tirofiban

General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
tye-roe-fye-ban


Trade Name(s)

  • Aggrastat

Ther. Class.
antiplatelet agents

Pharm. Class.
glycoprotein iib iiia inhibitors

Indications

To reduce the incidence of thrombotic cardiovascular events (death, MI, or refractory ischemia/repeat cardiac procedure in patients with non-ST elevation acute coronary syndrome [unstable angina/non-ST-elevation MI]).

Action

Decreases platelet aggregation by reversibly antagonizing the binding of fibrinogen to the glycoprotein IIb/IIIa binding site on platelet surfaces.

Therapeutic Effect(s):

Inhibition of platelet aggregation resulting in decreased incidence of new MI, death, or refractory ischemia with the need for repeat cardiac procedures.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Excreted mostly unchanged by the kidneys (65%); 25% excreted unchanged in feces.

Half-life: 2 hr.

TIME/ACTION PROFILE (effects on platelet function)

ROUTEONSETPEAKDURATION
IVrapid30 min†brief‡
†>90% inhibition of platelet aggregation at end of initial 30-min infusion.‡Inhibition is reversible following cessation of infusion.

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Active internal bleeding or history of bleeding within previous 30 days;
  • History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm;
  • History of thrombocytopenia during previous tirofiban therapy;
  • History of hemorrhagic stroke or other stroke within 30 days;
  • Major surgical procedure or severe physical trauma within 30 days;
  • History, symptoms, or other findings associated with aortic aneurysm;
  • Severe hypertension (systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg);
  • Concurrent use of other glycoprotein IIb/IIIa receptor antagonists;
  • Acute pericarditis;

Use Cautiously in:

  • Platelet count <150,000/mm3 ;
  • Hemorrhagic retinopathy;
  • Females (↑ risk of bleeding);
  • Severe renal impairment (↓ rate of infusion if CCr ≤60 mL/min);
  • OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
  • Lactation: Safety not established in breastfeeding;
  • Pedi:  Safety and effectiveness not established in children;
  • Geri:  ↑ risk of bleeding in older adults.

Adverse Reactions/Side Effects

Noted for patients receiving heparin and aspirin in addition to tirofiban

CV: bradycardia, coronary dissection, edema, vasovagal reaction

Derm: hives, rash, sweating

GI: nausea

Hemat: bleeding, thrombocytopenia

MS: leg pain

Neuro: headache, dizziness

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), fever, pelvic pain

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Drug-Natural Products:

↑ anticoagulant effect and bleeding risk with  anise,  arnica,  chamomile,  clove,  dong quai,  fenugreek,  feverfew,  garlic,  ginger,  ginkgo,  Panax ginseng,  licorice , and others.

Route/Dosage

IV (Adults): 25 mcg/kg within 5 min, then 0.15 mcg/kg/min for up to 18 hr.

Renal Impairment 
IV (Adults): CCr ≤60 mL/min– 25 mcg/kg within 5 min then 0.075 mcg/kg/min for up to 18 hr.

Availability (generic available)

Premixed infusion: 5 mg/100 mL 0.9% NaCl, 12.5 mg/250 mL 0.9% NaCl

Solution for injection: 250 mcg/mL

Assessment

  • Assess for bleeding. Most common is oozing from the arterial access site for cardiac catheterization. Arterial and venous punctures, IM injections, and use of urinary catheters, nasotracheal intubation, and nasogastric tubes should be minimized. Noncompressible sites for IV access should be avoided. If bleeding cannot be controlled with pressure, discontinue tirofiban and heparin immediately.
  • During vascular access, avoid puncturing posterior wall of femoral artery. Maintain bedrest with head of bed elevated 30° and affected limb restrained in a straight position while the vascular sheath is in place. Heparin should be discontinued for 3–4 hr and activated clotting time (ACT) <180 sec or activated partial thromboplastin time (aPTT) <45 sec prior to pulling the sheath. Use compressive techniques to obtain hemostasis and monitor closely. Sheath hemostasis should be maintained for >4 hr before discharge from the hospital.
  • Monitor for signs of thrombocytopenia (chills, low-grade fever) during therapy.

Lab Test Considerations:

Assess hemoglobin, hematocrit, and platelet count prior to tirofiban therapy, within 6 hr following loading infusion, and at least daily during therapy (more frequently if evidence of significant decline). May cause ↓ hemoglobin and hematocrit.

  • If platelet count ↓ to <90,000/mm3 , perform additional platelet counts to rule out pseudothrombocytopenia. If thrombocytopenia is confirmed, tirofiban and heparin should be discontinued and condition monitored and treated.
  • To monitor unfractionated heparin, assess aPTT 6 hr after the start of heparin infusion. Adjust heparin to maintain aPTT at approximately 2 times control.
  • May cause presence of urine and fecal occult blood.

Implementation

  • Do not confuse Aggrastat (tirofiban) with argatroban.
  • High Alert: Use of antiplatelet medications has resulted in patient harm and/or death from internal hemorrhage or intracranial bleeding. Have second practitioner independently check original order, dosage calculations, and infusion pump settings.
  • Most patients receive heparin and aspirin concurrently with tirofiban.

    • Do not administer solutions that are discolored or contain particulate matter. Discard unused portion.

IV Administration

  • IV Push:  Withdraw bolus dose from 15 mL premixed bolus vial into a syringe; may also be administered from the 100 mL premixed vial or from the 250 mL premixed bag. Do not dilute. Administer within 5 min via syringe or IV pump. Immediately following bolus dose, administer maintenance infusion from the 100 mL premixed vial or 250 mL premixed bag via an IV pump. Discard any unused portion left in the vial or bag.
  • Intermittent Infusion:   Diluent:  Tirofiban injection premix is ready for administration and dose not require any further dilution. Concentration: 50 mcg/mL.
  • Rate: Based on patient's weight (see Route/Dosage section).
  • Y-Site Compatibility:
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    • cangrelor
  • Y-Site Incompatibility:
    • amphotericin B lipid complex
    • dantrolene
    • diazepam
    • MORE...
      • phenytoin

Patient/Family Teaching

  • Explain purpose of tirofiban to patient.
  • Instruct patient to notify health care professional immediately if any bleeding is noted.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding.

Evaluation/Desired Outcomes

Inhibition of platelet aggregation resulting in decreased incidence of new MI, death, or refractory ischemia with the need for repeat cardiac procedures.

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