Amphotericin B

Amphotericin does not distinguish well between ergosterol and cholesterol in cell membranes so serious side effects, such as kidney failure, occur. Lipid formulations reduce the toxicity of the drug when given IV but are very expensive. Use under specialist guidance only and dose appropriately

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• Patients with progressive, potentially life-threatening fungal infections
• Use only under senior specialist direction and dosage advice
• Produced by a strain of Streptomyces nodosus

Mode of action

• Amphotericin B associates with ergosterol, a membrane chemical of fungi
• This forms a pore that leads to K⁺ leakage and fungal cell death.

Indications

• Systemic infection due to Aspergillosis, cryptococcus infections (e.g. meningitis) and candidiasis
• Visceral leishmaniasis, Neutropenic fever, Rhinocerebral phycomycosis seen with DKA

Side effects

• Immediate anaphylaxis - TEST dose must be given
• Commonly fever, chills, nausea, anaphylactoid and other allergic reactions
• Hypotension, Hypokalaemia, Hypomagnesaemia
• Renal tubular acidosis and Nephrotoxicity (less so with liposomal)

Interactions

• Higher risk of nephrotoxicity with Ciclosporin
• Digoxin toxicity especially if hypokalaemia

Dose (Specialist guidance only)

• Under no circumstances should a total daily dose of Amphotericin B 1.5 mg/kg be exceeded. Amphotericin B overdoses can result in potentially fatal cardiac or cardiorespiratory arrest. Amphotericin B must only be used under specialist supervision and direction.
• A single intravenous test dose (1 mg in 20 mL of 5% dextrose solution) administered over 20 to 30 minutes may be preferred first.
• Amphotericin B usual daily dose of 0.25 mg/ kg of body weight with normal cardiac and renal function. Higher doses may be given. Take senior advice. Follow local policies.

References

• Amphotericin in BNF