indication

Used to treat potentially life threatening fungal infections.

pharmacology

Amphotericin B shows a high order of in vitro activity against many species of fungi. Histoplasma capsulatum, Coccidioides immitis, Candida species, Blastomyces dermatitidis, Rhodotorula, Cryptococcus neoformans, Sporothrix schenckii, Mucor mucedo, and Aspergillus fumigatus are all inhibited by concentrations of amphotericin B ranging from 0.03 to 1.0 mcg/mL in vitro. While Candida albicans is generally quite susceptible to amphotericin B, non-albicans species may be less susceptible. Pseudallescheria boydii and Fusarium sp. are often resistant to amphotericin B. The antibiotic is without effect on bacteria, rickettsiae, and viruses.

mechanism of action

Amphotericin B is fungistatic or fungicidal depending on the concentration obtained in body fluids and the susceptibility of the fungus. The drug acts by binding to sterols (ergosterol) in the cell membrane of susceptible fungi. This creates a transmembrane channel, and the resultant change in membrane permeability allowing leakage of intracellular components. Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of amphotericin B and the azoles. Amphotericin B, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

toxicity

Oral, rat: LD₅₀ = >5 gm/kg. Amphotericin B overdoses can result in cardio-respiratory arrest.

biotransformation

Exclusively renal

absorption

Bioavailability is 100% for intravenous infusion.

half life

An elimination half-life of approximately 15 days follows an initial plasma half-life of about 24 hours.

drug interactions

Colistimethate: Amphotericin B may enhance the nephrotoxic effect of Colistimethate. Due to the potential for additive or synergistic nephrotoxicity between colistimethate and other nephrotoxic drugs, such as amphotericin B, this combination should be avoided whenever possible. If these agents must be used together, patients' renal function should be monitored closely.

Cyclosporine: Monitor for nephrotoxicity

Tacrolimus: Additive renal impairment may occur during concomitant therapy with Amphotericin B. Use caution during concomitant therapy.

Tobramycin: Increased risk of nephrotoxicity