Action

Binds rapidly to site of thrombi, neutralizing conversion of fibrinogen to fibrin, activation of coagulation factors, and platelet aggregation (processes required for thrombus formation)

Availability

Injection: 100 mg/ml in 2.5-ml vials

Indications and dosages

➣ Treatment or prophylaxis of thrombosis in patients with heparin-induced thrombocytopenia

Adults: 2 mcg/kg/minute as a continuous I.V. infusion, to a maximum dosage of 10 mcg/kg/minute. Adjust dosage as needed to maintain activated partial thromboplastin time (APTT) at 1.5 to 3 times initial baseline value (not to exceed 100 seconds).

➣ Anticoagulation during percutaneous coronary intervention in patients who have or are at risk for heparin-induced thrombocytopenia

Adults: Start continuous I.V. infusion at 25 mcg/kg/minute and give loading dose of 350 mcg/kg by I.V. bolus over 3 to 5 minutes. Check activated clotting time (ACT) 5 to 10 minutes after bolus dose is given; adjust dosage until ACT is between 300 and 450 seconds. If ACT is below 300 seconds, give additional I.V. bolus dose of 150 mcg/kg; then increase infusion rate to 30 mcg/kg/minute, and check ACT after 5 to 10 minutes. If ACT exceeds 450 seconds, decrease infusion rate to 15 mcg/kg/minute, and check ACT after 5 to 10 minutes. Maintain adjusted infusion dosage once therapeutic ACT has been reached.

Dosage adjustment

• Hepatic impairment

Contraindications

• Hypersensitivity to drug

• Overt major bleeding

Precautions

Use cautiously in:

• hepatic impairment or disease, intracranial bleeding

• pregnant or breastfeeding patients

• children younger than age 18.

Administration

• Stop all parenteral anticoagulants before starting argatroban.

• Dilute in normal saline solution, dextrose 5% in water, or lactated Ringer's solution to a concentration of 1 mg/ml.

• Inject contents of 2.5-ml vial into 250-ml bag of diluent.

• Protect solution from direct sunlight.

Adverse reactions

CNS: headache

CV: hypotension, unstable angina, atrial fibrillation, cardiac arrest, ventricular tachycardia, cerebrovascular disorders

GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, GI bleeding

GU: urinary tract infection, minor GU tract bleeding and hematuria, renal dysfunction

Hematologic: groin bleeding, brachial bleeding, hypoprothrombinemia, thrombocytopenia, bleeding or hemorrhage

Respiratory: cough, dyspnea, pneumonia, hemoptysis

Skin: rash, bleeding at puncture site

Other: allergic reaction, pain, infection, fever, sepsis, anaphylaxis

Interactions

Drug-drug. Oral anticoagulants: prolonged prothrombin time, increased International Normalized Ratio, increased risk of bleeding

Thrombolytics: increased risk of intracranial bleeding

Drug-diagnostic tests. Hematocrit, hemoglobin: decreased values

Patient monitoring

See Monitor patient for signs and symptoms of anaphylaxis.

See Evaluate patient for bleeding tendency and hemorrhage.

• Assess neurologic status and vital signs frequently.

• Monitor CBC and coagulation studies, especially partial thromboplastin time.

See Check for signs and symptoms of serious arrhythmias and hypotension.

Patient teaching

See Instruct patient to immediately report allergic reaction and unusual bleeding or bruising.

• Tell patient to avoid activities that can cause injury. Advise him to use a soft toothbrush and electric razor to avoid gum and skin injury.

• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Tell patient that he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.