amphotericin B
antifungal agent· Brands: Fungizone, AmBisome, AbelcetIVNEB
Mechanism of action
Amphotericin B binds to ergosterol, the principal sterol in fungal cell membranes, and forms transmembrane channels. These channels increase membrane permeability, causing leakage of cellular ions and macromolecules, leading to cell death. The drug also interacts with cholesterol in human cell membranes, accounting for its toxicity. Its action is generally fungicidal.
Pharmacokinetics
The drug is not metabolised and is slowly excreted in the bile and urine.
Indications & dosing
Invasive aspergillosis
Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
- adult · IV: 1–1.5 mg/kg daily · Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
Invasive candidiasis
Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
- adult · IV: 0.5–1 mg/kg daily · Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
Cryptococcal meningitis
Often combined with flucytosine; conventional amphotericin B deoxycholate.
- adult · IV: 0.5–0.7 mg/kg daily · Often combined with flucytosine; conventional amphotericin B deoxycholate.
Histoplasmosis
Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
- adult · IV: 0.5–1 mg/kg daily · Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
Mucormycosis
High-dose conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
- adult · IV: 1–1.5 mg/kg daily · High-dose conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
Empirical therapy for suspected fungal infection in neutropenic patients
Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
- adult · IV: 0.5–1 mg/kg daily · Conventional amphotericin B deoxycholate; liposomal formulation has different dosing.
Contraindications & precautions
- Hypersensitivity to amphotericin B or any of its components · Life-threatening reactions such as anaphylaxis have been reported.
- Severe renal impairment (e.g. creatinine clearance < 10 mL/min) · Use only if the potential benefit outweighs the risk; consider lipid formulations and renal support.
- Monitor renal function, serum electrolytes (potassium, magnesium), and full blood count regularly during therapy.
- Administer a test dose (1 mg) before the first infusion to detect severe sensitivity.
- Premedicate with an antipyretic (e.g. paracetamol), an antihistamine, and consider a corticosteroid to reduce infusion reactions.
- Ensure adequate hydration before and during infusion to reduce nephrotoxicity.
- Avoid or carefully monitor concurrent use of other nephrotoxic drugs (e.g. aminoglycosides, ciclosporin).
- Infuse slowly (over 2 to 6 hours) to minimise infusion-related adverse effects.
Adverse effects
- Acute infusion reactions (fever, chills, rigors)
- Nephrotoxicity (increased creatinine, acute kidney injury)serious
- Hypokalaemiaserious
- Hypomagnesaemiaserious
- Anaemia
- Thrombophlebitis at injection site
- Hypotension during infusionserious
- Cardiac arrhythmias (e.g. ventricular fibrillation)serious
- Hepatotoxicity (raised transaminases, hepatitis)serious
Monitoring, pregnancy & toxicity
- Serum creatinine and urea · baseline, then at least twice weekly
- Serum potassium and magnesium · baseline, then at least twice weekly
- Full blood count · baseline, then weekly
- Liver function tests · baseline, then periodic
- Blood pressure and infusion-related reactions · monitor during and after infusion
- Pregnancy: Amphotericin B is the preferred agent for serious systemic fungal infections in pregnancy. It is not known to be teratogenic and can be used when clearly indicated, as benefit usually outweighs risk.
- Toxicity: Infusion-related reactions (fever, chills, rigors, nausea, headache, hypotension) · Premedication with antipyretics, antihistamines, and corticosteroids; slow infusion rate; administer in intensive care setting for severe reactions.
- Toxicity: Nephrotoxicity (increased creatinine, reduced urine output) · Ensure adequate hydration; monitor renal function regularly; consider switching to lipid formulation or reducing dose if toxicity develops.
- Toxicity: Electrolyte disturbances (hypokalemia, hypomagnesemia) · Monitor electrolytes; replace potassium and magnesium as required.
- Toxicity: Haematological toxicity (anaemia, thrombocytopenia, leucopenia) · Monitor full blood count; consider transfusion or growth factors if severe.
Clinical notes
Amphotericin B is used for severe systemic fungal infections, including invasive aspergillosis, candidiasis, cryptococcosis, and mucormycosis. It is also used for visceral leishmaniasis. Dose-limiting nephrotoxicity and infusion reactions are major concerns. Premedication with antipyretics, antihistamines, and corticosteroids can reduce infusion reactions. Sodium loading and close monitoring of renal function and electrolytes are recommended. Liposomal formulations are preferred for many indications due to a better safety profile.
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BNF; local formulary