Ambisome

CLINICAL USE

Antifungal agent:
Systemic fungal infections (yeasts and

yeast-like fungi including Candida
albicans)
Treatment of visceral leishmaniasis

DOSE IN NORMAL RENAL FUNCTION

1–3 mg/kg/day, maximum 5 mg/kg
(unlicensed dose)
Visceral leishmaniasis: total dose of
21–30 mg/kg given over 10–21 days

PHARMACOKINETICS

  • Molecular weight                           :
    924.1
  • %Protein binding                           :
    90
  • %Excreted unchanged in urine     :
    2–5
  • Volume of distribution (L/kg)       :
    0.1–0.44
  • half-life – normal/ESRD (hrs)      :
    6.3–10.7/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 with

    aminoglycosides and other nephrotoxic
    agents and cytotoxics
    Cardiac glycosides: increased toxicity if

    hypokalaemia occurs
    Corticosteroids: increased risk of

    hypokalaemia (avoid concomitant use
    unless corticosteroids are required to
    control reactions)
    Flucytosine: enhanced toxicity in

    combination with amphotericin

    ADMINISTRATION

    Reconstition

    See SPC. Prepare intermittent infusion

    in glucose 5% (incompatible with sodium
    chloride 0.9%, electrolytes or other drugs).
    Reconstitute vial contents with water for
    injection
    Dilute to a concentration of 0.2–2 mg/mL

    Route

    IV infusion

    Rate of Administration

    30–60 minutes

    Comments

    Paracetamol and parenteral pethidine

    may alleviate rigors associated
    with amphotericin administration.
    Antihistamines can also be administered
    to control reactions
    Flush existing IV line with glucose 5%

    before and after infusion administration
    For patients on CAV/VVHD, amphotericin

    should 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 act

    synergistically when co-administered
    enabling lower doses to be used effectively
    A test dose of amphotericin is

    recommended at the beginning of a new
    course (1 mg over 10 minutes then stop
    and observe for next 30 minutes)
    Monitor renal function, full blood count,

    potassium, magnesium and calcium levels
    Liposomal amphotericin is considerably

    less nephrotoxic compared with
    amphotericin, but is considerably more
    expensive

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