Tirofiban

Tirofiban is an antiplatelet agent belonging to Glycoprotein IIb/IIIa Inhibitor.

Tirofiban is a platelet aggregation inhibitor used to prevent thrombotic events in non-ST elevated acute coronary syndrome.

The volume of distribution of Tirofiban is about 22 to 42 L. The Plasma protein binding is approximately 65%. It is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban. Half-life is about 2 hours.

Tirofiban shows common side effects like Abdominal or stomach pain or swelling, Pain in the arm, back, or jaw, black or tarry stools, blood in the eyes, blood in the urine, bruising or purple areas on the skin, chest pain or discomfort, chest tightness or heaviness, coughing up blood, decreased alertness, fast or irregular heartbeat, headache, joint pain or swelling, nausea, nosebleeds.

Tirofiban is available in the form of an Injectable Solution.

Tirofiban is available in India, the US, Zealand, South Africa, Canada, China, and Russia.

Tirofiban belonging to the Glycoprotein IIb/IIIa Inhibitor acts as an Antiplatelet agent.

Tirofiban is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. Platelet aggregation inhibition is the reversible following cessation of the infusion of tirofiban.

The onset of action of Tirofiban is obtained within 10 minutes.

The duration of the Action of Tirofiban is approximately 4-6 hours.

Tirofiban is available in the form of an Injectable solution.

Tirofiban injection is given Intravenously.

Tirofiban is used in combination with heparin for decreasing the risks of major and life-threatening events or new episodes of heart attacks in patients suffering from non-ST elevation acute coronary syndrome (NSTE-ACS). Acute coronary syndrome (ACS) is caused by a sudden reduction or blockage of blood flow to the heart, causing chest pain and heart attacks. This medicine is used in patients who are to be managed medically. It is also used for the reduction of life-threatening adverse events in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or atherectomy.

Tirofiban is an antiplatelet agent belonging to Glycoprotein IIb/IIIa Inhibitor.

Tirofiban is a non-peptide tyrosine derivative that prevents fibrinogen binding to the glycoprotein (GP) IIb/IIIa receptor, leading to inhibition of platelet function, evidenced by its ability to inhibit ex vivo ADP-induced platelet aggregation and prolonged bleeding time.

Tirofiban is approved for use in the following clinical indications

• Acute coronary syndromes

Tirofiban is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).

Acute coronary syndromes

• Non-ST elevation acute coronary syndromes

IV: Loading dose: 25 mcg/kg administered over ≤5 minutes beginning after diagnostic coronary angiography, just before PCI; maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours.

• ST-elevation myocardial infarction (off-label use)

IV: Loading dose: 25 mcg/kg administered over ≤5 minutes beginning after diagnostic coronary angiography, just before PCI; maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours.

Tirofiban is available in various strengths as 250mg/mL and 50mg/mL.

Tirofiban is available in the form of an Injectable solution.

• Dosage Adjustment in Kidney Patient

CrCl >60 mL/minute: No dosage reduction is necessary.

CrCl ≤60 mL/minute: IV Loading dose: 25 mcg/kg administered over ≤5 minutes; Maintenance infusion: 0.075 mcg/kg/minute continued for up to 18 hours.

Tirofiban is contraindicated in patients with

• Severe hypersensitivity reaction to Tirofiban (i.e., anaphylactic reactions).
• 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.

• Bleeding

The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially at 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 the 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 the use of tirofiban. If during therapy platelet count decreases to <90,000/mm³, monitor platelet counts to exclude pseudo thrombocytopenia. 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.

It is not known whether tirofiban is excreted in human milk. However, significant levels of tirofiban were shown to be present in rat milk. Because many drugs are excreted in human milk, and because of the potential for adverse effects on the nursing infant, discontinue nursing or discontinue Tirofiban.

Tirofiban is not recommended for use in pregnant women unless necessary. There are no adequate and well-controlled studies on pregnant women. Tirofiban has been shown to cross the placenta in pregnant rats and rabbits. Studies with tirofiban HCl at intravenous doses up to 5 mg/kg/day (about 5 and 13 times the maximum recommended daily human dose for rats and rabbits, respectively, when compared on a body surface area basis) have revealed no harm to the fetus.

• Common Adverse effects

Hemorrhage, Bradycardia, coronary artery dissection, edema, vasodepressor syncope, Diaphoresis, Pelvic pain, Thrombocytopenia, Dizziness, Lower extremity pain, Swelling.

• Rare Adverse effects

Severe anemia, Anaphylaxis, severe hypersensitivity reaction.

• Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low-dose aspirin (81 mg/day or less).
• Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
• Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
• Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants.
• Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider the risks and benefits of this combination and monitor closely.
• 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.
• Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk of bleeding may be increased.
• 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.
• 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 the risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor.
• 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.
• Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased.
• 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.
• 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.
• 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.
• Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
• Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by the concurrent use of these agents.
• Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result.
• Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents.
• Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
• Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

The common side effects of Tirofiban include the following

• Common

Abdominal or stomach pain or swelling, Pain in the arm, back, or jaw, black or tarry stools, blood in the eyes, blood in the urine, bruising or purple areas on the skin, chest pain or discomfort, chest tightness or heaviness, coughing up blood, decreased alertness, fast or irregular heartbeat, headache, joint pain or swelling, nausea, nosebleeds.

• Rare

Bleeding gums, light-headedness, or fainting, pinpoint red spots on the skin, severe, unusual tiredness or weakness, slow heartbeat, swelling of the hands, ankles, feet, or lower legs, chills or fever, Cough, difficulty swallowing, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, skin rash, hives, or itching, trouble breathing.

• Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Tirofiban has been shown to cross the placenta in pregnant rats and rabbits. Studies with tirofiban HCl at intravenous doses up to 5 mg/kg/day (about 5 and 13 times the maximum recommended daily human dose for rats and rabbits, respectively, when compared on a body surface area basis) have revealed no harm to the fetus.

• Nursing Mothers

It is not known whether tirofiban is excreted in human milk. However, significant levels of tirofiban were shown to be present in rat milk. Because many drugs are excreted in human milk, and because of the potential for adverse effects on the nursing infant, discontinue nursing or discontinue Tirofiban.

• Pediatric Use

As per FDA, the safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

Of the total number of patients in controlled clinical studies of Tirofiban, 43% were 65 years and over, while 12% were 75 and over. With respect to efficacy, the effect of Tirofiban in the elderly (≥65 years) appeared like that seen in younger patients (<65 years). Elderly patients receiving Tirofiban with heparin or heparin alone had a higher incidence of bleeding complications than did younger patients, but the incremental risk of bleeding in patients treated with Tirofiban in combination with heparin compared to the risk in patients treated with heparin alone was similar regardless of age. No dose adjustment is recommended for the elderly population.

• In clinical trials, inadvertent overdosage with Tirofiban occurred in doses up to 2 times the recommended dose for initial infusion doses. Inadvertent overdosage occurred in doses up to 9.8 times the 0.15 mcg/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.
• Overdosage of Tirofiban should be treated by assessment of the patient’s clinical condition and cessation or adjustment of the drug infusion as appropriate. Tirofiban can be removed by hemodialysis.

Pharmacodynamic

Tirofiban prevents the blood from clotting during episodes of chest pain or a heart attack, or while the patient is undergoing a procedure to treat a blocked coronary artery. It is a non-peptide antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor and inhibits platelet aggregation. When administered intravenously, tirofiban inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner. When given according to the recommended regimen, >90% inhibition is attained by the end of the 30-minute infusion. Tirofiban has been recently shown in patients with unstable angina to reduce ischemic events at 48 hours following infusion when compared to standard heparin therapy.

Pharmacokinetics

• Absorption

Information is not available.

• Distribution

The volume of distribution of Tirofiban is about 22 to 42 L. The Plasma protein binding is approximately 65%.

• Metabolism and Excretion

It is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban. Half-life is about 2 hours.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020912s024,020913s022lbl.pdf
• https://www.rxlist.com/aggrastat-drug.htm#indications
• https://reference.medscape.com/drug/aggrastat-tirofiban-342185
• https://www.drugs.com/dosage/tirofiban.html
• https://go.drugbank.com/drugs/DB00775
• https://www.mims.com/philippines/drug/info/tirofiban?mtype=generic
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