Critical Care Trauma Centre

ARGATROBAN

 

Name: ARGATROBAN
Classification:
  • selective thrombin inhibitor
    • reversibly inhibits the catalytic site of thrombin resulting in competitive inhibition of the enzyme and related biological activities
    • lacks antifibrinolytic activity; has no significant inhibitory effect on biosynthesis of vitamin K-dependent coagulant proteins
    • does not interact with heparin-induced antibodies
  • restricted to use by Hematology for heparin induced thrombocytopenia-thombosis syndrome
Dose:

Initial dose (by continuous infusion):

  • 0.5 mcg/kg/min
  • titrate to a PTT 1.5-3 times baseline (PTT should not exceed 100 seconds)
  • therapeutic levels usually achieved within 2.5 hours of starting therapy
  • dose should not exceed 10 mcg/kg/min

Moderate to severe hepatic dysfunction:

  • initial dose of 0.5 mcg/kg/min; may have prolonged anticoagulation due to impaired elimination

Onset of action 30 minutes, peak reponse within 2-3 hours, half life 30-50 minutes

Administration:

IV Infusion:
250 mg in 250 ml dextrose 5%, sodium chloride 0.9% or Ringer's Lactate

  • protect from light during storage and administration.
  • slight haziness may appear upon preparation, but should rapidly disappear upon mixing.
  • should be administered through a dedicated line.  
Adverse Effects:
  • bleeding
  • diarrhea, nausea/vomiting
  • elevation of serum transaminases
  • ventricular tachycardia, hypotension
Caution:

Use with caution in patients concomitantly receiving other anticoagulants or antiplatelet agents, or at increased risk of hemorrhage (eg. post major surgery or procedure, HTN)

No known reversal agent available; if required, discontinue infusion and coagulation parameters should return to baseline within 2-4 hours.

CONVERSION TO WARFARIN THERAPY:
Do not give loading dose of warfarin; initiate therapy with expected daily dose of warfarin.

Agratroban dose up to 2 mcg/kg/min: discontinue argatroban infusion when INR >4.  Repeat INR measurement in 4 to 6 hours. If repeat INR is below the desired therapeutic range, resume argatroban infusion at previous rate and repeat the procedure daily until the desired therapeutic range on warfarin alone is reached.

Agratroban dose greater than 2 mcg/kg/min: once INR>4, reduce argatroban infusion to 2 mcg/kg/min.  Repeat the INR 4 to 6 hours after reduction of the argatroban dose and follow the process outlined above for administering argatroban at doses up to 2 mcg/kg/minutge  

Drug Interactions:
  • argatroban + warfarin  = increased INR greater than seen with warfarin alone
Monitoring Therapy:
  • PTT (dose is titrated to achieve PTT 1.5 - 3 times normal)
  • INR, hemoglobin, platelet count
  • bleeding (neurological assessment, gastrointestinal assessment, puncture site inspection)
  • blood pressure
  • hepatic enzymes

Patients with HIT undergoing percutaneous coronary intervention (PCI):

See Parenteral Drug Administration Manual

Adult Critical Care Protocol:
  • May be given by IV infusion by a nurse in Adult Critical Care.
  • Continuous infusions must be administered by infusion device and the pump library must be enabled.


Lynne Kelly, Pharmacist, CCTC
Brenda Morgan, Clinical Nurse Specialist, CCTC
Last Update: September 19, 2018