Argatroban

CLINICAL USE


Anticoagulant:

  • Prophylaxis or treatment of thrombosis

    in patients with heparin-induced
    thrombocytopenia (HIT)

  • Adjunct in patients at risk of HIT

    undergoing percutaneous coronary
    intervention

    DOSE IN NORMAL RENAL FUNCTION

  • Anticoagulant for prophylaxis or

    treatment of thrombosis: infusion of
    2 mcg/kg/min; adjust according to
    response (APTT); maximum
    10 mcg/kg/min

  • Anticoagulant for patients undergoing

    percutaneous coronary intervention:
    initially a bolus of 350 mcg/kg
    administered via a large bore IV line over
    3–5 minutes, followed by an infusion of
    25 mcg/kg/min. Additional IV bolus doses
    of 150 mcg/kg may be given if required and
    the infusion rate changed to
    15–40 mcg/kg/min

    PHARMACOKINETICS


  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :
    508.6
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :
    54
  • %Excreted unchanged in urine &nbsp &nbsp :
    16
  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :
    0.17
  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :
    39–51 minutes/
    Unchanged

    DOSE IN RENAL IMPAIRMENT


    GFR (mL/MIN)


  • 20 to 50 &nbsp &nbsp : Dose as in normal renal function
  • 10 to 20 &nbsp &nbsp : Dose as in normal renal function
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp :
    Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES


  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:
    Unlikely to be dialysed. Dose as in
    normal renal function

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :
    Not dialysed. Dose as in normal renal function
  • HDF/high flux &nbsp :
    Not dialysed. Dose as in normal renal function
  • CAV/VVHD &nbsp &nbsp &nbsp:
    Unlikely to be dialysed. Dose as in
    normal renal function

    IMPORTANT DRUG INTERACTIONS


    Potentially hazardous interactions with other drugs

  • Heparin: avoid concomitant

    administration

  • Urokinase: may increase the risk of

    bleeding

  • Thrombolytics: may increase risk of

    bleeding complications; enhance effect of
    argatroban

  • Antiplatelets and anticoagulants: increased

    risk of bleeding complications

    ADMINISTRATION


    Reconstition



    Route


    IV

    Rate of Administration


    Bolus: over 3–5 minutes

    Infusion: 2–25 mcg/kg/min

    Comments

  • Physically and chemically stable for up to

    96 hours if refrigerated or at controlled
    room temperature and protected from
    light

  • Dilute to 1 mg/mL with sodium chloride

    0.9%, glucose 5% or Lactated Ringer’s
    solution, i.e. 250 mg (2.5 mL) into 250 mL
    of diluent. The solution must be mixed by
    inversion for 1 minute

    OTHER INFORMATION

  • Can also be used for haemodialysis

    anticoagulation: 0.1 mg/kg bolus, followed
    by a continuous infusion of 0.1-0.2 mg/kg/
    hour, dosing being adjusted to maintain an
    APTT 1.5–3 times normal.

  • For CVVHD a dose of 0.5–1 mcg/kg/min

    was suggested, dosing being adjusted to
    maintain an APTT 1.5–2 times normal.

  • 20% of argatroban is removed during a

    4 hour dialysis session

  • There is no specific antidote
  • Contraindicated in patients with overt

    major bleeding