Trade Names:Argatroban- Injection, solution 100 mg/mL
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.
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).
Hydroxylation and aromatization in the liver. CYP3A4/5 plays a minor role.
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.
1 to 3 h (steady state).
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.
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.
Overt major bleeding; hypersensitivity to this product or any component of this product.
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 SyndromeAdults
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 WarfarinAdults (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 ImpairmentAdults
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.
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.
May increase risk of bleeding.Heparin
Allow sufficient time for effects of heparin on aPTT to decrease before starting argatroban therapy.
None well documented.
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%).
Headache (5%); intracranial hemorrhage (4%).
Allergic skin reactions, including bullous eruption and rash (less than 10% to 1%).
Minor hemorrhagic GI bleeding (14%); nausea (7%); diarrhea, vomiting (6%); abdominal pain (4%); major hemorrhagic GI bleeding (2%); gastroesophageal reflux disease (1%).
Minor GU hemorrhage and hematuria (12%); UTI (5%); abnormal renal function (3%); major GU hemorrhage and hematuria (1%).
Minor decrease in hemoglobin and hematocrit (10%); sepsis (6%); overall bleeding (hemorrhagic) (5%); major decrease in hemoglobin and hematocrit, retroperitoneal hemorrhage (1%).
Allergic airway reactions, including coughing and dyspnea (10% or more); dyspnea (8%); coughing, hemoptysis, pneumonia (3%); lung edema (1%).
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%).
In clinical trial in percutaneous coronary intervention, the activated clotting time was used for monitoring argatroban anticoagulant activity during the procedure.
Category B .
Safety and efficacy not established.
Efficacy not affected by age in adults.
Use with caution.
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).
Ensure all parenteral anticoagulants have been discontinued before administering argatroban.
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