Each mL of AGGRASTAT(r) -- Concentrate for Infusion contains 0.25 mg tirofiban as tirofiban hydrochloride. Inactive ingredients: 0.16 mg citric acid anhydrous, 2.7 mg sodium citrate dihydrate and 8 mg sodium chloride. The pH ranges from 5.5 to 6.5 and may have been adjusted with hydrochloric acid and/or sodium hydroxide.

AGGRASTAT(r) Solution for Infusion

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Each 250 mL of AGGRASTAT(r) & Solution for Infusion contains 12.5 mg tirofiban as tirofiban hydrochloride. Inactive ingredients: 8 mg citric acid anhydrous, 135 mg sodium citrate dihydrate and 2.25 g sodium chloride. The pH ranges from 5.5 to 6.5 and may have been adjusted with hydrochloric acid and/or sodium hydroxide. Each 500 mL of AGGRASTAT(r) Solution for Infusion contains 25 mg tirofiban as tirofiban hydrochloride. Inactive ingredients: 16 mg citric acid anhydrous, 270 mg sodium citrate dihydrate and 4.5 g sodium chloride. The pH ranges from 5.5 to 6.5 and may have been adjusted with hydrochloric acid and/or sodium hydroxide.

STABILITY AND STORAGE RECOMMENDATIONS

AGGRASTAT(r) -- Concentrate for Infusion

Store between 15-30degC. Do not freeze. Protect from light during storage. From a microbiological point of view, the diluted solution for infusion should be used immediately. If not used immediately, in-use storage conditions are the responsibility of the user and would normally not be longer than 24 hours at 2- 8degC, unless reconstitution has taken place in controlled and validated aseptic conditions. Single use vial; discard unused portion.

AGGRASTAT(r) Solution for Infusion

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Store between 15-25degC. Do not freeze Protect from light during storage.

AVAILABILITY OF DOSAGE FORMS

AGGRASTAT(r) & Concentrate for Infusion (concentrated solution for dilution) is supplied in 50 mL vials (0.25 mg/mL, tirofiban free base). AGGRASTAT(r) & Solution for Infusion (premixed, iso-osmotic solution) is supplied in 250 mL or 500 mL non-polyvinylchloride infusion bags (50 :g/mL, tirofiban free base).

TOXICOLOGY

Acute Toxicity

The approximate LD50 of tirofiban given as a single intravenous dose to mice or rats was >5 mg/kg. The maximum dose of 5 mg/kg (22 times the maximum recommended daily human dose) was limited by compound solubility and maximum acceptable dosing volume. The approximate LD50 of tirofiban given as a single oral dose to mice was >500 mg/kg. No mortality, physical signs, or compound-related effects on body weight were observed in either the intravenous or oral studies.

Chronic Toxicity

The toxic potential of tirofiban hydrochloride was evaluated for up to five weeks in a series of continuous infusion intravenous toxicity studies in rats and dogs. There were no findings that would preclude administration at the therapeutic dosage level for up to 108 hours.

Carcinogenesis

The carcinogenic potential of tirofiban hydrochloride has not been evaluated.

Mutagenesis

Tirofiban hydrochloride was negative in the 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. Tirofiban was tested in these in vitro assays at concentrations up to 3 mM, (approximately 20,000 times greater than the mean plasma level achieved in man at the recommended therapeutic dosage level). There was no induction of chromosomal aberrations in bone marrow cells of male mice after the administration of intravenous doses up to 5 mg/kg (22 times the maximum recommended daily human dose).

Reproduction

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. These dosages are approximately 22-fold higher than the maximum recommended daily dose in humans. Tirofiban crosses the placenta in rats and rabbits. Tirofiban is excreted in rat milk.

Development

Studies of developmental toxicity in rats and rabbits showed no evidence of maternal or fetal toxicity. In addition, a study of the potential developmental toxicity through sexual maturity of rats exposed in utero and during lactation showed no drug-related effects on mortality, growth, development, and sexual maturation of the F1 generation. In the developmental toxicity studies, dams were given tirofiban hydrochloride intravenously at doses up to 5 mg/kg/day.

SELECTED BIBLIOGRAPHY

1. Barrett JS, Murphy G, Peerlinck K, et al. Pharmacokinetics and pharmacodynamics of MK-383, a selective non-peptide platelet glycoprotein- IIb/IIIa receptor antagonist, in healthy men. Clin Pharmacol Ther 1994; 56(4):377-88.

2. Deckelbaum LI, Sax FL, Grossman W. Tirofiban, a nonpeptide inhibitor of the platelet glycoprotein IIb/IIIa receptor. In: Sasahara AA, Loscalzo J, eds. New therapeutic agents in thrombosis and thrombolysis. Marcel Dekker, Inc. 1997:355-65.

3. Kereiakes DJ, Kleiman NS, Ambrose J, et al. Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol 1996; 27(3):536-42.

4. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998; 338(21):1488-97.

5. Sutton J, Topol E, Rossen JD, et al. Inhibition of platelet aggregation with an infusion of MK-383 in stable coronary artery disease. Clin Res 1993; 41(2):118A.

6. Theroux P, White H, David D, et al. A heparin-controlled study of MK-383 in unstable angina [Abstract]. Circulation 1994; 90(4, Part 2):I231.

7. Bergquist PA, Hunke WA, Reed RA, Manas D, Forsyth RJ, Kenney RR, Cook J, Holahan M. Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration. J Clin Pharm Ther 1999; 24:125-32.