Aggrastat

Name: Aggrastat

Tirofiban Interactions

Avoid taking aspirin or NSAIDs (nonsteroidal anti-inflammatory drugs) without your doctor's advice. NSAIDs include ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others. Taking any of these medicines during or shortly after your treatment with tirofiban may cause you to bruise or bleed easily.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Avoid drinking alcohol while receiving tirofiban. Alcohol may increase your risk of bleeding in your stomach or intestines.

Tell your doctor about all your current medicines and any you start or stop using, especially other medications to prevent or treat blood clots such as:

  • clopidogrel, ticlopidine,
  • dalteparin, enoxaparin, tinzaparin;
  • desirudin, dabigatran, fondaparinux.
  • dipyridamole; or
  • warfarin, Coumadin, Jantoven.

This list is not complete. Other drugs may interact with tirofiban, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Overdose

In clinical trials, inadvertent overdosage with AGGRASTAT occurred in doses up to 2 times the recommended dose for initial infusion doses. Inadvertent overdosage occurred in doses up to 9.8 times the 0.15 mcg/kg/min maintenance infusion rate.

The most frequently reported manifestation of overdosage was bleeding, primarily minor mucocutaneous bleeding events and minor bleeding at the sites of cardiac catheterization [see WARNINGS AND PRECAUTIONS].

Overdosage of AGGRASTAT should be treated by assessment of the patient's clinical condition and cessation or adjustment of the drug infusion as appropriate.

AGGRASTAT can be removed by hemodialysis.

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Interactions for Aggrastat

Specific Drugs

Drug

Interaction

Comments

Anticoagulants, oral

Potential increased risk of bleeding1

Use with caution1 20 21 91

Clopidogrel

Potential increased risk of bleeding1 4 22

Use with caution1 20 21 91

Dextran

Increased risk of bleeding1

Some clinicians recommend against concomitant use91

Dipyridamole

Potential increased risk of bleeding1

Use with caution1 20 21 91

GP IIb/IIIa-receptor inhibitors (abciximab, eptifibatide)

Possible additive pharmacologic effects1 4

Concomitant use contraindicated1

Heparin

Increased risk of bleeding; 1 5 6 11 14 possible additive effects on ACT56

Monitor aPTT or ACT during therapy;1 5 6 11 37 44 consider dosage adjustment of heparin56

Levothyroxine

Possible increased tirofiban clearance 1

Clinical importance not known1

NSAIAs

Potential increased risk of bleeding1

Use with caution1 20 21 91

Omeprazole

Possible increased tirofiban clearance 1

Clinical importance not known1

Thrombolytics

Increased risk of bleeding1

Use concomitantly with caution; no concomitant use studies to date20 21 91

Ticlopidine

Potential increased risk of bleeding1 4 22

Use with caution1 20 21 91

Aggrastat Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common
  • Abdominal or stomach pain or swelling
  • arm, back, or jaw pain
  • black, tarry stools
  • blood in the eyes
  • blood in the urine
  • bruising or purple areas on the skin
  • chest pain or discomfort
  • chest tightness or heaviness
  • coughing up blood
  • decreased alertness
  • fast or irregular heartbeat
  • headache
  • joint pain or swelling
  • nausea
  • nosebleeds
Less common
  • Bleeding gums
  • lightheadedness or fainting
  • pinpoint red spots on the skin
  • severe, unusual tiredness or weakness
  • slow heartbeat
  • swelling of the hands, ankles, feet, or lower legs
Incidence not known
  • Chills or fever
  • cough
  • difficulty swallowing
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • skin rash, hives, or itching
  • trouble breathing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Pain in the legs or hips
Less common
  • Dizziness
  • sweating

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

What do I need to tell my doctor BEFORE I take Aggrastat?

  • If you have an allergy to tirofiban or any other part of Aggrastat (tirofiban).
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have active bleeding or you are at risk for very bad bleeding.
  • If you have had bleeding problems, an injury, or surgery in the last month.
  • If you have ever had a low platelet count during past use of this medicine or another drug like this one.
  • If you are breast-feeding. Do not breast-feed while you take Aggrastat.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Aggrastat with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

How do I store and/or throw out Aggrastat?

  • If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Drug Interactions

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

Use in specific populations

Pregnancy

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. Tirofiban has been shown to cross the placenta in pregnant rats and rabbits. Studies with tirofiban HCl at intravenous doses up to 5 mg/kg/day (about 5 and 13 times the maximum recommended daily human dose for rat and rabbit, respectively, when compared on a body surface area basis) have revealed no harm to the fetus.

Nursing Mothers

It is not known whether tirofiban is excreted in human milk. However, significant levels of tirofiban were shown to be present in rat milk. Because many drugs are excreted in human milk, and because of the potential for adverse effects on the nursing infant, discontinue nursing or discontinue Aggrastat.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the total number of patients in controlled clinical studies of Aggrastat, 43% were 65 years and over, while 12% were 75 and over. With respect to efficacy, the effect of Aggrastat in the elderly (≥65 years) appeared similar to that seen in younger patients (<65 years). Elderly patients receiving Aggrastat with heparin or heparin alone had a higher incidence of bleeding complications than did younger patients, but the incremental risk of bleeding in patients treated with Aggrastat in combination with heparin compared to the risk in patients treated with heparin alone was similar regardless of age. No dose adjustment is recommended for the elderly population [see Dosage and Administration (2)].

Renal Insufficiency

Patients with moderate to severe renal insufficiency have decreased plasma clearance of Aggrastat. Reduce the dosage of Aggrastat in patients with severe renal insufficiency [see Dosage and Administration (2) and Clinical Pharmacology (12.3)].

Safety and efficacy of Aggrastat has not been established in patients on hemodialysis.

Aggrastat - Clinical Pharmacology

Mechanism of Action

Aggrastat is a reversible antagonist of fibrinogen binding to the GP IIb/IIIa receptor, the major platelet surface receptor involved in platelet aggregation. When administered intravenously, Aggrastat inhibits ex vivo platelet aggregation in a dose- and concentration-dependent manner.

When given according to the PRISM-PLUS regimen of 0.4 mcg/kg/min over 30 minutes followed by a 0.1 mcg/kg/min maintenance infusion, >90% inhibition of platelet aggregation is attained by the end of the 30-minute infusion. When given according to the recommended regimen of 25 mcg/kg followed by a 0.15 mcg/kg/min maintenance infusion, >90% inhibition of platelet aggregation is attained within 10 minutes. Platelet aggregation inhibition is reversible following cessation of the infusion of Aggrastat.

Pharmacodynamics

Aggrastat inhibits platelet function, as demonstrated by its ability to inhibit ex vivo adenosine phosphate (ADP)-induced platelet aggregation and prolong bleeding time in healthy subjects and patients with coronary artery disease. The time course of inhibition parallels the plasma concentration profile of the drug.

Following discontinuation of an infusion of Aggrastat 0.10 mcg/kg/min, ex vivo platelet aggregation returns to near baseline in 4 to 8 hours in approximately 90% of patients with coronary artery disease. The addition of heparin to this regimen does not significantly alter the percentage of subjects with >70% inhibition of platelet aggregation (IPA), but does increase the average bleeding time, as well as the number of patients with bleeding times prolonged to >30 minutes. Similar platelet aggregation recovery rates are observed following discontinuation of a 0.15 mcg/kg/min infusion.

Pharmacokinetics

Tirofiban has a half-life of approximately 2 hours. It is cleared from the plasma largely by renal excretion, with about 65% of an administered dose appearing in urine and about 25% in feces, both largely as unchanged tirofiban. Metabolism appears to be limited.

Tirofiban is not highly bound to plasma proteins and protein binding is concentration independent over the range of 0.01 to 25 mcg/mL. The unbound fraction in human plasma is 35%. The steady state volume of distribution of tirofiban ranges from 22 to 42 liters.

In healthy subjects, the plasma clearance of tirofiban ranges from 213 to 314 mL/min. Renal clearance accounts for 39 to 69% of plasma clearance.

Specific Populations

There is no effect on clearance of tirofiban by sex, race, age, or hepatic impairment.

Renal Insufficiency

Plasma clearance of tirofiban is decreased about 40% in subjects with creatinine clearance <60 mL/min and >50% in patients with creatinine clearance <30 mL/min, including patients requiring hemodialysis [see Dosage and Administration (2.3)]. Tirofiban is removed by hemodialysis.

Breastfeeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

For the Consumer

Applies to tirofiban: intravenous solution

Along with its needed effects, tirofiban (the active ingredient contained in Aggrastat) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking tirofiban:

More common
  • Abdominal or stomach pain or swelling
  • arm, back, or jaw pain
  • black, tarry stools
  • blood in the eyes
  • blood in the urine
  • bruising or purple areas on the skin
  • chest pain or discomfort
  • chest tightness or heaviness
  • coughing up blood
  • decreased alertness
  • fast or irregular heartbeat
  • headache
  • joint pain or swelling
  • nausea
  • nosebleeds
Less common
  • Bleeding gums
  • lightheadedness or fainting
  • pinpoint red spots on the skin
  • severe, unusual tiredness or weakness
  • slow heartbeat
  • swelling of the hands, ankles, feet, or lower legs
Incidence not known
  • Chills or fever
  • cough
  • difficulty swallowing
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • skin rash, hives, or itching
  • trouble breathing

Some side effects of tirofiban may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Pain in the legs or hips
Less common
  • Dizziness
  • sweating

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