Pharmacology of Amphotericin B

Antifungal drugs – also known as antimycotic drugs – are medicines used to treat fungal infections; amphotericin B being one prominent example. Here, we review indications, mechanism of action, side effects and drug interactions of this important medicine.

Amphotericin B is one of the most powerful antifungal drugs; a drug most commonly administered by slow intravenous infusion.

The drug was originally isolated from the species, Streptomyces nodosus, in 1955.

It is used to treat a wide variety of serious, life-threatening fungal infections including:

  • Aspergillus
  • Leishmaniasis
  • Blastomycosis
  • Candida infections
  • Cryptococcal meningitis
  • Coccidioidomycosis
  • Ocular fungal infections
  • Sporotrichosis
  • Systemic fungal infections
  • Histoplasmosis

Again, amphotericin B is reserved for serious infections. It is not used to treat mild-to-moderate fungal infections.

Mechanism of action

Amphotericin B works by binding to ergosterol, an integral structural component of fungal cell membranes.

When it binds to the fungal cell membrane, the drug forms pores in the cell membrane, leading to leakage of a variety of ions:

  • Potassium
  • Sodium
  • Hydrogen
  • Chloride ions

The loss of these ions is what contributes to and what compromises the fungal cell, leading to cell death.

Side effects

Amphotericin B is widely recognised for its lengthy and serious side effect profile. Here, we list the most prominent side effects.

Within 1-3 hours from administering an injection, patients may experience what is known as “shake and bake” – referring to shaking chills and high fever. Other effects of this initial syndrome include hypotension, nausea, vomiting, headache, dyspnea, weakness and drowsiness.

Patients taking amphotericin B may also experience:

  • Hypokalemia
  • Hypomagnesemia
  • Increased liver enzymes / hepatotoxicity
  • Kidney damage
  • Low blood cell count
  • Cardiac arrhythmias
  • Myocarditis

More recently, liposomal formulations are now available which are associated with a reduced risk of side effects.

Clinical considerations

When we talk about the clinical pharmacology of amphotericin B, we need to think about the following factors:

  • That amphotericin B increases the risk of toxicity with another antifungal drug, flucytosine. For some infections, however, both medicines are taken together but, due to toxicity risks, this warrants close dosage monitoring.
  • That there is an increased risk of hypokalemia / renal toxicity when taken with diuretics or cisplatin.
  • That there is an increased risk of hypokalemia when taken with corticosteroids.
  • That there is an increased risk of renal damage with other nephrotoxic drugs, for example – the aminoglycosides.
  • That hematological side effects are increased when amphotericin B is taken with some HIV medicines, such as tenofovir and adefovir.
  • That amphotericin B is classified as pregnancy category B – meaning that there is “no risk in other studies”.

Amphotericin B remains an essential medicine in the treatment of serious, life-threatening fungal infections.

However, its use must come with the care demanded for a drug of this stature; a medicine associated with the serious side effect and drug interaction profiles we have discussed over the course of this guide.

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