Amphotericin (Fungizone)

Amphotericin - is active against most fungi and yeasts. It also has useful activity against protozoa, including Leishmania spp., Naeglaria and Hartmanella. It is not absorbed from the gut when given orally.When given IV it is highly toxic and side-effects are common.The liposomal and colloidal formulations are less toxic, particularly in terms of nephrotoxicity.

Uses:
Suppress gut carriage of Candida species by the oral route
Severe systemic fungal infections:
Aspergillosis
Candidiasis
Coccidiomycosis
Cryptococcosis
Histoplasmosis

Administration:
• Oral: suppression of gut carriage of Candida 100–200 mg 6 hourly
• IV: systemic fungal infections Initial test dose of 1 mg given over 30 min, then 250 g/kg daily, gradually increased if tolerated to 1 mg/kg daily over 4 days
• For severe infection: 1 mg/kg daily or 1.5 mg/kg daily on alternate days

Available in 20-ml vial containing 50 mg amphotericin Reconstitute with 10 ml WFI (5 mg/ml). Add phosphate buffer to the glucose 5% bag before amphotericin is added. The phosphate buffer label will state the volume to be added; then further dilute the reconstituted solution as follows:

For peripheral administration:
Dilute further with 500 ml glucose 5% (to 0.2 mg/ml) Give over 6 hours

For central administration:
Dilute further with 50–100 ml glucose 5% Give over 6 hours

Prolonged treatment usually needed (duration depends on severity and nature of infection)

Monitor:
Serum potassium, magnesium and creatinine
FBC
LFT

How not to use amphotericin:
Must not be given by rapid IV infusion (arrhythmias)
Not compatible with sodium chloride
There are several formulations of IV amphotericin and they are not interchangeable. Errors of this sort have caused lethal consequences or subtherapeutic doses.

Adverse effects:
Fever and rigors – common in first week. May need paracetamol,
chlorphenamine and hydrocortisone premedication
Nephrotoxicity – major limiting toxicity. Usually reversible
Hypokalaemia/hypomagnesaemia – 25% will need supplements
Anaemia (normochromic, normocytic) – 75%. Due to bone marrow
suppression
Cardiotoxicity – arrhythmias and hypotension with rapid IV bolus
Phlebitis – frequent change of injection site
Pulmonary reactions
GI upset – anorexia, nausea, vomiting

Cautions:
Kidney disease
Concurrent use of other nephrotoxic drugs
Hypokalaemia – increased digoxin toxicity
Avoid concurrent administration of corticosteroids (except to treat
febrile and anaphylactic reactions)

Organ failure:
Renal: use only if no alternative; nephrotoxicity may be reduced with use of Amphocil or AmBisome

Renal replacement therapy:
No further dose modification is required during renal replacement therapy