Tirofiban

Class: Platelet-Aggregation Inhibitors
ATC Class: B01AC17
Chemical Name: N-(butylsulfonyl)-4-[4-(4-piperidyl)butoxy]-l-phenylalanine monohydrochloride monohydrate
Molecular Formula: C₂₂H₃₆N₂O₅S
CAS Number: 144494-65-5
Brands: Aggrastat

Introduction

Platelet-aggregation inhibitor;^{1 15 22} a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor.^b

Uses for Tirofiban

Unstable Angina and Non-ST-Segment Elevation MI

Adjunct to anticoagulant therapy (e.g., unfractionated heparin, low molecular weight heparin), aspirin, and/or clopidogrel to reduce risk of acute cardiac ischemic events (death and/or MI) in patients with non-ST-segment elevation acute coronary syndrome (i.e., unstable angina or non-ST-segment elevation MI), including those who are to receive medical management or to undergo PCI.^{1 5 6 21 91 100 103 104 107 116}

Adjunctive therapy with a GP IIb/IIIa-receptor inhibitor can reduce the incidence of cardiac ischemic events, including subsequent MI and death, in patients with non-ST-segment-elevation acute coronary syndromes.^{5 6 11 35 36 42 46 51 71 72 73 80 83 84 85 91 103 111}

The American College of Chest Physicians (ACCP) recommends initial (at presentation or diagnosis, “upstream”) treatment with certain GP IIb/IIIa-receptor inhibitors (i.e., tirofiban or eptifibatide) or clopidogrel in conjunction with an anticoagulant and aspirin in patients with non-ST-segment-elevation acute coronary syndromes who have at least a moderate risk for adverse cardiac ischemic events and who will undergo an early invasive procedure.¹¹¹ Alternatively, ACCP suggests use of eptifibatide or tirofiban in addition to clopidogrel and in conjunction with anticoagulation and aspirin therapy as initial treatment for patients at moderate or greater risk who will undergo an early or delayed invasive procedure.^{107 111}

ACCP recommends bivalirudin with provisional use of a GP IIb/IIIa-receptor inhibitor or unfractionated heparin and a GP IIb/IIIa-receptor inhibitor in patients who are at a low to moderate risk for an ischemic event who are undergoing PCI.¹¹¹ In patients undergoing elective PCI with stent placement, ACC and AHA consider the use of GP IIb/IIIa-receptor inhibitors (abciximab, eptifibatide, tirofiban) to be reasonable.¹⁰³

ACCP, ACC, and AHA currently recommend therapy with a GP IIb/IIIa-receptor inhibitor in all patients undergoing PCI, particularly in patients who have refractory non-ST-segment-elevation acute coronary syndromes or other high-risk features.^{103 104 109 111} ACC/AHA/SCAI recommend a GP IIb/IIIa-receptor inhibitor (abciximab, eptifibatide, tirofiban) without clopidogrel prior to diagnostic angiogram or just before PCI;^{103 109} however, ACCP recommends a GPIIb/IIIa-receptor inhibitor with clopidogrel in such patients.¹¹¹

ACCP does not recommend use of tirofiban as an alternative to abciximab in patients undergoing PCI in whom a GP IIb/IIIa-receptor inhibitor has not been initiated previously (“upstream”).^{106 111}

Tirofiban and eptifibatide not recommended by AHA in women with non-ST-segment elevation acute coronary syndromes who are at lower risk for adverse events and are managed with conservative strategy, because of little demonstrated benefit and possible detrimental effects.¹⁰⁹

Tirofiban Dosage and Administration

General

• 
  

  Administer as soon as possible following diagnosis.^{21 91}

  
  


• 
  

  Discontinue at least 4–6 hours prior to CABG.^{21 91}

  
  

Adjunctive Antithrombotic Therapy

• 
  

  In clinical trials, almost all patients receiving tirofiban also received concomitant aspirin and/or unfractionated heparin.^{1 5 6 11 14} Tirofiban and heparin may be administered through the same IV line.¹

  
  

  Used in conjunction with aspirin and unfractionated heparin in clinical studies.^{1 5 6 11 14}

  
  


• 
  

  Aspirin: In clinical studies, patients received 300–325 mg daily for at least 48 hours after randomization or within 12 hours prior to PCI, unless the drug was contraindicated; some patients received aspirin indefinitely.^{1 5 6 11 14} ACCP recommends initial and maintenance aspirin dosages of 162–325 mg and 75–100 mg daily, respectively.^{111 114} ACC/AHA/SCAI recommend 300–325 mg ≥2 hours, preferably 24 hours, prior to PCI in patients not already receiving maintenance therapy with aspirin.^{103 112} In patients already receiving maintenance therapy with aspirin, give 75–325 mg before the procedure.^{103 112}

  
  


• 
  

  Clopidogrel in patients managed with conservative medical therapy or early or delayed invasive procedures: Initially, a loading dose of 300 mg is recommended;¹¹¹ initiate as soon as possible during hospitalization and continue at a maintenance dosage of 75 mg once daily.^{104 114} Some clinicians recommend continuing therapy with clopidogrel and aspirin for ≥1 month but ideally up to 1 year in patients receiving medical management only.^{104 114 116} ACCP recommends a maintenance clopidogrel dosage of 75 mg once daily for 12 months in conjunction with aspirin, and then continuance of aspirin indefinitely for patients managed with a conservative medical approach.¹¹⁴

  
  


• 
  

  Heparin during medical management: In clinical studies, patients received an IV loading dose of 5000 units followed by continuous IV infusion of 1000 units/hour.^{1 5 6} (See Laboratory Monitoring under Cautions.)

  
  


• 
  

  Heparin prior to PCI: In clinical studies, patients undergoing PCI after at least 48 hours of medical management received an IV loading dose of 5000–7500 units followed by continuous IV infusion of 1000 units/hour titrated to an aPTT approximately 2 times the control value with additional IV injections of heparin as needed. (See Laboratory Monitoring under Cautions.)^{1 6}

  
  


• 
  

  Heparin prior to urgent PCI: In a clinical study, patients at high risk for abrupt closure of the affected coronary artery who underwent urgent or emergency PCI received an IV loading dose of 10,000 units (body weight ≥70 kg) or 150 units/kg (body weight <70 kg).^{1 11 37 44} In clinical studies, additional injections during PCI were administered to maintain target activated clotting time (ACT) between 300–400 seconds.^{1 11 37 44} ACCP, ACC, AHA, and SCAI^{53 103} suggest use of lower dosages of concomitant IV heparin (50–70 units/kg) prior to PCI and targeted to an ACT of ≥200 seconds.^{1 18 35 44 53 71 74 77 80 81 95 96 102 106 110 111} Additional injections of heparin sodium may be given during PCI to maintain an ACT of 200–300 seconds.^{103 112} (See Laboratory Monitoring under Cautions.)

  
  


• 
  

  Postprocedural use of heparin not recommended.^{6 11 42 52 53 102 103 106}

  
  


• 
  

  Fondaparinux: In patients managed initially with fondaparinux, a GP IIb/IIIa-receptor inhibitor, and a delayed invasive strategy, ACCP recommends additional IV injections of fondaparinux sodium† (2.5 mg) and heparin sodium (e.g., 50–60 units/kg) be given at the time of the procedure.^{111 112}

  
  

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using either diluted injection concentrate or premixed injection in plastic (IntraVia™) containers.^{1 1}

Discard unused portion.¹

The plastic container of the premixed injection may be somewhat opaque because of moisture absorption during sterilization; this opacity will diminish gradually.¹

Do not introduce additives into the injection container.¹

Do not use the plastic IV container in series connections with other plastic containers; such use may result in air embolism.¹

Dilution

Tirofiban hydrochloride injection concentrate for IV infusion must be diluted to 50 mcg/mL (the same concentration as the premixed injection) before administration.¹

Prepare injection concentrate for infusion by withdrawing and discarding 50 or 100 mL of solution from a 250- or 500-mL bag, respectively, of 0.9% sodium chloride or 5% dextrose injection and replacing this volume with an equivalent volume (i.e., 50 or 100 mL, respectively) of tirofiban hydrochloride injection to achieve a final concentration of 50 mcg/mL.^{1 21}

Alternatively, a vial labeled as containing 5 mg of tirofiban may be added to a 100 mL bag of 0.9% sodium chloride injection or 5% dextrose injection.¹

Mix solutions well prior to infusion.¹

Rate of Administration

Administer as a continuous infusion.^{1 20 21 91}

Dosage

Available as tirofiban hydrochloride; dosage expressed in terms of tirofiban.¹

Adults

Unstable Angina and Non-ST-Segment Elevation MI

IV

Patients receiving medical therapy: IV loading dose of 0.4 mcg/kg per minute for 30 minutes given as soon as possible after diagnosis, followed by continuous IV infusion of 0.1 mcg/kg per minute for at least 24–48 hours.^{21 91}

Patients who undergo PCI: IV loading dose of 0.4 mcg/kg per minute for 30 minutes followed by continuous IV infusion of 0.1 mcg/kg per minute given during angiography and for 12–24 hours after angioplasty or atherectomy.^{1 20 21 91}

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.^{1 20}

Renal Impairment

In patients with severe renal impairment (i.e., Cl_cr≤ 30 mL/minute), decrease the usual loading and maintenance rate of infusion by 50%.¹

Geriatric Patients

Dosage adjustment not required.¹

Cautions for Tirofiban

Contraindications

• 
  

  Active internal bleeding or history of bleeding diathesis ^{1 5 6 14 20 21 91} within previous 30 days.^{1 20 21 91}

  
  


• 
  

  History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm.^{1 52}

  
  


• 
  

  History of thrombocytopenia following prior exposure to tirofiban.^{1 5 6 11 20 52}

  
  


• 
  

  History of stroke within 30 days or any history of hemorrhagic stroke.^{1 5 6 11 14 20 52}

  
  


• 
  

  Recent (within 30 days) major surgery or severe physical trauma.^{1 5 20 52}

  
  


• 
  

  History, symptoms, or findings suggestive of aortic dissection.^{1 20}

  
  


• 
  

  Severe uncontrolled hypertension (SBP >180 or DBP >110 mm Hg).^{1 5 20}

  
  


• 
  

  Concomitant therapy with another parenteral GP IIb/IIIa-receptor inhibitor.^{1 20}

  
  


• 
  

  Acute pericarditis.^{1 20}

  
  


• 
  

  Known hypersensitivity to tirofiban or any ingredient in the formulation.^{1 20}

  
  

Warnings/Precautions

Warnings

Hematologic Effects

Risk of major bleeding (e.g., intracranial hemorrhage, GU or GI bleeding, bleeding at arterial access site) and minor bleeding (e.g., spontaneous gross hematuria, spontaneous hematemesis); may require blood or platelet transfusions.^{1 5 6 11 20 21 91} (See Bleeding Precautions and also see Laboratory Monitoring under Cautions.)

Pulmonary alveolar hemorrhage, spinal-epidural hematoma, retroperitoneal bleeding, and hemopericardium reported rarely.¹

Fatal hemorrhage reported rarely.¹

Use with caution in patients with platelet count <150,000/mm³, anemia (hemoglobin <10–12 g/dL), hemorrhagic retinopathy, and those requiring chronic hemodialysis.^{1 20 91}

Use with caution in patients receiving other drugs that affect hemostasis (e.g., thrombolytic agents, oral anticoagulants, NSAIAs, dipyridamole, ticlopidine, and clopidogrel).^{1 20 21 91} (See Specific Drugs under Interactions.)

If bleeding cannot be controlled by pressure, discontinue tirofiban and concomitant heparin.^{1 20}

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and other severe allergic reactions reported on the first day of infusion, during initial treatment, and during readministration of the drug.^{1 21}

Severe allergic reactions sometimes associated with severe thrombocytopenia (platelet counts <10,000/mm³).¹

General Precautions

Bleeding Precautions

To reduce risk of bleeding, adhere to strict anticoagulation guidelines; use a short course of low-dose, weight-adjusted heparin; avoid vascular and other trauma; carefully manage vascular (e.g., femoral artery) access site; and monitor all potential bleeding sites during and following treatment.^{1 5 6 11 21 91}

In patients undergoing PCI, use caution in the placement, maintenance, and removal of vascular access sheath; avoid femoral vein sheath placement.^{1 18 35 37 42 46 52} When inserting sheath, puncture only anterior wall of femoral artery; avoid Seldinger (through and through) technique.^{1 18 20 52 77 81} Observe appropriate precautions while sheath is in place (e.g., complete bed rest, elevation of head ≤30°, restrain limb in which sheath is inserted, frequent monitoring of vascular access site and distal pulse in the involved limb).^{1 18 19 20 52} Following PCI, consider early sheath removal (during tirofiban IV infusion).¹ Prior to removal of sheath, discontinue heparin for 3–4 hours and allow aPTT to return to <45 seconds or ACT to <180 seconds.^{1 11 14 20 30 41 52 53 70} Discontinue tirofiban and heparin and achieve hemostasis (by applying pressure to femoral artery for at least 20–30 minutes after sheath removal^{18 19} ) at least 4 hours before hospital discharge.^{1 20} Measure and monitor hematomas for enlargement.¹⁸

To avoid vascular and other trauma, minimize needle punctures (e.g., arterial, IM, IV, lumbar, sub-Q, intradermal), cutdown sites, and use of nasotracheal intubation, nasogastric tubes, urinary catheters,^{1 18 20} and automatic BP cuffs¹⁸ during and following treatment;^{1 18} avoid establishment of IV access at noncompressible sites (e.g., subclavian or jugular veins);^{1 18} consider using an indwelling venipuncture device (e.g., heparin lock) for drawing blood; document and monitor vascular puncture sites; and remove dressings gently and carefully.¹⁸

Thrombocytopenia

Thrombocytopenia reported.^{1 5 32 37 43 44 45 50 52} Severe thrombocytopenia (platelet count <20,000/mm³) reported less frequently than with abciximab.^{18 30 32 35 37 44 50 53}

Determine platelet counts prior to treatment and periodically (e.g., within the first 6 hours of the loading infusion, and daily thereafter) during concomitant tirofiban and heparin therapy.^{1 11 20 43 44} Consider possibility of pseudothrombocytopenia or heparin-induced thrombocytopenia in patients receiving concomitant heparin therapy.^{1 20 35 37 52} (See Thrombocytopenia under Cautions.)

If true thrombocytopenia is verified, discontinue tirofiban and initiate appropriate treatment and monitoring.¹ Thrombocytopenia usually reversible following discontinuance of GP IIb/IIIa-receptor inhibitors and anticoagulant (heparin) therapy; consider platelet transfusions for the management of severe thrombocytopenia.^{35 37 43 52}

Use with caution in patients with platelet count <150,000/mm³;^{1 20} contraindicated in patients with a history of thrombocytopenia following prior exposure to tirofiban.^{1 5 6 11 20 52}

Laboratory Monitoring

Prior to administration, within the first 6 hours of the loading infusion and at least daily thereafter, obtain hematocrit and hemoglobin,^{1 11 20 35 43 44} and platelet counts.^{1 11 20 35 43 44}

Closely monitor ACT or aPTT.^{1 30 52 70} Monitor aPTT 6 hours after the start of the heparin infusion and maintain at 50–70 seconds or approximately 2 times the control value unless PCI is to be performed.^{1 6 30} In patients undergoing PCI, measure the ACT.^{21 52 70 103} In patients undergoing PCI in clinical studies, ACT was maintained between 300–400 seconds during PCI;^{1 11 37 44} ACCP suggests targeting ACT between 200–250 seconds to reduce risk of major bleeding.^{1 18 35 44 53 71 74 77 80 81 95 96 102} Monitor aPTT or ACT prior to arterial sheath removal; do not remove sheath unless aPTT <45 seconds or ACT <180 seconds.^{1 30 41 53 70 102}

Determine platelet counts prior to administration, within the first 6 hours of the loading infusion and at least daily thereafter.^{1 11 20 43 44} Perform additional platelet counts if a patient experiences a reduction in platelet count to <90,000/mm³ to exclude the possibility of pseudothrombocytopenia.^{1 18 90}

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in rats;¹ not known whether distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.^{1 20}

Geriatric Use

No substantial differences in efficacy relative to younger adults.¹ However, increased incidence of bleeding complications and non-bleeding adverse events in some studies.^{1 20}

Women

Increased incidence of minor bleeding complications and non-bleeding adverse events in some studies.^{1 103 109}

Hepatic Impairment

Clearance not affected in patients with mild to moderate hepatic impairment;^{1 20} information on plasma clearance limited in patients with severe hepatic impairment since these patients were excluded from participation in clinical studies.²¹

Renal Impairment

Substantially decreased clearance (>50%) in patients with severe renal impairment (i.e., Cl_cr ≤30 mL/minute), including patients requiring hemodialysis;¹ reduced dosage recommended in such patients.^{1 20} (See Renal Impairment under Dosage and Administration.)

Use with caution in patients requiring chronic hemodialysis.^{1 20 91}

Common Adverse Effects

Bleeding,¹ pelvic pain,¹ coronary artery dissection,¹ bradycardia,¹ leg pain,¹ dizziness,¹ edema/swelling, ¹ vasovagal reaction,¹ sweating.¹

Interactions for Tirofiban

Specific Drugs

Drug	Interaction	Comments
Anticoagulants, oral	Potential increased risk of bleeding1	Use with caution1 20 21 91
Clopidogrel	Potential increased risk of bleeding1 4 22	Use with caution1 20 21 91
Dextran	Increased risk of bleeding1	Some clinicians recommend against concomitant use91
Dipyridamole	Potential increased risk of bleeding1	Use with caution1 20 21 91
GP IIb/IIIa-receptor inhibitors (abciximab, eptifibatide)	Possible additive pharmacologic effects1 4	Concomitant use contraindicated1
Heparin	Increased risk of bleeding; 1 5 6 11 14 possible additive effects on ACT56 100	Monitor aPTT or ACT during therapy;1 5 6 11 37 44 consider dosage adjustment of heparin56 100
Levothyroxine	Possible increased tirofiban clearance 1	Clinical importance not known1
NSAIAs	Potential increased risk of bleeding1	Use with caution1 20 21 91
Omeprazole	Possible increased tirofiban clearance 1	Clinical importance not known1
Thrombolytics	Increased risk of bleeding1	Use concomitantly with caution; no concomitant use studies to date20 21 91
Ticlopidine	Potential increased risk of bleeding1 4 22	Use with caution1 20 21 91

Tirofiban Pharmacokinetics

Absorption

Onset

Rapid onset;^{11 14 20} 90% inhibition of platelet aggregation occurs by the end of the IV loading infusion administration.^{1 20 21}

Duration

Short duration of action;^{11 14 20} platelet aggregation persists during maintenance infusion.^{1 20 21} Platelet function generally recovers within 4–8 hours following discontinuance of infusion.^{1 20}

Distribution

Extent

Distributed into milk in rats and crosses the placenta in pregnant rats and rabbits.^{1 20} Not known whether tirofiban crosses the placenta or is distributed into milk in humans.^{1 20}

Plasma Protein Binding

Approximately 65%.^{1 4 20}

Elimination

Metabolism

Metabolism appears limited.^{1 20}

Elimination Route

Excreted in urine (65%) and in feces (25%) mainly as unchanged drug.^{1 20}

Half-life

Approximately 1.2–2 hours.^{1 3 4 15 20 22 91}

Special Populations

Plasma clearance may decrease substantially (>50%) in patients with severe renal impairment (i.e., Cl_cr ≤30 mL/minute and those requiring hemodialysis) ¹ (See Renal Impairment under Dosage and Administration.)

Removed by hemodialysis.^{1 20}

Plasma clearance decreased approximately 19–26% in geriatric patients.²⁰

Stability

Storage

Parenteral

For Injection, Concentrate, for IV Infusion

25°C (may be exposed to 15–30°C).^{1 20} Do not freeze; protect from light.^{1 20}

Contains no preservative; discard unused solution.¹

Injection, for IV Infusion

25°C (may be exposed to 15–30°C).¹ Do not freeze; protect from light.¹

Contains no preservative; discard unused solution.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 5% in sodium chloride 0.45%
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility

Y-Site Compatibility1HID

Compatible
Amiodarone HCl
Atropine sulfate
Bivalirudin
Dobutamine HCl
Dopamine HCl
Epinephrine HCl
Famotidine HCl
Furosemide
Heparin sodium
Lidocaine HCl
Midazolam HCl
Morphine sulfate
Nitroglycerin
Potassium chloride
Propranolol HCl
Incompatible1 HID
Diazepam

ActionsActions

• 
  

  Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other adhesive ligands to GP IIb/IIIa receptors).^{1 11 16 17 22 24 43 45}

  
  


• 
  

  Modest effect on hemostatic indices (e.g., bleeding times);^{1 2} normal hemostasis restored more rapidly than with abciximab.^{8 31 32 35 74 91}

  
  


• 
  

  Usually does not affect aPTT when administered as monotherapy.^{5 6}

  
  

Advice to Patients

• 
  

  Risk of serious bleeding or hemorrhage.¹

  
  


• 
  

  Importance of close laboratory monitoring.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Tirofiban Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, concentrate, for IV infusion	250 mcg (of tirofiban) per mL (5 and 12.5 mg)	Aggrastat	Medicure

Tirofiban Hydrochloride in Sodium Chloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IV infusion	50 mcg (of tirofiban) per mL (5 and 12.5 mg) in 0.9% Sodium Chloride	Aggrastat Premixed in Iso-osmotic Sodium Chloride Injection (in IntraVia flexible container)	Medicure

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Medicure Pharma. Aggrastat (tirofiban hydrochloride) injection premixed and injection prescribing information. Somerset, NJ; 2007 Nov.

2. Anon. Tirofiban hydrochloride. Drugs Future. 1995; 20:897-901.

3. Umemura K, Kondo K, Ikeda Y et al. Enhancement by ticlopidine of the inhibitory effect on in vitro platelet aggregation of the glycoprotein IIb/IIIa inhibitor tirofiban. Thromb Haemost. 1997; 78: 1381-4.

4. Barrett JS, Murphy G, Peerlinck K et al. Pharmacokinetics andpharmacodynamics of MK-383, a selective non-peptide platelet glycoprotein-IIb/IIIa receptor antagonist, in healthy men. Clin Pharmacol Ther. 1994; 56:377-88. [IDIS 338167] [PubMed 7955799]

5. The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998; 338:1498-1505. [IDIS 409093] [PubMed 9599104]

6. The 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; 338:1488-97. [IDIS 405092] [PubMed 9599103]

7. Agency for Health Care Policy and Research. Diagnosing and managing unstable angina. 1994. (AHCPR publication no. 94-0603)

8. Chesebro JH, Badimon JJ. Platelet glycoprotein IIb/IIIa receptor blockade in unstable coronary disease. N Engl J Med. 1998; 338:1539-41. [IDIS 405098] [PubMed 9593795]

9. Théroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation. 1997; 97:1195-206.

10. Braunwald E, Maseri A, Armstrong PW et al. Rationale and clinical evidence for the use of GP IIb/IIIa inhibitors in acute coronary syndromes. Eur Heart J. 1998; 19(Suppl. D):D22-30. [PubMed 9597519]

11. The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation. 1997; 96:1445-53. [IDIS 393118] [PubMed 9315530]

12. Tcheng JE. Platelet glycoprotein IIb/IIIa integrin blockade: recent clinical trials in interventional cardiology. Thromb Haemost. 1997; 78:205-9. [IDIS 392079] [PubMed 9198154]

13. Hahn SS, Chae C, Giugliano R et al. Troponin I levels in unstable angina/non-Q wave myocardial infarction patients treated with tirofiban, a glycoprotein IIb/IIIa antagonist. J Am Coll Cardiol. 1998; 31(Suppl. A):229A.

14. 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; 27:536-42. [IDIS 364310] [PubMed 8606262]

15. Peerlinck, De Lepeleire I, Goldberg M et al. MK-383 (L-700,462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man. Circulation. 1993; 88:1512-7. [IDIS 321320] [PubMed 8403299]

16. Hartman GD, Egbertson MS, Halczenko W et al. Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J Med Chem. 1992; 35:4640-2. [PubMed 1469694]

17. Egbertson MS, Chang CTC, Duggan ME et al. Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for arg-gly-asp. J Med Chem. 1994; 37:2537-51. [PubMed 8057299]

18. Eli Lilly and Company. ReoPro (abciximab) injection for intravenous use prescribing information. Indianapolis, IN; 1997 Ju