Uses for Tirofiban

Unstable Angina and Non-ST-Segment Elevation MI (NSTEMI)

Adjunct to anticoagulant therapy (e.g., heparin [referring throughout this

monograph to unfractionated heparin], low molecular weight heparin), aspirin,
and/or clopidogrel to reduce risk of acute cardiac ischemic events (death and/or MI)
in patients with non-ST-segment elevation acute coronary syndrome (i.e., unstable
angina or NSTEMI), including those who are to receive medical management or to
undergo PCI.1 5 6 21 91

Adjunctive therapy with a GP IIb/IIIa-receptor inhibitor can reduce the incidence of

cardiac ischemic events, including subsequent MI and death, in patients with nonST-segment-elevation acute coronary syndromes.5 6 11 35 36 42 46 51 71 72 73 80
83 84 85 91
The American College of Cardiology Foundation (ACCF) and AHA recommend either
clopidogrel or IV administration of a GP IIb/IIIa-receptor inhibitor in addition to
aspirin therapy prior to diagnostic angiography (upstream) in patients in whom an
initial invasive management strategy is planned; eptifibatide or tirofiban is the
preferred GP IIb/IIIa-receptor inhibitor for this use.991

The American College of Chest Physicians (ACCP) states that a clear risk-benefit
profile has not been established for the use of GP IIb/IIIa-receptor inhibitors in
patients with acute coronary syndromes who are not routinely scheduled for early
revascularization.1016

In patients undergoing PCI, ACCF, AHA, and the Society for Cardiovascular
Angiography and Intervention (SCAI) state that administration of a GP IIb/IIIareceptor inhibitor at the time of PCI may be used as an adjunct to heparin in those
with high-risk features (e.g., elevated troponin) who are not receiving bivalirudin
and are not adequately pretreated with clopidogrel.994

Regarding choice of GP IIb/IIIa-receptor inhibitor in patients undergoing PCI, IV

abciximab, double-bolus IV eptifibatide, and high-dose tirofiban by direct IV

injection all produce a high degree of platelet inhibition and reduce ischemic
complications.994

Tirofiban and eptifibatide not recommended by AHA in women with non-ST-segment

elevation acute coronary syndromes who are at lower risk for adverse events and
are managed with a conservative strategy, because of little demonstrated benefit
and possible detrimental effects.109

ACCF, AHA, SCAI, and other experts currently do not recommend routine use of GP
IIb/IIIa-receptor inhibitors in patients with ST-segment elevation MI (STEMI)
undergoing PCI; however, selective use of these drugs as an adjunct to heparin may
be reasonable in certain high-risk patients (e.g., those with large anterior MI and/or
large thrombus).994 1016

Tirofiban Dosage and Administration

General

Administer as soon as possible following diagnosis.21 91

Discontinue at least 46 hours prior to CABG.21 91
Adjunctive Antithrombotic Therapy

In clinical trials, almost all patients receiving tirofiban also received concomitant
aspirin and/or heparin.1 5 6 11 14 Tirofiban and heparin may be administered
through the same IV line.1
Aspirin: In clinical studies, patients received 300325 mg daily for at least 48 hours
after randomization or within 12 hours prior to PCI, unless the drug was
contraindicated; some patients received aspirin indefinitely.1 5 6 11 14
ACCF/AHA/SCAI recommends aspirin 325 mg prior to PCI in patients not already
receiving maintenance aspirin therapy.994 Patients already receiving maintenance
aspirin therapy should receive 81325 mg before the procedure.994

P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist: A loading dose of

clopidogrel, prasugrel, or ticagrelor also is recommended in patients undergoing PCI
with stent placement.994
Heparin during medical management: In clinical studies, patients received an IV
loading dose of 5000 units followed by continuous IV infusion of 1000 units/hour.1 5
6 (See Laboratory Monitoring under Cautions.)
Heparin prior to PCI: In clinical studies, patients undergoing PCI after at least 48
hours of medical management received an IV loading dose of 50007500 units
followed by continuous IV infusion of 1000 units/hour titrated to an aPTT
approximately 2 times the control value with additional IV injections of heparin as
needed. (See Laboratory Monitoring under Cautions.)1 6
Heparin prior to urgent PCI: In a clinical study, patients at high risk for abrupt
closure of the affected coronary artery who underwent urgent or emergency PCI
received an IV loading dose of 10,000 units (body weight 70 kg) or 150 units/kg
(body weight <70 kg).1 11 37 44 Additional injections during PCI were administered
to maintain target activated clotting time (ACT) between 300400 seconds.1 11 37
44
The manufacturer and other experts suggest use of lower dosages of concomitant
IV heparin (5070 units/kg) prior to PCI and targeted to an ACT of 200 seconds.1
18 35 44 53 71 74 77 80 81 95 96 (See Laboratory Monitoring under Cautions.)
Postprocedural use of heparin not recommended.6 11 42 52 53
Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion using either diluted injection concentrate or premixed

injection in plastic (IntraVia) containers.1 1

Discard unused portion.1

The plastic container of the premixed injection may be somewhat opaque because
of moisture absorption during sterilization; this opacity will diminish gradually.1

Do not introduce additives into the injection container.1

Do not use the plastic IV container in series connections with other plastic
containers; such use may result in air embolism.1

Dilution

Tirofiban hydrochloride injection concentrate for IV infusion must be diluted to 50

mcg/mL (the same concentration as the premixed injection) before administration.1

Prepare injection concentrate for infusion by withdrawing and discarding 50 or 100

mL of solution from a 250- or 500-mL bag, respectively, of 0.9% sodium chloride or
5% dextrose injection and replacing this volume with an equivalent volume (i.e., 50
or 100 mL, respectively) of tirofiban hydrochloride injection to achieve a final
concentration of 50 mcg/mL.1 21

Alternatively, a vial labeled as containing 5 mg of tirofiban may be added to a 100

mL bag of 0.9% sodium chloride injection or 5% dextrose injection.1

Mix solutions well prior to infusion.1

Rate of Administration

Administer as a continuous infusion.1 20 21 91

Dosage

Available as tirofiban hydrochloride; dosage expressed in terms of tirofiban.1

Adults

Unstable Angina and NSTEMI

IV

Patients receiving medical therapy: IV loading dose of 0.4 mcg/kg per minute for 30
minutes given as soon as possible after diagnosis, followed by continuous IV
infusion of 0.1 mcg/kg per minute for at least 2448 hours.21 91

Patients who undergo PCI: IV loading dose of 0.4 mcg/kg per minute for 30 minutes
followed by continuous IV infusion of 0.1 mcg/kg per minute given during
angiography and for 1224 hours after angioplasty or atherectomy.1 20 21 91

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1 20

Renal Impairment

In patients with severe renal impairment (i.e., Clcr 30 mL/minute), decrease the
usual loading and maintenance rate of infusion by 50%.1

Geriatric Patients

Dosage adjustment not required.1

Cautions for Tirofiban

Contraindications

Active internal bleeding or history of bleeding diathesis 1 5 6 14 20 21 91 within

previous 30 days.1 20 21 91
History of intracranial hemorrhage, intracranial neoplasm, arteriovenous
malformation, or aneurysm.1 52
History of thrombocytopenia following prior exposure to tirofiban.1 5 6 11 20 52
History of stroke within 30 days or any history of hemorrhagic stroke.1 5 6 11 14 20
52
Recent (within 30 days) major surgery or severe physical trauma.1 5 20 52
History, symptoms, or findings suggestive of aortic dissection.1 20
Severe uncontrolled hypertension (SBP >180 or DBP >110 mm Hg).1 5 20
Concomitant therapy with another parenteral GP IIb/IIIa-receptor inhibitor.1 20
Acute pericarditis.1 20
Known hypersensitivity to tirofiban or any ingredient in the formulation.1 20
Warnings/Precautions

Warnings

Hematologic Effects

Risk of major bleeding (e.g., intracranial hemorrhage, GU or GI bleeding, bleeding at

arterial access site) and minor bleeding (e.g., spontaneous gross hematuria,

spontaneous hematemesis); may require blood or platelet transfusions.1 5 6 11 20

21 91 (See Bleeding Precautions and also see Laboratory Monitoring under
Cautions.)

Pulmonary alveolar hemorrhage, spinal-epidural hematoma, retroperitoneal

bleeding, and hemopericardium reported rarely.1

Fatal hemorrhage reported rarely.1

Use with caution in patients with platelet count <150,000/mm3, anemia

(hemoglobin <1012 g/dL), hemorrhagic retinopathy, and those requiring chronic
hemodialysis.1 20 91

Use with caution in patients receiving other drugs that affect hemostasis (e.g.,
thrombolytic agents, oral anticoagulants, NSAIAs, dipyridamole, ticlopidine, and
clopidogrel).1 20 21 91 (See Specific Drugs under Interactions.)

If bleeding cannot be controlled by pressure, discontinue tirofiban and concomitant

heparin.1 20

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and other severe allergic reactions reported on the first day of infusion,
during initial treatment, and during readministration of the drug.1 21

Severe allergic reactions sometimes associated with severe thrombocytopenia

(platelet counts <10,000/mm3).1

General Precautions

Bleeding Precautions

To reduce risk of bleeding, adhere to strict anticoagulation guidelines; use a short

course of low-dose, weight-adjusted heparin; avoid vascular and other trauma;
carefully manage vascular (e.g., femoral artery) access site; and monitor all
potential bleeding sites during and following treatment.1 5 6 11 21 91

In patients undergoing PCI, use caution in the placement, maintenance, and

removal of vascular access sheath; avoid femoral vein sheath placement.1 18 35 37
42 46 52 When inserting sheath, puncture only anterior wall of femoral artery; avoid
Seldinger (through and through) technique.1 18 20 52 77 81 Observe appropriate
precautions while sheath is in place (e.g., complete bed rest, elevation of head
30, restrain limb in which sheath is inserted, frequent monitoring of vascular
access site and distal pulse in the involved limb).1 18 19 20 52 Following PCI,
consider early sheath removal (during tirofiban IV infusion).1 Prior to removal of
sheath, discontinue heparin for 34 hours and allow aPTT to return to <45 seconds
or ACT to <180 seconds.1 11 14 20 30 41 52 53 70 Discontinue tirofiban and
heparin and achieve hemostasis (by applying pressure to femoral artery for at least
2030 minutes after sheath removal18 19 ) at least 4 hours before hospital
discharge.1 20 Measure and monitor hematomas for enlargement.18

To avoid vascular and other trauma, minimize needle punctures (e.g., arterial, IM,
IV, lumbar, sub-Q, intradermal), cutdown sites, and use of nasotracheal intubation,
nasogastric tubes, urinary catheters,1 18 20 and automatic BP cuffs18 during and
following treatment;1 18 avoid establishment of IV access at noncompressible sites
(e.g., subclavian or jugular veins);1 18 consider using an indwelling venipuncture
device (e.g., heparin lock) for drawing blood; document and monitor vascular
puncture sites; and remove dressings gently and carefully.18

Thrombocytopenia

Thrombocytopenia reported.1 5 32 37 43 44 45 50 52 Severe thrombocytopenia

(platelet count <20,000/mm3) reported less frequently than with abciximab.18 30
32 35 37 44 50 53

Determine platelet counts prior to treatment and periodically (e.g., within the first 6
hours of the loading infusion, and daily thereafter) during concomitant tirofiban and
heparin therapy.1 11 20 43 44 Consider possibility of pseudothrombocytopenia or
heparin-induced thrombocytopenia in patients receiving concomitant heparin
therapy.1 20 35 37 52 (See Thrombocytopenia under Cautions.)

If true thrombocytopenia is verified, discontinue tirofiban and initiate appropriate

treatment and monitoring.1 Thrombocytopenia usually reversible following
discontinuance of GP IIb/IIIa-receptor inhibitors and anticoagulant (heparin) therapy;
consider platelet transfusions for the management of severe thrombocytopenia.35
37 43 52

Use with caution in patients with platelet count <150,000/mm3;1 20

contraindicated in patients with a history of thrombocytopenia following prior
exposure to tirofiban.1 5 6 11 20 52

Laboratory Monitoring

Prior to administration, within the first 6 hours of the loading infusion and at least
daily thereafter, obtain hematocrit and hemoglobin,1 11 20 35 43 44 and platelet
counts.1 11 20 35 43 44

Closely monitor ACT or aPTT.1 30 52 70 Monitor aPTT 6 hours after the start of the
heparin infusion and maintain at 5070 seconds or approximately 2 times the
control value unless PCI is to be performed.1 6 30 In patients undergoing PCI,
measure the ACT.21 52 70 In patients undergoing PCI in clinical studies, ACT was
maintained between 300400 seconds during PCI;1 11 37 44 ACCP suggests
targeting ACT between 200250 seconds to reduce risk of major bleeding.1 18 35
44 53 71 74 77 80 81 95 96 Monitor aPTT or ACT prior to arterial sheath removal; do
not remove sheath unless aPTT <45 seconds or ACT <180 seconds.1 30 41 53 70

Determine platelet counts prior to administration, within the first 6 hours of the
loading infusion and at least daily thereafter.1 11 20 43 44 Perform additional

platelet counts if a patient experiences a reduction in platelet count to

<90,000/mm3 to exclude the possibility of pseudothrombocytopenia.1 18 90

Specific Populations

Pregnancy

Category B.1

Lactation

Distributed into milk in rats;1 not known whether distributed into human milk.1
Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1 20

Geriatric Use

No substantial differences in efficacy relative to younger adults.1 However,

increased incidence of bleeding complications and non-bleeding adverse events in
some studies.1 20

Women

Increased incidence of minor bleeding complications and non-bleeding adverse

events in some studies.1 109

Hepatic Impairment

Clearance not affected in patients with mild to moderate hepatic impairment;1 20

information on plasma clearance limited in patients with severe hepatic impairment
since these patients were excluded from participation in clinical studies.21

Renal Impairment

Substantially decreased clearance (>50%) in patients with severe renal impairment

(i.e., Clcr 30 mL/minute), including patients requiring hemodialysis;1 reduced
dosage recommended in such patients.1 20 (See Renal Impairment under Dosage
and Administration.)

Use with caution in patients requiring chronic hemodialysis.1 20 91

Common Adverse Effects

Bleeding,1 pelvic pain,1 coronary artery dissection,1 bradycardia,1 leg pain,1

dizziness,1 edema/swelling, 1 vasovagal reaction,1 sweating.1

Tirofiban Pharmacokinetics

Absorption

Onset

Rapid onset;11 14 20 90% inhibition of platelet aggregation occurs by the end of

the IV loading infusion administration.1 20 21

Duration

Short duration of action;11 14 20 platelet aggregation persists during maintenance

infusion.1 20 21 Platelet function generally recovers within 48 hours following
discontinuance of infusion.1 20

Distribution

Extent

Distributed into milk in rats and crosses the placenta in pregnant rats and rabbits.1
20 Not known whether tirofiban crosses the placenta or is distributed into milk in
humans.1 20

Plasma Protein Binding

Approximately 65%.1 4 20

Elimination

Metabolism

Metabolism appears limited.1 20

Elimination Route

Excreted in urine (65%) and in feces (25%) mainly as unchanged drug.1 20

Half-life

Approximately 1.22 hours.1 3 4 15 20 22 91

Special Populations

Plasma clearance may decrease substantially (>50%) in patients with severe renal
impairment (i.e., Clcr 30 mL/minute and those requiring hemodialysis) 1 (See
Renal Impairment under Dosage and Administration.)

Removed by hemodialysis.1 20

Plasma clearance decreased approximately 1926% in geriatric patients.20

Stability

Storage

Parenteral

For Injection, Concentrate, for IV Infusion

25C (may be exposed to 1530C).1 20 Do not freeze; protect from light.1 20

Contains no preservative; discard unused solution.1

Injection, for IV Infusion

25C (may be exposed to 1530C).1 Do not freeze; protect from light.1

Contains no preservative; discard unused solution.1

Compatibility

For information on systemic interactions resulting from concomitant use, see

Interactions.

Parenteral

Solution CompatibilityHID

Compatible
Dextrose 5% in sodium chloride 0.45%
Dextrose 5% in water
Sodium chloride 0.9%
Drug Compatibility

Y-Site Compatibility1HID
Compatible
Amiodarone HCl
Atropine sulfate
Bivalirudin
Dobutamine HCl

Dopamine HCl
Epinephrine HCl
Famotidine HCl
Furosemide
Heparin sodium
Lidocaine HCl
Midazolam HCl
Morphine sulfate
Nitroglycerin
Potassium chloride
Propranolol HCl
Incompatible1 HID
Diazepam
Actions

Binds selectively to platelet GP IIb/IIIa receptors and reversibly inhibits platelet

aggregation (by preventing binding of fibrinogen, von Willebrand factor, and other
adhesive ligands to GP IIb/IIIa receptors).1 11 16 17 22 24 43 45
Modest effect on hemostatic indices (e.g., bleeding times);1 2 normal hemostasis
restored more rapidly than with abciximab.8 31 32 35 74 91
Usually does not affect aPTT when administered as monotherapy.5 6
Advice to Patients

Risk of serious bleeding or hemorrhage.1

Importance of close laboratory monitoring.1
Importance of informing clinicians of existing or contemplated concomitant therapy,
including prescription and OTC drugs and dietary or herbal supplements, as well as
any concomitant illnesses (e.g., cardiovascular disease).1

Importance of women informing clinicians if they are or plan to become pregnant or

plan to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See
Cautions.)
Preparations

Excipients in commercially available drug preparations may have clinically

important effects in some individuals; consult specific product labeling for details.

Tirofiban Hydrochloride
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Parenteral
For injection, concentrate, for IV infusion
250 mcg (of tirofiban) per mL (5 and 12.5 mg)
Aggrastat
Medicure
Tirofiban Hydrochloride in Sodium Chloride
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Parenteral

Injection, for IV infusion

50 mcg (of tirofiban) per mL (5 and 12.5 mg) in 0.9% Sodium Chloride
Aggrastat Premixed in Iso-osmotic Sodium Chloride Injection (in IntraVia flexible
container)
Medicure