Aggrastat

Tirofiban is injected into a vein through an IV. A healthcare provider will give you this injection.

While using tirofiban, you may need frequent blood tests.

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Because you will receive tirofiban in a clinical setting, you are not likely to miss a dose.

Contraindications

Hypersensitivity, history of thrombocytopenia with tirofiban

Active/history of internal bleeding (within last 30 days), intracranial hemorrhage or neoplasm

History of stroke within last 30 days or any history of hemorrhagic stroke

AV malformation or aneurysm, aortic dissection, severe HTN, acute pericarditis

Current use of another parenteral glycoprotein IIb/IIIa inhibitor

Cautions

Platelets <150,000/cu.mm, hemorrhagic retinopathy, chronic HD

Rates of major bleeds with the recommended high-dose bolus (ie, 25 mcg/kg/min loading dose) were consistent with the rates observed in the PRISM-PLUS regimen (original dosage regimen); there was a trend toward greater bleeding in ST segment elevation myocardial infarction (STEMI) patients treated with fibrinolytics prior to administration tirofiban using the high-dose bolus during rescue PCI

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tirofiban increases your risk of bleeding, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have:

• easy bruising or bleeding (nosebleeds, bleeding gums);

• bleeding around your IV or catheter; or

• any bleeding that will not stop.

You may also have bleeding on the inside of your body, such as in your stomach or intestines. Call your doctor at once if you have bloody or tarry stools, or if you cough up blood or vomit that looks like coffee grounds. These could be signs of bleeding in your digestive tract.

Common side effects may include:

• dizziness;

• slow heart rate;

• leg pain, pelvic pain; or

• swelling, increased sweating.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General

• Administer as soon as possible following diagnosis.21 91

• Discontinue at least 4–6 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 300–325 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 81–325 mg before the procedure.994

• P2Y12-receptor antagonist: A loading dose of clopidogrel, prasugrel, or ticagrelor also is recommended in patients undergoing PCI with stent placement.994 995

• 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 5000–7500 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.1 6 (See Laboratory Monitoring under Cautions.)

• 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 300–400 seconds.1 11 37 44

• The manufacturer and other experts suggest use of lower dosages of concomitant IV heparin (50–70 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

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

Administer as a continuous infusion.1 20 21 91

Dosage

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

Adults

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 24–48 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 12–24 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

• 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.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

In the U.S.

• Aggrastat

Available Dosage Forms:

• Solution

Therapeutic Class: Platelet Aggregation Inhibitor

Pharmacologic Class: Glycoprotein IIb/IIIa Inhibitor

Tirofiban injection is used to prevent blood clots from forming in the arteries of the heart after certain types of chest pain and heart attacks. It may also be used in patients who are having certain heart and blood vessel procedures.

Tirofiban is an antiplatelet medicine. It reduces the chance that a harmful clot will form by preventing certain cells in the blood from clumping together.

This medicine is to be given only by or under the direct supervision of your doctor.

It is very important that your doctor check you at regular visits after you leave the hospital for any problems that may be caused by this medicine. Blood and urine tests will be needed to check for unwanted effects. Be sure to keep all appointments.

You may bleed and bruise more easily while you are using this medicine. Be extra careful to avoid injuries until the effects of the medicine have worn off.

Check with your doctor right away if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin. Avoid picking your nose. If you need to blow your nose, blow it gently.

You may be told to use a soft toothbrush or to shave with an electric razor (not a razor blade) for a few days after you have been given this medicine. This helps reduce the risk of bleeding.

Watch for any bleeding from open areas such as sites of needle punctures for drawing blood, giving shots, or putting in a catheter for a heart catheterization or angioplasty. Also check for blood in your urine or bowel movements. If you have any bleeding or injuries, tell your doctor right away.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

• It is used during a heart treatment to protect the arteries.
• It is used to lower the chance of heart attack, the need for some heart treatments, or blockage of a stent after a stent is placed in the heart.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• If you fall or hurt yourself, or if you hit your head, call your doctor right away. Talk with your doctor even if you feel fine.
• If you are 65 or older, use Aggrastat with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.

General Risk of Bleeding

Bleeding is the most common complication encountered during therapy with Aggrastat. Most bleeding associated with Aggrastat occurs at the arterial access site for cardiac catheterization. Minimize the use of traumatic or potentially traumatic procedures such as arterial and venous punctures, intramuscular injections, nasotracheal intubation, etc.

Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.

Thrombocytopenia

Profound thrombocytopenia has been reported with Aggrastat. Monitor platelet counts beginning about 6 hours after treatment initiation and daily thereafter. If the platelet count decreases to <90,000/mm3, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue Aggrastat and heparin. Previous exposure to a glycoprotein (GP) IIb/IIIa receptor antagonist may increase the risk of developing thrombocytopenia [see Adverse Reactions (6.1)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of Aggrastat has not been evaluated.

Tirofiban HCl was negative in the in vitro microbial mutagenesis and V-79 mammalian cell mutagenesis assays. In addition, there was no evidence of direct genotoxicity in the in vitro alkaline elution and in vitro chromosomal aberration assays. There was no induction of chromosomal aberrations in bone marrow cells of male mice after the administration of intravenous doses up to 5 mg tirofiban/kg (about 3 times the maximum recommended daily human dose when compared on a body surface area basis).

Fertility and reproductive performance were not affected in studies with male and female rats given intravenous doses of tirofiban up to 5 mg/kg/day (about 5 times the maximum recommended daily human dose when compared on a body surface area basis).

Animal studies have failed to reveal evidence of fetal harm. There are no controlled data in human pregnancy. AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

AU and UK: Use is recommended only if clearly needed and the benefit outweighs the risk. US: The manufacturer makes no recommendation regarding use during pregnancy. AU TGA pregnancy category: B1 US FDA pregnancy category: B

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Yes Comments: The effects in the nursing infant are unknown.