Division of Hematology & Thromboembolism

Clinical Protocols (and Reversals): Argatroban®

1 vial = 2.5 mL
Dilute in NS or D5W or Ringer’s lactate
Use 1 vial/250 mL diluent bag or 2 vials/500 mL diluent bag (final concentration 1 mg/mL)

Dosing Checklist

  • Heparin must be discontinued before administration of Argatroban.
  • A baseline aPTT should be obtained before initiating Argatroban therapy. Argatroban is not a good choice in patients with elevated baseline aPTTs and other agents should be considered in this setting.
  • The aPTT should be rechecked 2 hours after infusion initiation and the dose should be adjusted by 0.2 – 0.5 µg/kg/min until target steady-state aPTT values of 1.5 to 3.0 times baseline are attained (not to exceed 100 seconds; maximum dose 10 µg/kg/min).
  • Monitor the INR daily when converting from Argatroban to warfarin.

Recommended Dosing Regimen for HIT Patients

  If renal impairment If moderate hepatic impairment or bleeding risks
Approved initiation dose 2 µg/kg/min; however, many centres start at 1 µg/kg/min as supratherapeutic aPTTs are common with the higher dose* No dosage adjustment Initiate at 0.5 µg/kg/min
Titrate until steady-state aPTT is 1.5 - 3.0 x baseline value (consider aiming for lower end of range if no thrombosis). Total dose not to exceed 10 µg/kg/min or aPTT of 100 seconds.
*2008 ACCP guidelines also recommend 0.5 to 1.2 µg/kg/min for patients with heart failure, anasarca, multisystem failure, or post cardiac surgery.

 

Standard Starting Infusion Rates for 1 mg/mL final concentration

2.0 µg/kg/min Dose
1.0 µg/kg/min Dose
Body Weight (kg)
Infusion Rate
(mL/hr)
Body Weight (kg)
Infusion Rate
(mL/hr)
50
6
50
3
60
7
60
4
70
8
70
4
80
10
80
5
90
11
90
5
100
12
100
6
110
13
110
6
120
14
120
7
130
16
130
8
140
17
140
8

 

Conversion to Oral Anticoagulant Therapy

Initiating Oral Anticoagulant Therapy
When converting to oral contraceptive therapy, a loading dose of warfarin should not be used. Initiate therapy using the expected daily dose of warfarin.

Co-Administration of Warfarin and Argatroban at Doses up to 2 µg/kg/min
The concomitant use of Argatroban with warfarin results in prolongation of INR beyond that produced by warfarin alone. INR should be measured daily while Argatroban and warfarin are co-administered. In general, with doses of Argatroban up to 2 µg/kg/min, Argatroban can be discontinued when the INR is > 4.0. After Argatroban is discontinued, repeat the INR measurement in 4 to 6 hours. If the repeat INR is below the desired therapeutic range, resume the infusion Argatroban and repeat the procedure daily until the desired therapeutic range on warfarin alone is reached.

Co-Administration of Warfarin and Argatroban at Doses greater than 2 µg/kg/min
For doses greater than 2 µg/kg/min, the relationship between INR on warfarin alone and warfarin plus Argatroban is less predictable. In this case, in order to predict the INR on warfarin alone, temporarily reduce the dose of Argatroban to a dose of 2 µg/kg/min. Repeat the INR on Argatroban and warfarin 4 to 6 hours after Argatroban reduction and follow the process outlined above for dosing Argatroban at up to 2 µg/kg/min.

*If stopping argatroban to measure the true INR while transitioning to warfarin is not an option, Factor Xa levels can be measured and the warfarin dose adjusted to achieve a therapeutic level of less than 25%.