Amphotericin

CLINICAL USE

Antifungal agent:

  • Systemic fungal infections (yeasts andyeast-like fungi including Candida
    albicans

    DOSE IN NORMAL RENAL FUNCTION

    5 mg/kg/day for at least 14 days (see
    individual product data sheet)

    PHARMACOKINETICS

  • Molecular weight                           :
    924.1
  • %Protein binding                           :
    90
  • %Excreted unchanged in urine     :
    <1
  • Volume of distribution (L/kg)       :
    2286
  • half-life – normal/ESRD (hrs)      :
    173.4/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                :
    Not dialysed. Dose as in normal renal function
  • HD                     :
    Not dialysed. Dose as in normal renal function
  • HDF/high flux   :
    Unknown dialysability. Dose as in
    normal renal function
  • CAV/VVHD      :
    Not dialysed. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs

  • Ciclosporin: increased nephrotoxicity
  • Tacrolimus: increased nephrotoxicity
  • Increased risk of nephrotoxicity withaminoglycosides and other nephrotoxic
    agents and cytotoxics
  • Cardiac glycosides: increased toxicity ifhypokalaemia occurs
  • Corticosteroids: increased risk ofhypokalaemia (avoid concomitant use
    unless corticosteroids are required to
    control reactions)
  • Flucytosine: enhanced toxicity incombination with amphotericin

    ADMINISTRATION

    Reconstition

    See individual data sheet. Prepare

    intermittent infusion in glucose 5%
    (incompatible with sodium chloride 0.9%,
    electrolytes or other drugs).

  • Dilute to a concentration of 1–2 mg/mL

    Route

    IV infusion

    Rate of Administration

    2.5 mg/kg/hour

    Comments

  • Paracetamol and parenteral pethidinemay alleviate rigors associated with
    amphotericin administration. Can also use
    antihistamines to control reactions
  • Flush existing IV line with glucose 5%before and after infusion administration
  • For patients on CAV/VVHD, amphotericinshould be given into the venous return of
    the dialysis circuit
    Should be given post dialysis

    OTHER INFORMATION

    *** AMPHOTERICIN IS HIGHLY
    NEPHROTOXIC ***

  • Can cause distal tubular acidosis
  • May cause polyurea, hypovolaemia,hypokalaemia and acidosis.
  • Amphotericin and flucytosine actsynergistically when co-administered
    enabling lower doses to be used effectively
  • A test dose of amphotericin isrecommended at the beginning of a new
    course (1 mg over 15 minutes)
  • Monitor renal function, full blood count,potassium, magnesium and calcium levels
  • Liposomal amphotericin is considerablyless nephrotoxic compared with
    conventional amphotericin B, but is
    considerably more expensive
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