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Tirofiban


General


Pronunciation

(tye roe FYE ban)


Brand Names: U.S.

  • Aggrastat

Indications


Use: Labeled Indications

Unstable angina/non-ST-elevation myocardial infarction: Decrease the rate of thrombotic cardiovascular events (combined end point of death, MI, or refractory ischemia/repeat cardiac procedure) in patients with non-ST-elevation acute coronary syndrome (unstable angina/non-ST-elevation myocardial infarction [UA/NSTEMI]).


Contraindications


Severe hypersensitivity reaction (ie, anaphylactic reaction) to tirofiban or any component of the formulation; 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


Dosing and Administration


Dosing: Adult

Unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI): IV: Loading dose: 25 mcg/kg administered over 5 minutes or less; Maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours

Percutaneous coronary intervention (PCI): IV: Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute continued for up to 18 hours (ACCF/AHA [Anderson 2013]; ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2004)

Stable ischemic heart disease (high-risk features) undergoing elective PCI (off-label use): Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute; was continued for up to 48 hours in the clinical trial (ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2004). Note: Reserve for patients who were not pretreated with clopidogrel or who are undergoing elective PCI with stent implantation with adequate clopidogrel pretreatment (ACCF/AHA/SCAI [Levine 2011]).

ST-elevation myocardial infarction (STEMI) undergoing primary PCI (off-label use): IV Loading dose: 25 mcg/kg administered over 5 minutes or less at the time of PCI; Maintenance infusion: 0.15 mcg/kg/minute in combination with heparin or bivalirudin in selected patients; was continued for 18-24 hours in clinical trials (ACCF/AHA [O 'Gara 2013]; ACCF/AHA/SCAI [Levine 2011]; Valgimigli 2008; Van 't Hof 2008)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

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

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


Administration

IV: Administer loading dose over 5 minutes or less, followed by a continuous infusion. Note: Clinical trials administered tirofiban loading dose over a period of 3 minutes (Valgimigli 2004; Valgimigli 2005; Valgimigli 2009).


Storage

Store at 25 ‚ °C (77 ‚ °F); excursions are permitted between 15 ‚ °C and 30 ‚ °C (59 ‚ °F and 86 ‚ °F); do not freeze. Protect from light during storage.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Aggrastat: 50 mcg/mL (100 mL, 250 mL)


Compatibility

Y-site administration: Incompatible with diazepam.


Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

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. Monitor therapy

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 risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

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. Monitor therapy

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy


Monitoring Parameters

Platelet count (baseline; 6 hours after initiation and daily thereafter during therapy). Monitor platelet counts more closely in patients who have had previous exposure to glycoprotein IIb/IIa antagonists. Persistent reductions of platelet counts <90,000/mm3 may require interruption or discontinuation of infusion; hemoglobin and hematocrit; signs of bleeding.

Standard post-PCI assessment if patient undergoes PCI (eg, monitoring vascular access site, monitoring for chest pain and signs of bleeding)


Adverse Reactions


Bleeding is the major drug-related adverse effect. Patients received background treatment with aspirin and heparin. Adverse reactions reported are derived from both the high-dose bolus regimen and the dosing regimen used in studies that established the effectiveness of tirofiban. Frequency not always defined.

>10%: Hematologic & oncologic: Minor hemorrhage (TIMI criteria minor bleeding; 10.5% to 12%; transfusion required: 4% to 4.3%)

1% to 10%:

Cardiovascular: Coronary artery dissection (5%), bradycardia (4%), edema (2%), vasodepressor syncope (2%)

Central nervous system: Dizziness (3%), headache (>1%)

Dermatologic: Diaphoresis (2%)

Gastrointestinal: Nausea (>1%)

Genitourinary: Pelvic pain (6%)

Hematologic & oncologic: Major hemorrhage (TIMI criteria major bleeding: 1.4% to 2.2%; including hematoma [femoral]: 2% [Valgimigli, 2005], intracranial bleeding, GI bleeding, retroperitoneal bleeding [Aydin, 2003], GU bleeding, pulmonary alveolar hemorrhage [Guo, 2012], spinal-epidural hematoma), thrombocytopenia: <90,000/mm3 (1.5% to 1.9%), <50,000/mm3 (0.3% to 0.5%)

Neuromuscular & skeletal: Leg pain (3%)

Miscellaneous: Fever (>1%)

<1% (Limited to important or life-threatening): Anaphylaxis, hemopericardium, hypersensitivity


Warnings/Precautions


Special Populations: Renal Function Impairment

Plasma clearance is decreased by ~40% in patients with CrCl <60 mL/minute and more than 50% in patients with CrCl <30 mL/minute (including those requiring hemodialysis).


Warnings/Precautions

Concerns related to adverse effects:

- Bleeding: The most common complication is bleeding, including retroperitoneal, pulmonary, and spontaneous GI and/or GU bleeding; watch closely for bleeding, especially 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 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 use of tirofiban. If during therapy platelet count decreases to <90,000/mm3, monitor platelet counts to exclude pseudothrombocytopenia. 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 (Huxtable, 2006; Llevadot, 2000).

Disease-related concerns:

- Renal impairment: Dosage reduction of the maintenance infusion rate is necessary in patients with CrCl ≤60 mL/minute.

Other warnings/precautions:

- Percutaneous coronary intervention: Sheath removal: Prior to pulling the sheath, ACT should be <180 seconds or aPTT <50 seconds (ACCF/AHA/SCAI [Levine, 2011]). Use standard compression techniques after sheath removal. Watch the site closely afterwards for further bleeding.

- Surgery: Discontinue at least 2 to 4 hours prior to coronary artery bypass graft surgery (ACCF/AHA [Anderson, 2013]; ACCF/AHA [Hillis, 2011]).


Pregnancy Risk Factor

B


Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Information related to use in pregnancy is limited; successful use during pregnancy has been described in a case report (Boztosun, 2008).


Actions


Pharmacology

A reversible antagonist of fibrinogen binding to the glycoprotein (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 within 10 minutes after initiation. Platelet aggregation inhibition is reversible following cessation of the infusion.


Distribution

Vdss: 22 to 42 L


Metabolism

Negligible


Excretion

Urine (65%) and feces (25%) primarily as unchanged drug


Onset of Action

>90% inhibition of platelet aggregation (reversible after discontinuation) seen within 10 minutes


Half-Life Elimination

2 hours; Note: In ~90% of patients, ex vivo platelet aggregation returns to near baseline in 4 to 8 hours after discontinuation.


Protein Binding

65% (concentration dependent)


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any bleeding that is very bad or that will not stop) or injection site irritation or edema (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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