Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Concentrate, Intravenous:
Aggrastat: 3.75 mg/15 mL (15 mL)
Solution, Intravenous:
Aggrastat: 5 mg/100 mL in NaCl 0.9% (100 mL); 12.5 mg/250 mL in NaCl 0.9% (250 mL)
Pharmacology
Mechanism of Action
A reversible antagonist of fibrinogen binding to the glycoprotein (GP) IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, it inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained within 10 minutes after initiation. Platelet aggregation inhibition is reversible following cessation of the infusion.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss: 22 to 42 L
Metabolism
Negligible
Excretion
Urine (65%) and feces (25%) primarily as unchanged drug
Onset of Action
>90% inhibition of platelet aggregation (reversible after discontinuation) seen within 10 minutes
Half-Life Elimination
2 hours; Note: In ~90% of patients, ex vivo platelet aggregation returns to near baseline in 4 to 8 hours after discontinuation.
Protein Binding
65% (concentration dependent)
Use in Specific Populations
Special Populations: Renal Function Impairment
Plasma clearance is decreased by ~40% in patients with CrCl <60 mL/minute and more than 50% in patients with CrCl <30 mL/minute (including those requiring hemodialysis).
Use: Labeled Indications
Unstable angina/non-ST-elevation myocardial infarction: To decrease the rate of thrombotic cardiovascular events (combined end point of death, MI, or refractory ischemia/repeat cardiac procedure) in patients with non-ST-elevation acute coronary syndrome (unstable angina/non-ST-elevation myocardial infarction [UA/NSTEMI]).
Use: Off Label
To support PCI (administered at the time of PCI) for ST-elevation myocardial infarction (STEMI)ayes
Data from one double-blinded, randomized, controlled trial and one open-label, randomized, controlled trial supports the use of high-bolus dose tirofiban in the management of patients with STEMI undergoing primary PCI Valgimigli 2008, Van’t Hof 2008.
Based on the American College of Cardiology Foundation/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACCF/AHA/SCAI) guidelines for PCI and the ACCF/AHA guidelines for the management of STEMI, a glycoprotein IIb/IIIa inhibitor including tirofiban (high-bolus dose) given to support primary PCI is effective and recommended in the management of patients with STEMI undergoing primary PCI.
To support PCI (administered at the time of elective PCI) for stable ischemic heart disease (high risk features)byes
Data from a small, single-center, double-blind, placebo-controlled, randomized trial enrolling 202 patients with clinical or angiographic high-risk features (29% with stable angina) undergoing elective or urgent PCI supports the use of high-bolus dose tirofiban in the management of patients with stable ischemic heart disease and high risk features undergoing PCI Valgimigli 2004. Additional trials may be necessary to further define the role of tirofiban in this setting.
Based on the American College of Cardiology Foundation/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACCF/AHA/SCAI) guidelines for PCI, a glycoprotein IIb/IIIa inhibitor including tirofiban (high-bolus dose) given to support elective PCI is effective and recommended in the management of patients with stable ischemic heart disease and high risk features undergoing PCI.
Contraindications
Severe hypersensitivity reaction (ie, anaphylactic reaction) to tirofiban or any component of the formulation; history of thrombocytopenia following prior exposure to tirofiban; active internal bleeding or a history of bleeding diathesis, major surgical procedure, or severe physical trauma within the previous month
Canadian labeling: Additional contraindications (not in US labeling): History of thrombocytopenia following prior exposure to any other GPIIb/IIIa inhibitor; recent (within the previous 30 days) internal bleeding; history of intracranial hemorrhage or neoplasm, arteriovenous malformation, or aneurysm; history, symptom or findings suggestive of aortic dissection; 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 relevant trauma within the previous 6 weeks; malignant or severe uncontrolled hypertension (>180 mmHg/110 mmHg); current use with other GP IIb/IIIa inhibitors; acute pericarditis; cirrhosis or clinically significant liver disease; angina precipitated by obvious provoking factors (eg, arrhythmia, severe anemia, hyperthyroidism, hypotension); recent epidural procedure.
Dosage and Administration
Dosing: Adult
Unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI): IV: Loading dose: 25 mcg/kg administered over 5 minutes or less; Maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours
Percutaneous coronary intervention (PCI): IV: Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours (ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2004)
Stable ischemic heart disease (high-risk features) undergoing elective PCI (off-label use): Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute; was continued for up to 48 hours in the clinical trial (ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2004). Note: Reserve for patients who were not pretreated with clopidogrel or who are undergoing elective PCI with stent implantation with adequate clopidogrel pretreatment (ACCF/AHA/SCAI [Levine 2011]).
ST-elevation myocardial infarction (STEMI) undergoing primary PCI (off-label use): IV Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute in combination with heparin or bivalirudin in selected patients; was continued for 18-24 hours in clinical trials (ACCF/AHA [O’Gara 2013]; ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2008; Van’t Hof 2008)
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Do not dilute. Determine the volume needed to administer the loading dose using the 15 mL (concentration: 250 mcg/mL) premixed bolus vial or the 100 mL premixed vial (concentration: 50 mcg/mL) or 250 mL premixed bag (concentration: 50 mcg/mL). Determine the infusion rate of the maintenance infusion using the 100 mL premixed vial or 250 mL bag; do not use bags in series connections.
Administration
IV: Administer loading dose over 5 minutes or less, followed by a continuous infusion. Note: Clinical trials administered tirofiban loading dose over a period of 3 minutes (Valgimigli 2004; Valgimigli 2005; Valgimigli 2009).
Storage
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F); do not freeze. Protect from light during storage. Discard any unused portion.
Drug Interactions
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. Monitor therapy
Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy
Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Consider therapy modification
Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy
Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. Consider therapy modification
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Adverse Reactions
Bleeding is the major drug-related adverse effect. Patients received background treatment with aspirin and heparin. Adverse reactions reported are derived from both the high-dose bolus regimen and the dosing regimen used in studies that established the effectiveness of tirofiban. Frequency not always defined.
>10%: Hematologic & oncologic: Minor hemorrhage (TIMI criteria minor bleeding; 10.5% to 12%; transfusion required: 4% to 4.3%)
1% to 10%:
Cardiovascular: Coronary artery dissection (5%), bradycardia (4%), edema (2%), vasodepressor syncope (2%)
Central nervous system: Dizziness (3%), headache (>1%)
Dermatologic: Diaphoresis (2%)
Gastrointestinal: Nausea (>1%)
Genitourinary: Pelvic pain (6%)
Hematologic & oncologic: Major hemorrhage (TIMI criteria major bleeding: 1.4% to 2.2%; including hematoma [femoral]: 2% [Valgimigli 2005], intracranial bleeding, GI bleeding, retroperitoneal bleeding [Aydin 2003], GU bleeding, pulmonary alveolar hemorrhage [Guo 2012], spinal-epidural hematoma), thrombocytopenia: <90,000/mm3 (1.5% to 1.9%), <50,000/mm3 (0.3% to 0.5%)
Neuromuscular & skeletal: Leg pain (3%)
Miscellaneous: Fever (>1%)
<1%, postmarketing, and/or case reports: Anaphylaxis, hemopericardium, hypersensitivity, skin rash, urticaria
Warnings/Precautions
Concerns related to adverse effects:
- Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Fatal bleeding has been reported. Use with extreme caution in patients with platelet counts <150,000/mm3, patients with hemorrhagic retinopathy, previous history of GI disease, recent thrombolytic therapy and in chronic dialysis patients. Use caution with administration of other drugs affecting hemostasis. Minimize other procedures including arterial and venous punctures, IM injections, nasogastric tubes, etc.
- Thrombocytopenia: Profound thrombocytopenia has been reported with use of tirofiban. If during therapy platelet count decreases to <90,000/mm3, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue tirofiban and heparin if administered concurrently. Platelet counts should recover rapidly (within 1 to 5 days) after discontinuation. Previous exposure to a glycoprotein IIb/IIIa inhibitor may increase the risk of thrombocytopenia. Use is contraindicated in patients with a history of thrombocytopenia following exposure to tirofiban. Specific management guidelines for GP IIb/IIIa induced thrombocytopenia have been published (Huxtable 2006; Llevadot 2000).
Disease-related concerns:
- Renal impairment: Dosage reduction of the maintenance infusion rate is necessary in patients with CrCl ≤60 mL/minute.
Other warnings/precautions:
- Percutaneous coronary intervention: Sheath removal: Prior to pulling the sheath, ACT should be <180 seconds or aPTT <50 seconds (ACCF/AHA/SCAI [Levine, 2011]). Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.
- Surgery: Discontinue at least 2 to 4 hours prior to coronary artery bypass graft surgery (ACC/AHA [Amsterdam 2014]; ACCF/AHA [Hillis, 2011]).
Monitoring Parameters
Platelet count (baseline; 6 hours after initiation and daily thereafter during therapy). Monitor platelet counts more closely in patients who have had previous exposure to glycoprotein IIb/IIa antagonists. Persistent reductions of platelet counts <90,000/mm3 may require interruption or discontinuation of infusion; hemoglobin and hematocrit; signs of bleeding.
Standard post-PCI assessment if patient undergoes PCI (eg, monitoring vascular access site, monitoring for chest pain and signs of bleeding)
Pregnancy
Pregnancy Considerations
Information related to use in pregnancy is limited (Boztosun 2008; Hajj-Chahine 2010).
Patient Education
What is this drug used for?
- It is used to lower the chance of heart attack, the need for some heart treatments, or blockage of a stent after a stent is placed in the heart.
- It may be given to you for other reasons. Talk with the doctor.
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
