Tirofiban

Usage

• Tirofiban is prescribed for acute coronary syndrome (ACS), including unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI). It is used in conjunction with heparin and aspirin to decrease the rate of thrombotic cardiovascular events (death, myocardial infarction, or refractory ischemia/repeat cardiac procedure). It can be administered to patients managed medically or those undergoing percutaneous transluminal coronary angioplasty (PTCA) or atherectomy.
• Pharmacological Classification: Antiplatelet agent; Glycoprotein IIb/IIIa inhibitor.
• Mechanism of Action: Tirofiban reversibly inhibits the binding of fibrinogen to platelet glycoprotein (GP) IIb/IIIa receptors, preventing platelet aggregation.

Alternate Names

• International Nonproprietary Name (INN): Tirofiban
• Brand Name: Aggrastat

How It Works

• Pharmacodynamics: Tirofiban produces rapid and sustained inhibition of platelet aggregation by blocking the final common pathway of platelet aggregation. This reduces the formation of platelet-rich thrombi in coronary arteries.
• Pharmacokinetics:
  • Absorption: Administered intravenously, therefore 100% bioavailability.
  • Metabolism: Limited hepatic metabolism.
  • Elimination: Primarily renal excretion (approximately 65% as unchanged drug), with about 25% eliminated in feces.
  • Half-life: Approximately 2 hours.
  • Clearance: 213-314 mL/min (healthy subjects), 152-267 mL/min (patients with coronary artery disease).
• Mode of Action: Tirofiban selectively and competitively binds to the GP IIb/IIIa receptor on the platelet surface, blocking the binding of fibrinogen, von Willebrand factor, and other adhesive ligands. This inhibition prevents platelet cross-linking and aggregation.
• Receptor Binding: GP IIb/IIIa receptor antagonist.
• Elimination Pathways: Primarily renal excretion as unchanged drug.

Dosage

Standard Dosage

Adults:

• NSTE-ACS (Early Invasive Strategy <4 hours or Primary PCI): 25 mcg/kg intravenous bolus over 3 minutes, followed by a continuous infusion of 0.15 mcg/kg/min for 12-24 hours (up to 48 hours).
• NSTE-ACS (Early Invasive Strategy ≥4 hours to 48 hours) : 0.4 mcg/kg/min IV infusion for 30 minutes, then 0.1 mcg/kg/min continuous infusion for at least 48 hours (up to 108 hours maximum). Total treatment duration not to exceed 108 hours.

Children:

• Safety and efficacy not established in children under 18 years of age.

Special Cases:

• Elderly Patients: No dosage adjustment is necessary unless there is renal impairment.
• Patients with Renal Impairment (CrCl <30 mL/min): Reduce the maintenance dose by 50%. For the bolus regimen, administer 25 mcg/kg over 3 minutes and then infuse at 0.075 mcg/kg/min. For the loading dose regimen, the initial infusion rate is 0.2 mcg/kg/min for 30 minutes followed by 0.05 mcg/kg/min maintenance infusion.
• Patients with Hepatic Dysfunction: No dosage adjustment is recommended for mild to moderate hepatic impairment. Data for severe impairment are unavailable.
• Patients with Comorbid Conditions: Use caution in patients with recent bleeding, coagulopathy, platelet disorders, or history of thrombocytopenia.

Clinical Use Cases

• The dosage recommendations outlined above cover the clinical use cases, including ACS management with or without planned PCI and primary PCI for acute myocardial infarction. Dosages are optimized based on timing of angiography and whether the patient is managed with an early invasive strategy or not.

Dosage Adjustments

• See “Special Cases” above for renal impairment dosing adjustments.

Side Effects

Common Side Effects

• Bleeding (major or minor)
• Dizziness
• Slow heart rate
• Leg pain
• Pelvic pain
• Swelling
• Increased sweating

Rare but Serious Side Effects

• Severe allergic reactions (anaphylaxis)
• Severe thrombocytopenia
• Intracranial hemorrhage

Long-Term Effects

• Chronic bleeding complications may occur with prolonged use.

Adverse Drug Reactions (ADR)

• Profound thrombocytopenia, requiring urgent intervention.

Contraindications

• Hypersensitivity to tirofiban
• History of thrombocytopenia following prior tirofiban exposure
• Active internal bleeding or history of bleeding diathesis within 30 days
• History of intracranial hemorrhage, neoplasm, arteriovenous malformation, or aneurysm
• History of stroke within 30 days or any history of hemorrhagic stroke
• Major surgery or severe trauma within 1 month
• Suspected aortic dissection

Drug Interactions

• Anticoagulants (e.g., heparin, warfarin): Increased bleeding risk.
• Antiplatelet agents (e.g., aspirin, clopidogrel): Increased bleeding risk.
• Thrombolytics: Increased bleeding risk.
• CYP3A4 inhibitors or inducers: May affect tirofiban metabolism and clearance.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B (US FDA); B1 (Australia TGA). No adequate and well-controlled studies in pregnant women. Use only if clearly needed and the benefit outweighs the risk. Tirofiban crosses the placenta.
• Breastfeeding: Not known if tirofiban is excreted in human milk. Significant levels found in rat milk. A decision should be made to discontinue breastfeeding or discontinue the drug, considering the importance of the drug to the mother and the potential risk to the infant.

Drug Profile Summary

• Mechanism of Action: GP IIb/IIIa receptor antagonist, preventing platelet aggregation.
• Side Effects: Bleeding (major or minor), dizziness, bradycardia, allergic reactions.
• Contraindications: Active bleeding, history of thrombocytopenia with tirofiban, intracranial hemorrhage.
• Drug Interactions: Anticoagulants, antiplatelet agents, thrombolytics.
• Pregnancy & Breastfeeding: Category B; use only if clearly needed. Excretion in breast milk unknown.
• Dosage: Adults: Bolus 25 mcg/kg then 0.15 mcg/kg/min infusion; OR loading dose 0.4 mcg/kg/min then 0.1 mcg/kg/min infusion. Renal impairment: dose reduction needed.
• Monitoring Parameters: Platelet count, hemoglobin, hematocrit, signs of bleeding.

Popular Combinations

• Heparin
• Aspirin

Precautions

• General Precautions: Monitor for bleeding. Monitor platelet count, hemoglobin, hematocrit, and signs of bleeding.
• Specific Populations: See “Dosage - Special Cases”

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Tirofiban?

A: The dosage depends on the specific clinical situation (NSTE-ACS or primary PCI) and renal function. Please refer to the detailed dosage guidelines provided above.

Q2: What is the mechanism of action of Tirofiban?

A: Tirofiban blocks GP IIb/IIIa receptors on platelets, preventing fibrinogen binding and thus inhibiting platelet aggregation.

Q3: What are the major side effects of Tirofiban?

A: Bleeding is the most common and serious side effect. Other side effects may include dizziness, bradycardia, and allergic reactions.

Q4: When is Tirofiban contraindicated?

A: Tirofiban is contraindicated in patients with active bleeding, a history of thrombocytopenia after prior tirofiban exposure, or a history of intracranial hemorrhage.

Q5: How does renal impairment affect Tirofiban dosage?

A: Patients with severe renal impairment (CrCl <30 mL/min) require a 50% reduction in the maintenance infusion dose.

Q6: Can Tirofiban be used during pregnancy?

A: Tirofiban is a Pregnancy Category B drug. It should be used during pregnancy only if clearly needed and the potential benefit outweighs the risk.

Q7: What drugs interact with Tirofiban?

A: Tirofiban interacts with anticoagulants, antiplatelet agents, and thrombolytics, increasing the risk of bleeding. It also interacts with drugs metabolized by CYP3A4.

Q8: How should Tirofiban be administered?

A: Tirofiban is administered intravenously, either as a bolus followed by continuous infusion or as a loading dose followed by continuous infusion.

Q9: What are the monitoring parameters for patients on Tirofiban?

A: Platelet counts, hemoglobin, hematocrit, signs and symptoms of bleeding, and other coagulation parameters should be monitored regularly.

Q10: Should Tirofiban be used in children?

A: The safety and efficacy of Tirofiban in children have not been established.