Argatroban

CLINICAL USE

Anticoagulant:

  • Prophylaxis or treatment of thrombosisin patients with heparin-induced
    thrombocytopenia (HIT)
  • Adjunct in patients at risk of HITundergoing percutaneous coronary
    intervention

    DOSE IN NORMAL RENAL FUNCTION

  • Anticoagulant for prophylaxis ortreatment of thrombosis: infusion of
    2 mcg/kg/min; adjust according to
    response (APTT); maximum
    10 mcg/kg/min
  • Anticoagulant for patients undergoingpercutaneous 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                           :
    508.6
  • %Protein binding                           :
    54
  • %Excreted unchanged in urine     :
    16
  • Volume of distribution (L/kg)       :
    0.17
  • half-life – normal/ESRD (hrs)      :
    39–51 minutes/
    Unchanged

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

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

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Heparin: avoid concomitantadministration
  • Urokinase: may increase the risk ofbleeding
  • Thrombolytics: may increase risk ofbleeding complications; enhance effect of
    argatroban
  • Antiplatelets and anticoagulants: increasedrisk 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 to96 hours if refrigerated or at controlled
    room temperature and protected from
    light
  • Dilute to 1 mg/mL with sodium chloride0.9%, 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 haemodialysisanticoagulation: 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/minwas suggested, dosing being adjusted to
    maintain an APTT 1.5–2 times normal.
  • 20% of argatroban is removed during a4 hour dialysis session
  • There is no specific antidote
  • Contraindicated in patients with overtmajor bleeding
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