Argatroban Solution

Argatroban Solution Manufacturers

• Sandoz Inc
  

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  Argatroban Solution | Sandoz Inc

  

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  Each 125 mL glass vial contains 125 mg of argatroban (1mg/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 the solution is cloudy, contains precipitates, or if the flip-off seal is not intact.

  2.1 Dosing in Patients With Heparin-Induced Thrombocytopenia 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 mcg/kg/min, administered as a continuous infusion (see Table 1).

  Table 1.

  Recommended Doses and Infusion Rates for 2 mcg/kg/min Dose of Argatroban for Patients

  With HIT* and Without Hepatic Impairment (1 mg/mL Concentration)

  Body Weight

  (kg)

  Dose

  (mcg/min)

  Infusion Rate

  (mL/hr) 50 100 6 60 120 7 70 140 8 80 160 10 90 180 11 100 200 12 110 220 13 120 240 14 130 260 16 140 280 17

  * with or without thrombosis

  Monitoring Therapy:

  For use in HIT, therapy with Argatroban Injection is monitored using the aPTT with a target range of 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.

  Dosage Adjustment:

  After the initiation of Argatroban Injection, adjust the dose (not to exceed 10 mcg/kg/min) as necessary to obtain a steady-state aPTT in the target range [see Clinical Studies (14.1)].

  2.2 Dosing in Patients Undergoing Percutaneous Coronary Interventions 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 2).

  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.

  Table 2.

  Recommended Starting and Maintenance Doses (Within the Target ACT Range) of Argatroban Injection in Patients Undergoing PCI Without Hepatic Impairment

  (1 mg/mL Concentration)

  Body

  Weight

  (kg)

  Starting Bolus Dose

  (350 mcg/kg)

  Starting and Maintenance

  Continuous Infusion Dosing

  For ACT 300-450 seconds

  25 mcg/kg/min

  Bolus

  Dose

  (mcg)

  Bolus

  Volume

  (mL)

  Continuous

  Infusion

  Dose

  (mg/min)

  Continuous

  Infusion

  Rate

  (mL/hr) 50 17500 18 1250 75 60 21000 21 1500 90 70 24500 25 1750 105 80 28000 28 2000 120 90 31500 32 2250 135 100 35000 35 2500 150 110 38500 39 2750 165 120 42000 42 3000 180 130 45500 46 3250 195 140 49000 49 3500 210

  NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 lbs

  Table 3.

  Recommended Dose Adjustments of Argatroban Injection for Patients Outside of ACT

  Target Range Undergoing PCI Without Hepatic Impairment (1 mg/mL Concentration)

  Body

  Weight

  (kg)

  If ACT

  Less than 300 seconds

  Dosage Adjustment†

  30 mcg/kg/min

  If ACT

  Greater than 450 seconds

  Dosage Adjustment*

  15 mcg/kg/min

  Additional

  Bolus

  Dose

  (mcg)

  Bolus

  Volume

  (mL)

  Continuous

  Infusion

  Dose

  (mcg/min)

  Continuous

  Infusion

  Rate

  (mL/hr)

  Continuous

  Infusion

  Dose

  (mcg/min)

  Continuous

  Infusion

  Rate

  (mL/hr) 50 7500 8 1500 90 750 45 60 9000 9 1800 108 900 54 70 10500 11 2100 126 1050 63 80 12000 12 2400 144 1200 72 90 13500 14 2700 162 1350 81 100 15000 15 3000 180 1500 90 110 16500 17 3300 198 1650 99 120 18000 18 3600 216 1800 108 130 19500 20 3900 234 1950 117 140 21000 21 4200 252 2100 126

  NOTE: 1 mg = 1000 mcg; 1 kg = 2.2 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 a prolonged procedure.

  Continued Anticoagulation after PCI:

  If a patient requires anticoagulation after the procedure, Argatroban Injection may be continued, but at a rate of 2 mcg/kg/min and adjusted as needed to maintain the aPTT in the desired range. [see Dosage and Administration (2.1)].

  2.3 Dosing in Patients With Hepatic Impairment

  For adult patients with HIT and moderate or severe hepatic impairment (based on Child-Pugh classification), an initial dose of 0.5 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. Use of Argatroban in PCI patients with clinically significant hepatic disease or AST/ALT levels ≥3 times the upper limit of normal should be avoided [see Warnings and Precautions (5.2)].

  2.4 Dosing in Pediatric Patients With Heparin-Induced Thrombocytopenia/ Heparin-Induced Thrombocytopenia and Thrombosis Syndrome Initial Dosage:

  Initial argatroban infusion doses are lower for seriously ill pediatric patients compared to adults with normal hepatic function [see Use in Specific Populations (8.4)].

  Monitoring Therapy:

  In general, therapy with argatroban is monitored using the aPTT. Tests of anticoagulant effects (including the aPTT) typically attain steady-state levels within one to three hours following initiation of argatroban in patients without hepatic impairment [see Warnings and Precautions (5.2)]. Dose adjustment may be required to attain the target aPTT. Check the aPTT two hours after initiation of therapy and after any dose change to confirm that the patient has attained the desired therapeutic range.

  Dosage Adjustment: [see Use in Specific Populations (8.4)] 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 International Normalized Ratio (INR). To avoid prothrombotic effects and to ensure continuous anticoagulation when initiating warfarin, overlap Argatroban Injection and warfarin therapy. There are insufficient data available to recommend the duration of the overlap. Initiate therapy using the expected daily dose of warfarin. A loading dose of warfarin should not be used.

  The relationship between INR and bleeding risk is altered when argatroban and warfarin are co-administered. The combination of argatroban and warfarin does not cause further reduction in the vitamin K–dependent factor Xa activity than that which is seen with warfarin alone. The relationship between INR obtained on combined therapy and INR obtained on warfarin alone is dependent on both the dose of argatroban and the thromboplastin reagent used. The INR value on warfarin alone (INRW) can be calculated from the INR value on combination argatroban and warfarin therapy [see Drug Interactions (7.2) and Clinical Pharmacology (12.2)].

  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 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.

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