aggrastat

tirofiban hydrochloride

Aggrastat

Pharmacologic class: Glycoprotein (GP IIb/IIIa)-receptor inhibitor

Therapeutic class: Platelet aggregation inhibitor

Pregnancy risk category B

Action

Inhibits reversible platelet aggregation by binding to GP IIb/IIIa receptor on platelets

Availability

Injection: 25-ml and 50-ml vials (250 mcg/ml), 100-ml and 250-ml premixed vials (50 mcg/ml)

Indications and dosages

➣ Acute coronary syndrome (given with heparin); patients undergoing percutaneous transluminal coronary angioplasty (PTCA) or atherectomy

Adults: Loading dose of 0.4 mcg/kg/minute I.V. for 30 minutes, followed by continuous I.V. infusion of 0.1 mcg/kg/minute for 48 to 108 hours in patients being managed medically. Continue infusion for 12 to 24 hours after PTCA or atherectomy.

Dosage adjustment

• Renal insufficiency

Contraindications

• Hypersensitivity to drug or its components

• Active internal bleeding or history of bleeding diathesis within past 30 days

• Cerebrovascular accident (CVA) within past 30 days, or history of hemorrhagic CVA

• History of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, aneurysm, or thrombocytopenia after previous tirofiban use

• History, symptoms, or findings that suggest aortic dissection

• Severe hypertension

• Acute pericarditis

• Major surgery or severe trauma within past 30 days

• Concurrent use of other parenteral GP IIb/IIIa inhibitors

Precautions

Use cautiously in:

• renal disease

• elderly patients

• pregnant or breastfeeding patients

• children younger than age 18 (safety not established).

Administration

Know that drug comes both in premixed vials of 50 mcg/ml and injection concentrate of 250 mcg/ml.

• Dilute injection concentrate to same concentration as premixed vial (50 mcg/ml) by withdrawing and discarding 50 ml of solution from 250-ml plastic bag of normal saline solution or dextrose 5% in water, or by withdrawing and discarding 100 ml of solution from 500-ml plastic bag of same solution and replacing with equal volume of concentrated drug form.

• Mix I.V. solution well and inspect visually before administering.

• Squeeze plastic bag and check for leaks; discard if it has leaks.

• Don't use drug in series connections with other plastic bags. Don't add other drugs to bag containing tirofiban.

Adverse reactions

CNS: headache, dizziness, spinal-epidural hematoma, intracranial hemorrhage

CV: vasovagal reaction, bradycardia, hemopericardium, coronary artery dissection

GI: nausea, vomiting, occult bleeding, hematemesis, retroperitoneal hemorrhage

GU: pelvic pain, hematuria

Hematologic: bleeding, thrombocytopenia

Musculoskeletal: leg pain

Respiratory: pulmonary hemorrhage

Skin: diaphoresis

Other: infusion site bleeding, chills, fever, edema, allergic reactions, anaphylaxis

Interactions

Drug-drug. Clopidogrel, dipyridamole, nonsteroidal anti-inflammatory drugs, oral anticoagulants (such as thrombolytics, ticlopidine, warfarin), other drugs affecting hemostasis: increased risk of bleeding

Levothyroxine, omeprazole: increased renal clearance of tirofiban

Vitamin A: increased risk of bleeding

Drug-diagnostic tests. Hematocrit, hemoglobin, platelets: decreased values

Drug-herbs. Alfalfa, anise, arnica, astragalus, bilberry, black currant seed oil, bladderwrack, bogbean, boldo (with fenugreek), borage oil, buchu, capsaicin, cat's claw, celery, chaparral, chincona bark, clove oil, dandelion, dong quai, evening primrose oil, fenugreek, feverfew, garlic, ginger, ginkgo, guggul, papaya extract, red clover, rhubarb, safflower oil, skullcap, tan-shen: increased risk of bleeding

Patient monitoring

Monitor CBC, platelet count, and coagulation studies. Assess stool for occult blood.

• Watch for bleeding at puncture sites, especially at cardiac catheterization access site. Immobilize access site to reduce bleeding risk.

Monitor for signs and symptoms of bleeding in cranium and other body systems (especially respiratory, GI, and GU).

• Monitor vital signs and ECG.

Assess cardiovascular status. Stay alert for signs and symptoms of coronary artery dissection or hemopericardium.

Patient teaching

Teach patient to recognize and immediately report serious adverse reactions.

• Tell patient he will be closely monitored and undergo regular blood testing during therapy.

tirofiban

(tye-roe-fye-ban) tirofiban,

Aggrastat

(trade name)

Classification

Therapeutic: antiplatelet agents
Pharmacologic: glycoprotein iib iiia inhibitors
Pregnancy Category: B

Indications

Treatment of acute coronary syndrome (unstable angina/non–Q-wave MI), including patients who will be managed medically and those who will undergo percutaneous transluminal angioplasty (PCTA) or atherectomy.Used concurrently with aspirin and heparin.

Action

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

Therapeutic effects

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

Contraindications/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; Lactation: Lactation.Use Cautiously in: Platelet count <150,000/mm3;Hemorrhagic retinopathy;Female patients (↑ risk of bleeding);Severe renal insufficiency (↓ rate of infusion by 50% if CCr <30 mL/min); Obstetric / Pediatric: Safety not established; use in pregnancy only if clearly needed; Geriatric: ↑ risk of bleeding.

Adverse Reactions/Side Effects

Noted for patients receiving heparin and aspirin in addition to tirofiban

Central nervous system

  • dizziness
  • headache (most frequent)

Cardiovascular

  • bradycardia
  • coronary dissection
  • edema
  • vasovagal reaction

Gastrointestinal

  • nausea

Dermatologic

  • hives
  • rash

Hematologic

  • bleeding
  • thrombocytopenia

Musculoskeletal

  • leg pain

Miscellaneous

  • fever
  • hypersensitivity reactions
  • pelvic pain
  • sweating

Interactions

Drug-Drug interaction

Concurrent use of aspirin, NSAIDs, warfarin, heparin, heparin-like agents, abciximab, eptifibatide, clopidogrel, ticlopidine, or dipyridamole may ↑ risk of bleeding, although these agents are frequently used together or in sequence.Risk of bleeding may be ↑ by concurrent use of cefotetan, cefoperazone, or valproic acid.↑ anticoagulant effect and bleeding risk with anise, arnica, chamomile, clove, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, Panax ginseng, licorice, and others.

Route/Dosage

Intravenous (Adults) 0.4 mcg/kg/min for 30 min, then 0.1 mcg/kg/min, continued throughout angiography and for 12–24 hr after angioplasty or atherectomy.

Renal Impairment

Intravenous (Adults) CCr <30 mL/min—0.2 mcg/kg/min for 30 min, then 0.05 mcg/kg/min, continued throughout angiography and for 12–24 hr after angioplasty or atherectomy.

Availability

Premixed solution for infusion: 5 mg/100 mL (50 mcg/mL) in 100-mL single-dose containers, 12.5 mg/250 mL (50 mcg/mL) in 250-mL single-dose containers

Nursing implications

Nursing 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.

Potential Nursing Diagnoses

Ineffective tissue perfusion (Indications)

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.
  • Intravenous Administration
  • pH: 5.5–6.5.
  • 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: acyclovir, alfentanil, allopruinol, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, ampicillin, ampicillin/sulbactam, anidulafungin, argatroban, arsenic trioxide, atracurium, atropine, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, busulfan, butorphanol, calcium chloride, calcium gluconate, capreomycin, carboplatin, carmustine, caspofungin, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doxacurium, doxorubicin, doxorubicin liposome, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, epirubicin, eptifibatide, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydralazine, hydrocortisone, hydromorphone, idarubicin, ifosfamide, imipenem/cilastatin, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, mesna, methylhexital, methotrexate, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitomycin, mitoxantrone, morphine, moxifloxacin, mycophenolate, nafcillin, nalbuphine, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, pantoprazole, pemetrexed, pentobarbital, phenobarbital, phentolamine, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, streptozocin, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tobramycin, topotecan, vancomycin, vasopressin, vecuronium, verapanil, vinblastine, vincristine, vinorelbine, voriconazole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: amphotericin B colloidal, amphotericin B lipid complex, dantrolene, diazepam, phenytoin

Patient/Family Teaching

  • Inform patient of the purpose of tirofiban.
  • Instruct patient to notify health care professional immediately if any bleeding is noted.

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.

aggrastat

An anticoagulant drug used for the prevention of heart attacks in patients with unstable ANGINA PECTORIS. A brand name is Tirofiban. See SAW-SCALED VIPER VENOM.