Tirofiban (Aggrastat) reversibly inhibits the binding of fibrinogen to the major platelets surface receptor GP-IIb/IIIa.

It inhibits platelets aggregation and is used in the following situations:

• Unstable angina/non-ST-elevation myocardial infarction:

  • It is used to lessen the rate of thrombotic cardiovascular events (combined endpoint of death, MI, or refractory ischemia/repeat cardiac procedure) in patients with the non-ST-elevation acute coronary syndrome (unstable angina/non-ST-elevation myocardial infarction.

• Off Label Usage of Tirofiban in Adults:

  • It is used to support PCI (given at the time of PCI) for ST-elevation myocardial infarction (STEMI);

  • It is used to support PCI (given at the time of elective PCI) for stable ischemic heart disease (high-risk features)

Tirofiban Dose in Adults

Tirofiban dosage in the treatment of Unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI):

• IV:
  • The loading dose is given as 25 mcg/kg administered over 5 minutes or less
  • Maintenance infusion is  0.15 mcg/kg/minute continued for up to 18 hours

Dosage in the treatment of Percutaneous coronary intervention (PCI):

• IV:
  • The loading dose is 25 mcg/kg administered over 5 minutes or less at the time of PCI
  • Maintenance infusion is given 0.15 mcg/kg/minute continued for up to 18 hours

Off label dosage in the treatment of stable ischemic heart disease (high-risk features) undergoing elective PCI:

• Loading dose:
  • 25 mcg/kg given over 5 minutes or less at the time of PCI;
  • Maintenance infusion is given as 0.15 mcg/kg/minute
  • It is reserved for patients who were not pretreated with clopidogrel or who are undergoing elective PCI with stent implantation with adequate clopidogrel pretreatment.

Off label dosage in the treatment of ST-elevation myocardial infarction (STEMI) undergoing primary PCI:

• IV Loading dose:
  • 25 mcg/kg is given over 5 minutes or less at the time of PCI;
  • Maintenance infusion is given as 0.15 mcg/kg/minute in combination with heparin or bivalirudin in selected patients

Tirofiban Dose in Childrens

Not recommmended.

Tirofiban (Aggrastat) pregnancy Risk Factor: B

• Pregnancy has not been associated with any adverse events.

Use of Tirofiban while breastfeeding

• It is unknown if tirofiban can be found in breast milk.
• According to the manufacturer breastfeeding during therapy should be considered in order to minimize infant exposure and to maximize the benefits for the mother 

Tirofiban (aggrastat) dose in Renal disease:

• Renal function may be evaluated using the Cockcroft-Gault formula using actual body weight.

• CrCl >60 mL/minute:

  • No dosage reduction required.

• CrCl ≤60 mL/minute:

  • IV Loading dose is 25 mcg/kg administered over ≤5 minutes
  • Maintenance infusion is 0.075 mcg/kg/minute continued for up to 18 hours.

• Hemodialysis:

  • It is dialyzable

Tirofiban Dose in Liver Disease:

Tirofiban (aggrastat) should be avoided in severe liver disease. In mild to moderate liver disease, it should be used with caution.

• Bleeding is the major drug-related side effect.
• Patients also received background treatment with aspirin and heparin.
• Adverse reactions seen 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.

Common Side Effects of Tirofiban (Aggrastat) Include:

• Hematologic & oncologic:

  • Minor hemorrhage

Less Common Side Effects of Tirofiban (Aggrastat) Include:

• Cardiovascular:

  • Coronary Artery Dissection
  • Bradycardia
  • Edema
  • Vasodepressor Syncope

• Central Nervous System:

  • Dizziness
  • Headache

• Dermatologic:

  • Diaphoresis

• Gastrointestinal:

  • Nausea

• Genitourinary:

  • Pelvic Pain

• Hematologic & Oncologic:

  • Major Hemorrhage
  • Thrombocytopenia: <90,000/Mm
  • <50,000/Mm

• Neuromuscular & Skeletal:

  • Leg Pain

• Miscellaneous:

  • Fever

Contraindication to Tirofiban (Aggrastat) Include:

• Anaphylactic reactions (i.e. severe hypersensitivity) to tirofiban and any component of the formulation
• Tirofiban exposure in the past has caused thrombocytopenia;
• Active internal bleeding or history of bleeding diathesis
• Major surgery or severe trauma in the last month
• History of thrombocytopenia after prior exposure to any other GPIIb/IIIa inhibitor
• Recent (within the last 1 month) internal bleeding
• History of intracranial hemorhage or Neoplasm
• Aneurysm or AV malformation
• History, symptoms or findings that suggest aortic dissection
• History of thrombocytopenia, platelet disorder, or coagulopathy previously known;
• Stroke within one month of hospitalization, or history of hemorhagic stroke
• A major surgery or trauma that occurred within the past 6 weeks.
• Malignant hypertension or severe uncontrolled hypertension (>180mmHg/110mmHg);
• Current use with other GP IIb/IIIa inhibitors
• acute pericarditis;
• Cirrhosis and clinically significant liver disease
• Angina can be caused by obvious factors such as arrhythmias, severe anemias, hyperthyroidism and hypotension.
• recent epidural procedure.

Warnings and precaution

• Bleeding

  • Bleeding is the most common side effect. This includes retroperitoneal, lung, spontaneous GI, and GU bleeding.
  • Be on the lookout for bleeding, particularly at the site of cardiac catheterization.
  • There have been cases of fatal bleeding.
  • Patients with low platelet counts (150,000/mm3), patients with hemorhagic retinopathy, patients who have had recent thrombolytic therapy, and patients on chronic dialysis should be cautious.
  • Be careful when you are taking any other medications that affect hemostasis.
  • Other procedures, such as IM injections and arterial and venous punctures should be minimized.

• Thrombocytopenia:

  • Tirofiban has been associated with severe thrombocytopenia.
  • Monitor platelet counts if they fall below 90,000.
  • Stop taking tirofiban or heparin concurrently if thrombocytopenia is confirmed.
  • After stopping, platelet counts should quickly recover (within 1-5 days).
  • The risk of developing thrombocytopenia can be increased by previous exposure to a glycoprotein IIb/IIIa inhibitor.

Tirofiban: Drug Interaction

Monitor:

• Platelet count (baseline; 6 hours after starting and daily thereafter during therapy).
• Monitor platelet counts more closely in patients who have had previous exposure to glycoprotein IIb/IIa antagonists.
• If persistent reductions of platelet counts <90,000/mm happen then it may require interruption or discontinuation of infusion;
• hemoglobin and hematocrit;
• signs of bleeding.
• Standard post-PCI assessment if the patient has PCI (eg, monitoring vascular access site, monitoring for chest pain and signs of bleeding)

How to administer Tirofiban (Aggrastat)?

• Give a loading dose over 5 minutes or less intravenously,
• It is followed by a continuous infusion.

Mechanism of action of Tirofiban (Aggrastat):

• It acts as a reversible antagonist to fibrinogen binding at the glycoprotein IIb/IIIa receptor. This receptor is the main platelet surface receptor that plays a role in platelet aggregation.
• When given intravenously, it inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner.
• If the prescribed regimen is followed, you will achieve more than 90% inhibition within 10 minutes of initiating.
• After stopping the infusion, platelet aggregation inhibition may be reversed.

Onset: more than 90% inhibition of platelet aggregation (reversible after discontinuation) seen within 10 minutes

Distribution: V : 22 - 42 L

Protein Binding: 65% (concentration-dependent)

Metabolism: It is Negligible

Half-life elimination: 2 hours

Excretion: By urine (65%) and feces (25%) primarily as unchanged drug

International Brands of Tirofiban:

• Aggrastat
• Agrastat
• Eupifiban
• Sunnycardio
• Tiroprest

Tirofiban Brands in Pakistan: