Argatroban

Pronunciation

Pronunciation: ar-GAT-roe-ban
Class: Thrombin inhibitor

Trade Names

Argatroban
- Injection, solution 100 mg/mL

Pharmacology

Binds reversibly to thrombin active site, exerting its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation.

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Pharmacokinetics

Distribution

Distributes mainly in the extracellular fluid. Vd is 174 mL/kg. Approximately 54% is protein bound (20% to albumin and 34% to alpha-1 acid glycoprotein).

Metabolism

Hydroxylation and aromatization in the liver. CYP3A4/5 plays a minor role.

Elimination

Cl is approximately 5.1 mL/kg/min; terminal elimination half-life is 39 to 51 min. Approximately 65% is excreted in the feces (through biliary secretion) and approximately 22% is excreted in the urine. At least 14% is recovered in the feces as unchanged drug and 16% in the urine.

Onset

Immediate.

Peak

1 to 3 h (steady state).

Special Populations

Renal Function Impairment

No dosage adjustment is needed.

Hepatic Function Impairment

Cl is reduced and half-life is increased. Dosage adjustment is recommended.

Children

Cl is decreased in seriously ill children.

Indications and Usage

As an anticoagulant for prophylaxis and treatment of thrombosis in heparin-induced thrombocytopenia; as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention.

Contraindications

Overt major bleeding; hypersensitivity to this product or any component of this product.

Dosage and Administration

Heparin-Induced Thrombocytopenia or Heparin-Induced Thrombocytopenia and Thrombosis Syndrome
Adults

IV Initial dose is 2 mcg/kg/min as a continuous infusion; after initial dose, the dose can be adjusted as clinically indicated (not exceeding 10 mcg/kg/min) until steady-state aPTT is 1.5 to 3 times the initial baseline value (not to exceed 100 sec).

Percutaneous Coronary Intervention in Heparin-Induced Thrombocytopenia or Heparin-Induced Thrombocytopenia and Thrombosis Syndrome
Adults

IV Initial dose is 25 mcg/kg/min and bolus of 350 mcg/kg via large-bore IV line administered over 3 to 5 min. Check activated clotting time 5 to 10 min after bolus is completed. Proceed if activated clotting time is more than 300 sec. If activated clotting time is less than 300 sec, administer an additional IV bolus dose of 150 mcg/kg, increase the infusion dose to 30 mcg/kg/min, and check the activated clotting time 5 to 10 min later. If activated clotting time is more than 450 sec, decrease the infusion rate to 15 mcg/kg/min and check activated clotting time 5 to 10 min later. Once activated clotting time is between 300 and 450 sec, continue infusion dose for the duration of the procedure. In case of dissection, impending abrupt closure, thrombus formation during the procedure, or inability to achieve or maintain an activated clotting time over 300 sec, additional bolus doses of 150 mcg/kg may be administered and the infusion dose increased to 40 mcg/kg/min. Check the activated clotting time after each additional bolus or change in rate of infusion.

Coadministration of Warfarin
Adults (receiving argatroban up to 2 mcg/kg/min)

Measure INR daily during coadministration of argatroban and warfarin. In general, doses of argatroban up to 2 mcg/kg/min can be discontinued when the INR is more than 4. Repeat INR 4 to 6 h after stopping argatroban and, if the INR is below desired therapeutic range, resume argatroban infusion and repeat the procedure daily until desired therapeutic range on warfarin alone is achieved.

Adults (receiving argatroban at doses greater than 2 mcg/kg/min)

Temporarily reduce dose of argatroban to 2 mcg/kg/min and repeat the INR on argatroban and warfarin 4 to 6 h after reducing the argatroban dose; follow the process previously described for administering warfarin and argatroban at doses of up to 2 mcg/kg/min.

Hepatic Function Impairment
Adults

IV In patients with moderate hepatic function impairment, the initial dose is 0.5 mcg/kg/min; monitor aPTT closely and adjust dose as clinically indicated. In hepatic impairment in heparin-induced thrombocytopenia or heparin-induced thrombocytopenia and thrombosis syndrome patients undergoing percutaneous coronary interception, carefully titrate dose until desired level of anticoagulation is achieved.

General Advice

  • Follow manufacturer's guidelines for diluting concentrated solution in sodium chloride 0.9% injection, dextrose 5% injection, or Ringer's lactate injection before infusing.
  • Do not mix with other injections or infusions.
  • Do not administer if particulate matter or discoloration noted.

Storage/Stability

Store vials at controlled room temperature (59° to 86°F). Diluted solutions may be stored at 59° to 86°F in ambient indoor light for 24 h. When protected from light (eg, foil wrap), solutions may be stored at 68° to 77°F or refrigerated at 36° to 46°F for 96 h. Do not freeze or expose to direct sunlight.

Drug Interactions

Anticoagulants, antiplatelet agents, thrombolytics

May increase risk of bleeding.

Heparin

Allow sufficient time for effects of heparin on aPTT to decrease before starting argatroban therapy.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (11%); cardiac arrest (6%); bradycardia, ventricular tachycardia (5%); MI (4%); atrial fibrillation (3%); angina pectoris, cerebrovascular disorder, coronary occlusion, coronary thrombosis, minor hemorrhage at coronary artery bypass graft, myocardial ischemia (2%); aortic stenosis, arterial thrombosis, cerebrovascular disorder, vascular disorder (1%).

CNS

Headache (5%); intracranial hemorrhage (4%).

Dermatologic

Allergic skin reactions, including bullous eruption and rash (less than 10% to 1%).

GI

Minor hemorrhagic GI bleeding (14%); nausea (7%); diarrhea, vomiting (6%); abdominal pain (4%); major hemorrhagic GI bleeding (2%); gastroesophageal reflux disease (1%).

Genitourinary

Minor GU hemorrhage and hematuria (12%); UTI (5%); abnormal renal function (3%); major GU hemorrhage and hematuria (1%).

Hematologic

Minor decrease in hemoglobin and hematocrit (10%); sepsis (6%); overall bleeding (hemorrhagic) (5%); major decrease in hemoglobin and hematocrit, retroperitoneal hemorrhage (1%).

Respiratory

Allergic airway reactions, including coughing and dyspnea (10% or more); dyspnea (8%); coughing, hemoptysis, pneumonia (3%); lung edema (1%).

Miscellaneous

Chest pain (15%); back pain (8%); fever (7%); minor hemorrhagic event/groin, pain (5%); infection (4%); minor hemorrhagic event/brachial (2%); general allergic reactions (less than 10% to 1%).

Precautions

Monitor

In clinical trial in percutaneous coronary intervention, the activated clotting time was used for monitoring argatroban anticoagulant activity during the procedure.


Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Efficacy not affected by age in adults.

Hepatic Function

Use with caution.

Hemorrhage

Because hemorrhage can occur at any site in patients receiving argatroban, use with extreme caution in disease states or circumstances in which there is an increased danger of hemorrhage (eg, major surgery, severe hypertension, spinal anesthesia).

Parenteral anticoagulants

Ensure all parenteral anticoagulants have been discontinued before administering argatroban.

Overdosage

Symptoms

Excessive anticoagulation.

Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a hospital setting.
  • Instruct patient, family, or caregiver to report any of the following immediately: bleeding or unusual bruising, coughing, difficulty breathing, skin rash or reaction.

Copyright © 2009 Wolters Kluwer Health.

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