Fungizonel

Fungizone

CLINICAL USE

Antifungal agent: Systemic fungal infections (yeasts and yeast-like fungi including Candida albicans)

DOSE IN NORMAL RENAL FUNCTION

250 micrograms – 1.5 mg/kg/day Can be given on alternate days if using a higher dose

PHARMACOKINETICS

Molecular weight : 924.1

%Protein binding : >90

%Excreted unchanged in urine : 2–5

Volume of distribution (L/kg) : 4

half-life – normal/ESRD (hrs) : 24–48 (up to 15 days with long-term use)/ 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 GFR <10 mL/min

HD : Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux : Not dialysed. Dose as in GFR <10 mL/min

CAV/VVHD : Not dialysed. Dose as in GFR=10– 20 mL/min

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. pH should be adjusted to >4.2 Dilute to a concentration of 10 mg in 100 mL

Route

IV infusion

Rate of Administration

2–6 hours If given over 12–24 hours there is a reduced incidence of side effects

Comments

Minimum volume peripherally 0.2 mg/mL, centrally 0.5 mg/mL. (UK Critical Care Group, Minimum Infusion Volumes for fluid restricted critically ill patients, 3rd Edition, 2006) Higher rates of infusion are associated with greater risk of adverse reactions. Administration over less than 1 hour, particularly in renal failure, has been associated with hyperkalaemia and arrhythmias Paracetamol and parenteral pethidine may alleviate rigors associated with amphotericin administration. Can also give antihistamines and corticosteroids 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 Amphotericin iV – Fungizone t is not licensed for use by anyone else. AMPhoTEriCin iV – FUnGiZonE 51

OTHER INFORMATION

*** AMPHOTERICIN IS HIGHLY NEPHROTOXIC *** Permanent renal impairment may occur, particularly in patients receiving conventional amphotericin B at doses >1 mg/kg/day, or with pre-existing renal impairment, prolonged therapy, sodium depletion or concurrent nephrotoxic drugs Nephrotoxicity may be reduced by giving an

IV infusion

of sodium chloride 0.9% 250–500 mL over 30–45 minutes immediately before administering amphotericin B 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 20–30 minutes then stop and observe for 30 minutes) Monitor renal function, full blood count, potassium, magnesium and calcium levels Liposomal amphotericin is considerably less nephrotoxic compared with conventional amphotericin B, but is considerably more expensive There are reports of the use of amphotericin in 20% lipid solution being as well tolerated as liposomal amphotericin

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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