Asprisol

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• Mara Healthcare Ltd
  

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  Asprisol | Teva Parenteral Medicines, Inc.

  

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  Each 250 mL polyolefin bag contains 250 mg of 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 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 Injection, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of Argatroban Injection 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 Injection for Patients With HITa 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

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

  
  
  
  Body Weight
  (kg)

  Starting Bolus Dose

  (350 mcg/kg)

  Starting and Maintenance Continuous Infusion Dosing

  For ACT 300 to 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

  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 Injection until the desired level of anticoagulation is achieved. Use of Argatroban Injection in PCI patients with clinically significant hepatic disease or AST/ALT levels greater than or equal to 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 coadministered. 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)].

  Coadministration of Warfarin and Argatroban Injection at Doses Up to 2 mcg/kg/min

  Measure INR daily while Argatroban Injection and warfarin are coadministered. In general, with doses of Argatroban Injection up to 2 mcg/kg/min, Argatroban Injection can be discontinued when the INR is greater than 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.

  Coadministration 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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