No

Antiplatelet Agent

In combination with heparin, is indicated for the treatment of acute coronary syndrome, including patients who are to be managed medically and those undergoing PTCA or atherectomy. In this setting, it has been shown to decrease the rate of a combined endpoint of death, new myocardial infarction or refractory ischemia/repeat cardiac procedure.

B

Hypersensitivity to tirofiban or any component; active internal bleeding or a history of bleeding diathesis within the previous 30 days; history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; history of thrombocytopenia following prior exposure; history of CVA within 30 days or any history of hemorrhagic stroke; major surgical procedure or severe physical trauma within the previous month; history, symptoms, or findings suggestive of aortic dissection; severe hypertension (systolic BP >180 mm Hg and/or diastolic BP >1110 mm Hg); concomitant use of another parenteral GP IIb/IIIa inhibitor; acute pericarditis

Bleeding is the most common complication. Watch closely for bleeding, especially the arterial access site for the cardiac catheterization. Prior to pulling the sheath, heparin should be discontinued for 3-4 hours and ACT <180 seconds or APTT <45 seconds. Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding. Use with extreme caution in patients with platelet counts <150,000/mm³ and in patients with diabetic retinopathy. Use caution with administration of other drugs affecting hemostasis. Adjust the dose with severe renal dysfunction (Cl_cr <30 mL/minute). The use of tirofiban, aspirin and heparin together causes more bleeding than aspirin and heparin alone. Do not administer in the same IV line as diazepam.

Bleeding is the major drug-related adverse effect. Patients received background treatment with aspirin and heparin. Major bleeding was reported in 1.4% to 2.2%; minor bleeding in 10.5% to 12%; transfusion was required in 4.0% to 4.3%.

Cardiovascular: Bradycardia (4%), coronary artery dissection (5%), edema (2%)

Central nervous system: Dizziness (3%), fever (>1%), headache (>1%), vasovagal reaction (2%)

Gastrointestinal: Nausea (>1%)

Genitourinary: Pelvic pain (6%)

Hematologic: Thrombocytopenia: <90,000/mm³ (1.5%), <50,000/mm³ (0.3%)

Neuromuscular & skeletal: Leg pain (3%)

Miscellaneous: Diaphoresis (2%)

<1% (Limited to important or life-threatening symptoms): Intracranial bleeding (0.0% to 0.1%), GI bleeding (0.1% to 0.2%), retroperitoneal bleeding (0.0% to 0.6%), GU bleeding (0.0% to 0.1%), hemopericardium, rash, hives

Most frequent manifestation of overdose is bleeding; treatment is cessation of therapy and assessment of transfusion. Tirofiban has a relatively short half-life and its platelet effects dissipate rather quickly. However, when immediate reversal is required, platelet transfusions can be useful. Tirofiban is dialyzable.

Cephalosporins which contain the MTT side chain may theoretically increase the risk of hemorrhage.

Drugs which affect platelet function (eg, aspirin, NSAIDs, dipyridamole, ticlopidine, clopidogrel) may potentiate the risk of hemorrhage.

Heparin and aspirin: Use with aspirin and heparin is associated with an increase in bleeding over aspirin and heparin alone. However, the concurrent use of aspirin and heparin has also improved the efficacy of tirofiban.

Levothyroxine and omeprazole increase tirofiban clearance; however, the clinical significance of this interaction remains to be demonstrated.

Thrombolytic agents theoretically may increase the risk of hemorrhage.

Warfarin and oral anticoagulants: Risk of bleeding may be increased during concurrent therapy.

Other IIb/IIIa antagonists: Avoid concomitant use of other injectable glycoprotein IIb/IIIa antagonists (see Contraindications).

Store at 25°C (77°F); do not freeze. Protect from light during storage.

A reversible antagonist of fibrinogen binding to the 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 by the end of the 30-minute infusion. Platelet aggregation inhibition is reversible following cessation of the infusion.

Distribution: 35% unbound

Metabolism: Minimal

Elimination: Primarily unchanged drug; 65% in urine, 25% in feces; clearance is reduced in elderly patients by 19% to 26%

Adults: I.V.: Initial rate of 0.4 mcg/kg/minute for 30 minutes and then continued at 0.1 mcg/kg/minute; dosing should be continued through angiography and for 12-24 hours after angioplasty or atherectomy.

30-37 kg: 30-minute load: 16 mL/hour; maintenance infusion: 4 mL/hour

38-45 kg: 30-minute load: 20 mL/hour; maintenance infusion: 5 mL/hour

46-54 kg: 30-minute load: 24 mL/hour; maintenance infusion: 6 mL/hour

55-62 kg: 30-minute load: 28 mL/hour; maintenance infusion: 7 mL/hour

63-70 kg: 30-minute load: 32 mL/hour; maintenance infusion: 8 mL/hour

71-79 kg: 30-minute load: 36 mL/hour; maintenance infusion: 9 mL/hour

80-87 kg: 30-minute load: 40 mL/hour; maintenance infusion: 10 mL/hour

88-95 kg: 30-minute load: 44 mL/hour; maintenance infusion: 11 mL/hour

96-104 kg: 30-minute load: 48 mL/hour; maintenance infusion: 12 mL/hour

105-112 kg: 30-minute load: 52 mL/hour; maintenance infusion: 13 mL/hour

113-120 kg: 30-minute load: 56 mL/hour; maintenance infusion: 14 mL/hour

121-128 kg: 30-minute load: 60 mL/hour; maintenance infusion: 15 mL/hour

128-137 kg: 30-minute load: 64 mL/hour; maintenance infusion: 16 mL/hour

138-145 kg: 30-minute load: 68 mL/hour; maintenance infusion: 17 mL/hour

146-153 kg: 30-minute load: 72 mL/hour; maintenance infusion: 18 mL/hour

Tirofiban dosing in patients with renal dysfunction:

30-37 kg: 30-minute load: 8 mL/hour; maintenance infusion: 2 mL/hour

38-45 kg: 30-minute load: 10 mL/hour; maintenance infusion: 3 mL/hour

46-54 kg: 30-minute load: 12 mL/hour; maintenance infusion: 3 mL/hour

55-62 kg: 30-minute load: 14 mL/hour; maintenance infusion: 4 mL/hour

63-70 kg: 30-minute load: 16 mL/hour; maintenance infusion: 4 mL/hour

71-79 kg: 30-minute load: 18 mL/hour; maintenance infusion: 5 mL/hour

80-87 kg: 30-minute load: 20 mL/hour; maintenance infusion: 5 mL/hour

88-95 kg: 30-minute load: 22 mL/hour; maintenance infusion: 6 mL/hour

96-104 kg: 30-minute load: 24 mL/hour; maintenance infusion: 6 mL/hour

105-112 kg: 30-minute load: 26 mL/hour; maintenance infusion: 7 mL/hour

113-120 kg: 30-minute load: 28 mL/hour; maintenance infusion: 7 mL/hour

121-128 kg: 30-minute load: 30 mL/hour; maintenance infusion: 8 mL/hour

128-137 kg: 30-minute load: 32 mL/hour; maintenance infusion: 8 mL/hour

138-145 kg: 30-minute load: 34 mL/hour; maintenance infusion: 9 mL/hour

146-153 kg: 30-minute load: 36 mL/hour; maintenance infusion: 8 mL/hour

Dosing adjustment in severe renal impairment: Cl_cr <30 mL/minute: Reduce dose to 50% of normal rate.

Platelet count, persistent reductions <90,000/mm³ may require interruption or discontinuation of infusion. Hemoglobin and hematocrit should be monitored prior to treatment, within 6 hours following loading infusion, and at least daily thereafter during therapy. Because tirofiban requires concurrent heparin therapy, aPTT levels should also be followed. Monitor vital signs and laboratory results prior to, during, and after therapy. Assess infusion insertion site during and after therapy (every 15 minutes or as institutional policy). Observe and teach patient bleeding precautions (avoid invasive procedures and activities that could result in injury). Monitor closely for signs of unusual or excessive bleeding (eg, CNS changes, blood in urine, stool, or vomitus, unusual bruising or bleeding). Breast-feeding is contraindicated.

Tirofiban and other IIb/IIIa inhibitors appear to have a beneficial effect in decreasing cardiovascular death and the need for revascularization when used in patients with coronary artery disease. This is not necessarily a class effect. Some inhibitors (eg, sibrafiban) have not demonstrated clear cardiovascular benefit. Specifically, the benefits of IIb/IIIa inhibitors are evident when used with aspirin either with or in comparison to heparin in patients with unstable angina. IIb/IIIa inhibitors also decrease the frequency of cardiovascular presentations when used prior to angioplasty or arthrectomy. The benefits in terms of cardiovascular event reduction need to be balanced against a small but significantly increased risk of bleeding.

May cause dizziness

Contraindicated in patients with a recent stroke (within 30 days)

No information available to require special precautions

No effects or complications reported

Emergency use may dictate depth of patient education. This medication can only be administered I.V. You will have a tendency to bleed easily following this medication. Use caution to prevent injury (use electric razor, use soft toothbrush, use caution with sharps). If bleeding occurs, apply pressure to bleeding spot until bleeding stops completely. Report unusual bruising or bleeding (eg, blood in urine, stool, or vomitus, bleeding gums, vaginal bleeding, nose bleeds); unusual and persistent fever; dizziness or changes in vision; back, leg, or pelvic pain; or persistent nausea or vomiting. Breast-feeding precautions: Do not breast-feed.

Injection: 50 mcg/mL (500 mL); 250 mcg/mL (50 mL)