Tirofiban

Tirofiban is an anticoagulant that prevents platelets from clumping together into blood clots. It can reduce the risk of heart attack and premature death. The most common side effect associated with tirofiban use is excessive bleeding. Because of this, often tirofiban is not used in patients already at risk of abnormal, excessive bleeding. The Food and Drug Administration (FDA) approved tirofiban in May of 1998.

This scanning electron microscope image shows a red blood cell (left), a platelet (center), and a T-lymphocyte (right). Source: Wikimedia Commons

Other Names

Tirofiban is sold under the name Aggrastat. It is marketed by Medicure Pharma in the United States and by Merck Pharmaceuticals in other countries.

Uses/Indications

Tirofiban is an anti-platelet and anticoagulant. Its actions prevent the coagulation (clotting) of blood. Tirofiban is often used in patients with coronary artery disease (CAD). It is used to treat acute coronary syndrome, which is characterized by unstable angina (chest pain) and heart attack. Often it is used during a procedure to enlarge blood vessels (angioplasty). By thinning the blood, tirofiban reduces the risk of heart attacks and reduces the risk of premature death. Acetylsalicylic acid (aspirin) and heparin are often used in combination with tirofiban to help reduce the risk of clotting.

How Tirofiban is Taken

Physicians infuse tirofiban intravenously (IV) at a concentration of 0.25 mg/ml (milligrams per milliliter). It is given initially at a high dose for 30 minutes (the induction phase). The dose is then decreased for the maintenance phase of treatment. The maintenance phase usually lasts 48 hours. The rate of infusion is often adjusted according to the weight of the patient.

How Tirofiban Works

Platelets coagulate, or form clots, by sticking together or to other surfaces such as a blood vessel wall or surgical implant. Platelet aggregation occurs by a cascade of events when clotting is needed, such as after a cut on the skin. The cascade is activated when a protein called fibrinogen binds to a glycoprotein IIb/IIIa receptor on the surface of a cell. Tirofiban is a glycoprotein IIb/IIIa inhibitor that blocks the receptor and prevents fibrinogen from binding.

How the Body Affects Tirofiban

The half-life of tirofiban, the time required for the concentration in the body to be reduced by half, is approximately two hours. Most of tirofiban is excreted in the urine. Tirofiban is not metabolized to a large extent, therefore, the drug is unlikely to affect the metabolism of other drugs.

In special populations

In elderly patients with CAD (over 65 years of age), the rate at which tirofiban is eliminated from the body is slightly slower than that of younger patients (less than 65 years of age). This reduction is unlikely to influence the effectiveness of tirofiban. Kidney disease reduces the elimination of tirofiban by over 50% because the drug is largely excreted in urine. Accordingly, the dosage is usually reduced in patients with kidney disease. Gender, race ethnicity, and liver damage do not influence elimination.

Side Effects

The most common side effect of tirofiban use is excessive bleeding. Major or minor bleeding occurs in fewer than 15% of patients. Blood transfusions are sometimes used to improve clotting. Some other common side effects include the following:

• Pelvic pain
• Slow heart rate
• Tear in the coronary artery
• Leg pain
• Dizziness

After tirofiban became available by prescription, rare cases of bleeding in various organs appeared, such as the brain or lungs. Cases of low platelet numbers (thrombocytopenia) have also been reported.

Risks and Precautions

Tirofiban is given at half the usual infusion rate in patients with kidney disease because compromised kidney function reduces elimination of the drug. It is used with caution in patients who have a low number of platelets, or who have bleeding tendencies.

Contraindications

Tirofiban is not used in patients who are at an increased risk of developing complications such as excessive bleeding. Accordingly, it is not used under the following conditions:

• Bleeding in the brain, brain tumor or ballooning of a blood vessel in the brain
• History of low platelet number due to treatment with tirofiban
• Injury to the aorta (large artery that carries blood from the heart)
• Pericarditis (inflammation of the sac surrounding the heart)
• Severe hypertension (high blood pressure)
• During treatment with eptifibatide (Integrilin)

Tirofiban is not used within 30 days of the following:

• Internal bleeding or a tendency towards bleeding
• Stroke
• Major surgery or trauma

Drug Interactions

Acetylsalicylic acid and heparin increase the risk of bleeding during treatment with tirofiban, but this does not prevent the use of this combination in many patients. The influence of other anticoagulant drugs, such as warfarin, on the effectiveness or safety of tirofiban is not known.

Overdose

Inadvertent overdoses have occurred in clinical trials. The doses were between two and ten times the recommended amount. The only adverse effect was bleeding. Excessive bleeding can be treated by lowering the dose and by using dialysis to remove tirofiban from the blood.

Research

In one study, tirofiban in combination with acetylsalicylic acid and clopidogrel (Plavix) reduced platelet aggregation in patients with heart attack undergoing angioplasty.^[1] Tirofiban also improved blood flow to the heart and reduced heart-related complications. Data suggests that a high dose of tirofiban is as effective as eptifibatide (Integrilin) in preventing platelet aggregation during angioplasty.^[2]

Sales

In 2005, sales of tirofiban reached approximately US$88 million in Europe. The sales in the United States in the same year were $10.9 million.

Interesting Fact

The venom of many snakes contains anticoagulants that help digest prey. Tirofiban is a synthetic drug based on an anticoagulant derived from the venom of the saw-scaled viper.

References

1. ↑ Fu XH, Hao QQ, Jia XW, et al. Effect of tirofiban plus clopidogrel and aspirin on primary percutaneous coronary intervention via transradial approach in patients with acute myocardial infarction. Chin Med J (Engl) 2008 Mar 20;121(6):522-7. Abstract | Full Text
2. ↑ Marmur JD, Poludasu S, Agarwal A, Manjappa N, Cavusoglu E. High-dose tirofiban administered as bolus-only during percutaneous coronary intervention. J Invasive Cardiol 2008 Feb;20(2):53-8. Abstract

External Links

Medicure Pharma: Aggrastat

Aggrastat Consumer Information