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| {{drugbox | | | __NOTOC__ |
| | IUPAC_name = (1R-(1R*,3S*,5R*,6R*,9R*,11R*,15S*,16R*,17R*,<BR>18S*,19E,21E,23E,25E,27E,29E,31E,33R*,<BR>35S*,36R*,37S*))-33-((3-Amino-3,6-dideoxy-beta-<BR>D-mannopyranosyl)oxy)-<BR>1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl<BR>-13-oxo-14,39-dioxabicyclo(33.3.1)nonatriaconta-<BR>19,21,23,25,27,29,31-heptaene-36-<BR>carboxylic acid
| | {{Amphotericin B}} |
| | image = Amphotericin B.png
| | {{CMG}} |
| | width = 200px
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| | CAS_number = 1397-89-3
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| | ATC_prefix = A01
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| | ATC_suffix = AB04
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| | ATC_supplemental= {{ATC|A07|AA07}}, {{ATC|G01|AA03}}, {{ATC|J02|AA01}}
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| | PubChem = 14956
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| | DrugBank = APRD00797
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| | chemical_formula =
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| | C=47 | H=73 | N=1 | O=17
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| | molecular_weight = 924.084
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| | bioavailability = 100% (IV)
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| | metabolism = renal
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| | elimination_half-life = initial phase : 24 hours, <br/> second phase : approx. 15 days
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| | excretion = 40% found in urine after single cumulated over several days <br/> biliar excretion also important
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| | pregnancy_US = B
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| | pregnancy_category =
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| | legal_status = Rx-only, hospitalization recommended.
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| | routes_of_administration = slow i.v.-infusion only
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| }} | |
| {{SI}} | |
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| ==Overview== | | ==Overview== |
| '''Amphotericin B''' (Fungilin, Fungizone, Abelcet, AmBisome, Fungisome, Amphocil, Amphotec) is a [[polyene]] [[antifungal]] [[medication|drug]], often used [[intravenous]]ly for systemic [[fungi|fungal]] [[infection]]s. It was originally extracted from ''[[Streptomyces]] [[Streptomyces nodosus|nodosus]]'', a [[hypha|filamentous]] [[bacterium]], in 1955 at the Squibb Institute for Medical Research from cultures of an undescribed streptomycete isolated from the soil collected in the [[Orinoco River]] region of [[Venezuela]]. Its name originates from the chemical's [[amphoteric]] properties. Two amphotericins, Amphotericin A and Amphotericin B are known, but only B is used clinically because it is significantly more active [[in vivo]].
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| 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 considerably different pharmacokinetic characteristics compared to plain Amphotericin B.
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| ==Uses== | | ==Category== |
| Oral preparations of amphotericin B are used to treat oral [[candidiasis|thrush]]; these are virtually nontoxic. The main i.v. use is in systemic [[fungal infection]]s (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 [[fever|febrile]] immunocompromised patients who do not respond to [[broad-spectrum antibiotic]]s.
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| ==Mechanism of action== | | ==US Brand Names== |
| As with other polyene antifungals, amphotericin B associates with [[ergosterol]], a membrane chemical of fungi, forming a pore that leads to [[potassium|K<sup>+</sup>]] 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.
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| Amphotericin B is believed to interact with membrane sterols ([[ergosterol]]) to produce an aggregate that forms a transmembrane channel. Intermolecular hydrogen bonding interactions among hydroxyl, carboxyl and amino groups stabilize the channel in its open form, destroying activity and allowing the cytoplasmic contents to leak out.
| | ==FDA Package Insert== |
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| ==Side effects==
| | ''' [[Amphotericin B description|Description]]''' |
| Very often a serious acute reaction after the infusion (1 to 3 hours later) is noted consisting of [[fever]], shaking [[chills]], [[hypotension]], [[anorexia (symptom)|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 preparation obviously has a lower incidence of the syndrome. Acetaminophen, pethidine, diphenhydramine and/or hydrocortisone have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs should be limited.
| | '''| [[Amphotericin B clinical pharmacology|Clinical Pharmacology]]''' |
| | '''| [[Amphotericin B microbiology|Microbiology]]''' |
| | '''| [[Amphotericin B indications and usage|Indications and Usage]]''' |
| | '''| [[Amphotericin B contraindications|Contraindications]]''' |
| | '''| [[Amphotericin B warnings and precautions|Warnings and Precautions]]''' |
| | '''| [[Amphotericin B adverse reactions|Adverse Reactions]]''' |
| | '''| [[Amphotericin B drug interactions|Drug Interactions]]''' |
| | '''| [[Amphotericin B overdosage|Overdosage]]''' |
| | '''| [[Amphotericin B clinical studies|Clinical Studies]]''' |
| | '''| [[Amphotericin B dosage and administration|Dosage and Administration]]''' |
| | '''| [[Amphotericin B how supplied|How Supplied]]''' |
| | '''| [[Amphotericin B labels and packages|Labels and Packages]]''' |
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| [[Nephrotoxicity]] (kidney damage) is a major issue and can be severe and/or irreversible.
| | ==Mechanism of Action== |
| It is much milder when amphotericin B is delivered in [[liposome]]s (AmBisome). Electrolyte imbalances (e.g. hypokalemia and hypocalcemia) may also occur.
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| 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.
| | ==References== |
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| ==Interactions==
| | {{Reflist|2}} |
| * [[Flucytosine]] : Toxicity of Flucytosine increased and vice versa
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| * Diuretics or Cisplatin : Increased renal toxicity and incrised risk of hypokalemia
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| * Corticosterioids : Increased risk of hypokalemia
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| * Cytostatic drugs : Increased risk of kidney damage, hypotension and bronchospasms.
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| * Other nephrotoxic drugs : Increased risk of serious renal damage. Monitor patients closely.
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| * Foscarnet, Ganciclovir, Tenofovir, Adefovir : Risk of hematological and renal side-effects of Amphotericin B increased.
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| * Transfusion of Leukocytes : Risk of pulmonal (lung) damage. Space intervals between the application of Amphotericin B and the transfusion and monitor pulmonary function.
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| ==Liposomal and lipid complex preparations==
| | [[Category:Antibiotics]] |
| From studies it appears that [[liposome|liposomal]] amphotericin B preparations exhibit fewer side-effects while having similar efficacy. Various preparations have recently been introduced. All of these are more expensive than plain Amphotericin B.
| | [[Category:Wikinfect]] |
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| ''AmBisome'' is a liposomal formulation of amphotericin B for [[Injection (medicine)|injection]], developed by [[NeXstar Pharmaceuticals]] (acquired by [[Gilead Sciences]] in 1999). It is marketed by Gilead in Europe and licensed to [[Astellas Pharma]] (formerly Fujisawa Pharmaceuticals) for marketing in the USA, and [[Sumitomo Chemical Co.|Sumitomo Pharmaceuticals]] in Japan.
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| ''Fungisome'' is a liposomal complex of Amphotericin B and being the latest and cheapest addition to the lipid formulations of Amphotericin B has many advantages. It is marketed by [[Lifecare Innovations]] of India. Other formulations include Amphotec ([[Intermune]]) and Abelcet ([[Enzon Pharmaceuticals]]).
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| Abelcet is not a liposomal preparation but rather a lipid complex preparation.
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| ==External links==
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| *[http://www.fungisome.com Fungisome web site] run by [[Lifecare Innovations]]
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| *[http://www.ambisome.com AmBisome web site] run by [[Astella Pharma]]
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| * {{cite journal | journal=Journal of Postgraduate Medicine | year=2005 | volume=51 | issue=Suppl | title=Special issue | url=http://www.jpgmonline.com/showBackIssue.asp?issn=0022-3859;year=2005;volume=51;issue=5;month=October-December}}
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| {{Stomatological preparations}}
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| {{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
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| {{Antifungals}}
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| {{Gynecological anti-infectives and antiseptics}}
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| [[Category:Gilead Sciences]] | |
| [[Category:Antifungals]] | |
| [[Category:Polyketide antibiotics]]
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| [[de:Amphotericin B]]
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| [[fr:Amphotéricine B]]
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| [[hu:Amfotericin B]]
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| [[ja:アムホテリシンB]]
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| [[pt:Anfotericina B]]
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| [[zh:两性霉素B]]
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| {{jb1}}
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