Preparation: Argatroban should be diluted in 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection to a final concentration of 1 mg/mL. The contents of each 2.5 mL vial should be diluted 100-fold by mixing with 250 mL of diluent. Use 250 mg (2.5 mL) per 250 mL of diluent or 500 mg (5 mL) per 500 mL of diluent. The constituted solution must be mixed by repeated inversion of the diluent bag for one minute. Upon preparation, the solution may show slight but brief haziness due to the formation of microprecipitates that rapidly dissolve upon mixing.

Initial Dosage: Before administering Argatroban, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of Argatroban for adult patients without hepatic impairment is 2 µg/kg/min, administered as a continuous infusion .

Actions: Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. It is capable of inhibiting the action of both free and clot-associated thrombin. No dosage adjustment is necessary in patients with renal dysfunction. 

Indications: as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is indicated as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (PCI). Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing Argatroban or by decreasing the infusion dosage. In clinical studies at therapeutic levels, anticoagulation parameters generally return to baseline within 2 to 4 hours after discontinuation of the drug. Reversal of anticoagulant effect may take longer in patients with hepatic impairment. 

Monitoring therapy: Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within 1-3 hours following initiation of Argatroban. Dose adjustment may be required to attain the target aPTT. Check the aPTT 2 hours after initiation of therapy to confirm that the patient has attained the desired therapeutic range. 

Dosage adjustment: After the initial dose of Argatroban, the dose can be adjusted as clinically indicated (not to exceed 10 µg/kg/min), until the steady-state aPTT is 1.5 to 3 times the initial baseline value (not to exceed 100 seconds). For patients with moderate hepatic impairment, an initial dose of 0.5 µg/kg/min is recommended, based on the approximate 4-fold decrease in Argatroban clearance relative to those with normal hepatic function. The aPTT should be monitored closely and the dosage should be adjusted as clinically indicated