9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer’s Injection to a final concentration of 1 mg/mL. 1 ) Argatroban Injection 50 mg/50 mL (1 mg/mL) is ready for intravenous infusion. Dilution is not required. 1 ) Heparin-Induced Thrombocytopenia The dose for heparin-induced thrombocytopenia without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion.
2 ) Percutaneous Coronary Intervention The dose for patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention is started at 25 mcg/kg/min and a bolus of 350 mcg/kg administered via a large bore intravenous line over 3 to 5 minutes.
5 mL (100 mg/mL) must be diluted 100-fold prior to infusion. Argatroban should not be mixed with other drugs prior to dilution. Dilution is not required for Argatroban Injection 50 mg/50 mL (1 mg/mL). 9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer’s Injection to a final concentration of 1 mg/mL.
5-mL vial should be diluted 100-fold by mixing with 250 mL of diluent. 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 1 minute. Upon preparation, the solution may show slight but brief haziness due to the formation of microprecipitates that rapidly dissolve upon mixing.
Use of diluent at room temperature is recommended. Colder temperatures can slow down the rate of dissolution of precipitates. The final solution must be clear before use. 5. Solutions prepared as recommended are stable at controlled room temperature, 20º to 25ºC (68º to 77ºF) (see USP) in ambient indoor light for 24 hours; therefore, light-resistant measures such as foil protection for intravenous lines are unnecessary.
Solutions are physically and chemically stable for up to 96 hours when protected from light and stored at controlled room temperature, 20º to 25ºC (68º to 77ºF) (see USP) or at refrigerated conditions, 5º±3ºC (41º±5ºF). Prepared solutions should not be exposed to direct sunlight.
No significant potency losses have been noted following simulated delivery of the solution through intravenous tubing. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.
Argatroban Injection 50 mg/50 mL (1 mg/mL) Each 50 mL glass vial contains 50 mg argatroban (1 mg/mL); and, as supplied, is ready for intravenous infusion. Dilution is not required. Argatroban Injection is a clear, colorless to pale yellow solution.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if solution is cloudy, contains precipitates, or if the flip top cap is not intact.
Vial may be inverted for use with a medical infusion set. 2 Dosing in Patients with Heparin-Induced Thrombocytopenia Initial Dosage Before administering argatroban, discontinue heparin therapy and obtain a baseline activated partial thromboplastin time (aPTT).
The recommended initial dose of argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion (see Table 1). 5 to 3 times the initial baseline value (not to exceed 100 seconds). Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within 1 to 3 hours following initiation of Argatroban Injection.
Check the aPTT 2 hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range. 1) ]. 3 Dosing in Patients Undergoing Percutaneous Coronary Intervention Initial Dosage Initiate an infusion of Argatroban Injection at 25 mcg/kg/min and administer a bolus of 350 mcg/kg via a large bore intravenous line over 3 to 5 minutes (see Table 2).
Check an activated clotting time (ACT) 5 to 10 minutes after the bolus dose is completed. The PCI procedure may proceed if the ACT is greater than 300 seconds. Dosage Adjustment If the ACT is less than 300 seconds, an additional intravenous bolus dose of 150 mcg/kg should be administered, the infusion dose increased to 30 mcg/kg/min, and the ACT checked 5 to 10 minutes later (see Table 3).
If the ACT is greater than 450 seconds, decrease the infusion rate to 15 mcg/kg/min, and check the ACT 5 to 10 minutes later (Table 3). Continue titrating the dose until a therapeutic ACT (between 300 and 450 seconds) has been achieved; continue the same infusion rate for the duration of the PCI procedure.
In case of dissection, impending abrupt closure, thrombus formation during the procedure, or inability to achieve or maintain an ACT over 300 seconds, additional bolus doses of 150 mcg/kg may be administered and the infusion dose increased to 40 mcg/kg/min.
Check the ACT after each additional bolus or change in the rate of infusion. 2 lbs †Additional intravenous bolus dose of 150 mcg/kg should be administered if ACT less than 300 seconds. * No bolus dose is given if ACT greater than 450 seconds Monitoring Therapy For use in PCI, therapy with Argatroban Injection is monitored using ACT.
Obtain ACTs before dosing, 5 to 10 minutes after bolus dosing, following adjustments in the infusion rate, and at the end of the PCI procedure. Obtain additional ACTs every 20 to 30 minutes during prolonged procedure. 1) ] . 5 mcg/kg/min is recommended, based on the approximately 4-fold decrease in argatroban clearance relative to those with normal hepatic function.
Monitor the aPTT closely, and adjust the dosage as clinically indicated. Monitoring Therapy Achievement of steady state aPTT levels may take longer and require more dose adjustments in patients with hepatic impairment compared to patients with normal hepatic function.
For patients with hepatic impairment undergoing PCI and who have HIT or are at risk for HIT, carefully titrate argatroban until the desired level of anticoagulation is achieved. 2) ]. 5 Conversion to Oral Anticoagulant Therapy Initiating Oral Anticoagulant Therapy When converting patients from argatroban to oral anticoagulant therapy, consider the potential for combined effects on INR with co-administration of argatroban and warfarin.
A loading dose of warfarin should not be used. Initiate therapy using the expected daily dose of warfarin. To avoid prothrombotic effects and to ensure continuous anticoagulation when initiating warfarin, it is suggested that argatroban and warfarin therapy be overlapped.
There are insufficient data available to recommend the duration of the overlap. Co-Administration of Warfarin and Argatroban Injection at Doses up to 2 mcg/kg/min Measure INR daily while Argatroban Injection and warfarin are co-administered.
In general, with doses of Argatroban Injection up to 2 mcg/kg/min, Argatroban Injection can be discontinued when the INR is >4 on combined therapy. After Argatroban Injection is discontinued, repeat the INR measurement in 4 to 6 hours.
If the repeat INR is below the desired therapeutic range, resume the infusion of Argatroban Injection and repeat the procedure daily until the desired therapeutic range on warfarin alone is reached. Co-Administration of Warfarin and Argatroban Injection at Doses Greater than 2 mcg/kg/min For doses of argatroban greater than 2 mcg/kg/min, the relationship of INR between warfarin alone to the INR on warfarin plus argatroban is less predictable.
In this case, in order to predict the INR on warfarin alone, temporarily reduce the dose of Argatroban Injection to a dose of 2 mcg/kg/min. Repeat the INR on Argatroban Injection and warfarin 4 to 6 hours after reduction of the Argatroban Injection dose and follow the process outlined above for administering Argatroban Injection at doses up to 2 mcg/kg/min.