Amphotericin B chemical structure
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Amphotericin B

Amphotericin B (Fungilin®, Fungizone®, Abelcet®, AmBisome®, Fungisome®, Amphocil®, Amphotec®) is a polyene antimycotic drug, used intravenously in systemic fungal infections. It was originally extracted from Streptomyces nodosus fungi. Currently the drug is available as plain Amphotericin B, as cholesteryl sulfate complex, as lipid complex, and as liposomal formulation. The latter formulations have been developed to improve tolerability for the patient but may show considerable pharmacokinetic characteristics compared to plain Amphotericin B. more...

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Uses

Oral preparations of amphotericin B are used to treat oral thrush; these are virtually nontoxic. The main i.v. use is in systemic fungal infections (e.g. in immunocompromised patients), and in visceral leishmaniasis. Aspergillosis, cryptococcus infections (e.g. meningitis) and candidiasis are treated with amphotericin B. It is also used empirically in febrile immunocompromised patients who do not respond to broad-spectrum antibiotics.

Method of action

As with other polyene antifungals, amphotericin B associates with ergosterol, a membrane chemical of fungi, forming a pore that leads to K+ leakage and fungal cell death. Recently, however, researchers found evidence that pore formation is not necessarily linked to cell death (i.e. Angewandte Chemie Int. Ed. Engl. 2004). The actual mechanism of action may be more complex and multi-faceted.

Side effects

Very often a most serious acute reaction after the infusion (1 to 3 hours later) is noted consisting of fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, and tachypnea. This reaction sometimes subsides with later applications of the drug and may in part be due to histamine liberation. An increase in prostaglandin-synthesis may also play a role. Often the most difficult decision has to be made, whether the fever is disease- or drug-related. In order to decrease the likelihood and severity of the symptoms, initial doses should be low and increased slowly. The liposomal preperation obviously has a lower incidence of the syndrome. Acetaminophen, pethidine, diphenhydramine and/or hydrocortisone have all be used to treat or prevent the syndrome, but the prophylactic use of these drugs should be limited.

Nephrotoxicity (kidney damage) is a major issue and can be severe and/or irreversible. It is much milder when amphotericin B is delivered in liposomes (AmBisome). Electrolyte imbalances (e.g. hypokalema and hypocalcemia) may also occur.

Increased liver enzymes and hepatotoxicity up to acute liver failure, several forms of anemia and other blood dyscrasias (leukopenia, thrombopenia), serious cardiac arrhythmias (including ventricular fibrillation), and cardiac failure have also been reported frequently. Skin reactions, including serious forms, are also possible.

Interactions

  • Flucytosine : Toxicity of Flucytosine increased and vice versa
  • Diuretics or Cisplatin : Increased renal toxicity and incrised risk of hypokalema
  • Corticosterioids : Increased risk of hypokalema
  • Cytostatic drugs : Increased risk of kidney damage, hypotension and bronchospasms.
  • Other nephrotoxic drugs : Increased risk of serious renal damage. Monitor patients closely.
  • Foscarnet, Ganciclovir, Tenofovir, Adefovir : Risk of hematological and renal side-effects of Amphotericin B increased.
  • Transfusion of Leukocytes : Risk of pulmonal (lung) damage. Space intervalls between the application of Amphotericin B and the transfusion and monitor pulmonal function.

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Successful treatment of an invasive aspergillosis of the skull base and paranasal sinuses with liposomal amphotericin B and itraconazole : An article from: ... Annals of Otology, Rhinology & Laryngology $10.00 Antifungal TX improves chronic rhinosinusitis: the effectiveness of nasal wash with amphotericin B in a small trial points to fungal infection as a factor.(Infectious ... : An article from: Internal Medicine News $5.95
Zygomycosis is rare, but quick action is crucial: treat it with aggressive surgical debridement followed by adjunctive amphotericin B.(Skin Disorders) : An article from: Family Practice News $5.95

Penetration of amphotericin B in human lung tissue after single liposomal amphotericin B infusion
PURPOSE: To investigate the tissue levels and distribution of amphotericin B in lung after i.v. administration of liposomal amphotericin B (L-AmB) in ...
Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial
Delivering the antifungal drug amphotericin B deoxycholate intravenously over a 24-hour period can reduce the number of side effects, according to a study ...
Safety and toxicity of amphotericin B in glucose 5% or intralipid 20% in neutropenic patients with pneumonia or fever of unknown origin: randomised study
Objective: To compare the feasibility of treatment, safety, and toxicity of intravenous amphotericin B deoxycholate prepared in either glucose or intralipid ...
A comparison of fluconazole oral suspension and amphotericin B oral suspension in older patients with oropharyngeal candidosis - Statistical Data Included
Background: the optimum treatment for oropharyngeal candidosis, particularly in older patients, has not been established. Local treatment with nystatin ...
MODULATORY EFFECT OF AMPHOTERICIN B ON TUMOR NECROSIS FACTOR-ALPHA PRODUCTION BY HUMAN MONOCYTES INFECTED WITH PARACOCCIDIOIDES BRASILIENSIS
Nakaira, E. T.1; Scares, A. M. V. C.2; Arila, L. S.3; Matsumoto, L. E.4; Peraçoli, M. T. S.5 1,2,3,4,5IB - UNKSP - Botucatu - Microbiologia e Imunologia ...
SUPERIOR EFFICACY OF THE LIPOSOMAL FORM OF AMPHOTERICIN B COMPARED WITH THE CONVENTIONAL DRUG PRESENTATION IN EARLY STAGES OF THE PARACOCCIDIOIDOMYCOTIC
Scavone, R.1; Burger, E.2 12 Universidade de São Paulo - Departamento de Imunologia Introduction and Objectives: Amphotericin B is the golden standard ...
PRODUCTION OF TUMOR NECROSIS FACTOR ALPHA AND INTERLEUKIN-6 BY HUMAN MONOCYTES STIMULATED IN VITRO WITH PARACOCCIDIOIDES BRASILIENSIS TREATED WITH AMPHOTERICIN
Nakaira, E. T.1; Sugizaki, M. F.2; Soares, A. M. V. C.3; Nascimento, M. P. P.4; Martins, R. A. R.5; Peraçoli, M. T. S.6 1,2,3,4,5,6IB - UNESP - Botucatu ...
Amphotericin B channels in the bacterial membrane: Role of sterol and temperature
ABSTRACT Amphotericin B is an antibiotic that forms ion channels in the membrane of a host cell. The change in permeability produced by these channels ...

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