Amphotericin B

Concurrent use of corticosteroids, corticotropin ACTH and diuretics (loop and thiazide) may potentiate hypokalemia. ²

Liposomal amphotericin B has been shown to be substantially less toxic than conventional amphotericin B, particularly with respect to nephrotoxicity; however, renal adverse reactions may still occur.

In studies comparing amphotericin B 3 mg/kg daily with higher doses (5, 6 or 10 mg/kg daily), it was found that the incidence rates of increased serum creatinine, hypokalaemia and hypomagnesaemia were notably higher in the high dose groups.

In particular, caution should be exercised when prolonged therapy is required. Regular laboratory evaluation of serum electrolytes, particularly potassium and magnesium as well as renal, hepatic and haematopoietic function should be performed, at least once weekly. This is particularly important in patients receiving concomitant nephrotoxic medications. Renal function should be closely monitored in these patients. Due to the risk of hypokalaemia, appropriate potassium supplementation may be required during the course of amphotericin B administration. If clinically significant reduction in renal function or worsening of other parameters occurs, consideration should be given to dose reduction, treatment interruption or discontinuation.

Amphotericin-B-induced hypokalemia may potentiate digitalis toxicity.

Amphotericin-B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g. tubocurarine).

Concurrent use of antineoplastic agents may enhance the potential for renal toxicity, bronchospasm and hypotension. Antineoplastic agents should be given concomitantly with caution.

Concurrent administration of amphotericin B with other nephrotoxic agents (for example ciclosporin, aminoglycosides, polymixins, tacrolimus and pentamidine) may enhance the potential for drug-induced renal toxicity in some patients. However, in patients receiving concomitant ciclosporin and/or aminoglycosides, amphotericin B was associated with significantly less nephrotoxicity compared to amphotericin B. Regular monitoring of renal function is recommended in patients receiving amphotericin B with any nephrotoxic medications.

No evidence of benefit from the use of flucytosine with amphotericin B has been observed. Whilst synergy between amphotericin and flucytosine has been reported, concurrent use may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion.

Anaphylaxis and anaphylactoid reactions have been reported in association with amphotericin B infusion. Allergic type reactions, including severe infusion-related reactions can occur during administration of amphotericin-containing products, including amphotericin B. Therefore, administration of a test dose is still advisable before a new course of treatment. If a severe allergic or anaphylactic/anaphylactoid reaction occurs, the infusion should be immediately discontinued and the patient should not receive further infusion of amphotericin B.

The safety of amphotericin B in pregnant women has not been established.

Systemic fungal infections have been successfully treated in pregnant women with conventional amphotericin B without obvious effect on the fetus, but the number of cases reported is insufficient to draw any conclusions on the safety of amphotericin B in pregnancy.

Amphotericin B should only be used during pregnancy if the possible benefits to be derived outweigh the potential risks to the mother and fetus.

It is unknown whether amphotericin B is excreted in human breast milk. A decision on whether to breastfeed while receiving amphotericin B should take into account the potential risk to the child as well as the benefit of breast feeding for the child and the benefit of amphotericin B therapy for the mother.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

No studies on the effects on the ability to drive and use machines have been performed. Some of the undesirable effects of amphotericin B presented below may impact the ability to drive and use machines.