amphotericin B
American Heritage Dictionary:
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am·pho·ter·i·cin B
(ăm'fə-tĕr'ĭ-sĭn) 
n.
An antibiotic derived from strains of the actinomycete Streptomyces nodosus and used specifically in treating systemic fungal infections.
n.
An antibiotic derived from strains of the actinomycete Streptomyces nodosus and used specifically in treating systemic fungal infections.
[AMPHOTERIC + -IN.]
Drug Info:
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Amphotericin B
Brand names: Amphocin®Fungizone®
Chemical formula:
Amphotericin B Solution for injection
What is this medicine?
AMPHOTERICIN B (am foe TER i sin) is an antifungal medicine. It is used to treat certain kinds of fungal or yeast infections.
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
•heart disease
•kidney disease
•recent medical procedures
•an unusual or allergic reaction to amphotericin B, other medicines, foods, dyes or preservatives
•pregnant or trying to get pregnant
•breast-feeding
How should I use this medicine?
This medicine is for infusion into a vein. It is usually given by a health care professional in a hospital or clinic setting.
If you get this medicine at home, you will be taught how to prepare and give this medicine. Use exactly as directed. Take your medicine at regular intervals. Do not take your medicine more often than directed.
It is important that you put your used needles and syringes in a special sharps container. Do not put them in a trash can. If you do not have a sharps container, call your pharmacist or healthcare provider to get one.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Leave an interval of at least 4 hours between doses of regular capsules and 6 to 8 hours between doses of extended-release capsules. Do not take double or extra doses.What may interact with this medicine?
Do not take this medicine with any of the following medications:
•cidofovir
This medicine may also interact with the following medications:
•certain antibiotics given by injection
•corticotropin
•cyclosporine
•digoxin
•flucytosine
•medicines for fungal infections
•medicines to treat cancer
•muscle relaxers
•pentamidine
•steroid medicines like prednisone or cortisone
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
What should I watch for while using this medicine?
Tell your doctor or health care professional if your symptoms do not improve or if you get new symptoms. Your condition and lab work will be monitored while you are taking this medicine.
What side effects may I notice from receiving this medicine?
Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash or itching, hives, swelling of the lips, mouth, tongue, or throat
•burning, numbness, tingling
•change in amount or color of urine
•changes in hearing
•changes in vision
•chest tightness
•fever, chills
•irregular heart beat, blood pressure
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•seizures
•short of breath, wheezing
•unusual bleeding, bruising
•unusually weak or tired
•yellowing of eyes, skin
Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•body aches, pain
•diarrhea
•headache
•flushing, redness of skin
•loss of appetite
•nausea, vomiting
•pain where injected
•stomach upset, pain
•weight loss
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Where should I keep my medicine?
Keep out of the reach of children.
If you are using this medicine at home, you will be instructed on how to store this medicine. Throw away any unused medicine after the expiration date on the label.
Last updated: 7/1/2002
Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.
Columbia Encyclopedia:
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Amphotericin B
amphotericin B (ăm'fətĕr'ĭsĭn), antibiotic that halts the growth of several disease-causing fungi. Discovered in 1956, it is produced by bacteria of the genus Streptomyces. It is used in lotion or ointment form to treat fungal infections of the skin and is given internally only to patients with potentially fatal fungal infections. Amphotericin B is not effective against bacterial infections.
Oxford Dictionary of Biochemistry:
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amphotericin B
Fungizone; a polyene macrolide antifungal antibiotic produced by Streptomyces spp. It is useful against many mycotic infections, acting as a membrane-active lytic agent. At appropriate concentrations it permeabilizes cells, creating pores formed of five to ten molecules of antibiotic in association with cholesterol. These pores allow the passage of low Mr substances. Because it is active only against sterol-containing membranes, mitochondria are not affected. It interacts preferentially with ergosterol, giving it a high affinity for plant membranes; hence its value as a fungicide. See also polyene antibiotic.
| amphoteric, ampholyte-displacement chromatography, ampholyte | |
| ampicillin, ampicillin-resistant, ampicillin-sensitive |
Saunders Veterinary Dictionary:
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amphotericin B
An antifungal antibiotic produced by Streptomyces nodosus, used to treat deep mycotic infections and also to treat cutaneous and mucocutaneous candidiasis. Potential nephrotoxicity limits its use.
Wikipedia on Answers.com:
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Amphotericin B
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| Systematic (IUPAC) name | |
| (1R,3S,5R,6R,9R, 11R,15S,16R,17R,18S,19E,21E, 23E,25E,27E,29E,31E,33R,35S,36R,37S)- 33-[(3-amino- 3,6-dideoxy- β-D-mannopyranosyl)oxy]- 1,3,5,6,9,11,17,37-octahydroxy- 15,16,18-trimethyl- 13-oxo- 14,39-dioxabicyclo [33.3.1] nonatriaconta- 19,21,23,25,27,29,31-heptaene- 36-carboxylic acid | |
| Clinical data | |
| Trade names | Fungizone |
| AHFS/Drugs.com | monograph |
| Pregnancy cat. | B (US) |
| Legal status | Rx-only, hospitalization recommended. |
| Routes | slow i.v.-infusion only |
| Pharmacokinetic data | |
| Bioavailability | 100% (IV) |
| Metabolism | renal |
| Half-life | initial phase : 24 hours, second phase : approx. 15 days |
| Excretion | 40% found in urine after single cumulated over several days biliar excretion also important |
| Identifiers | |
| CAS number | 1397-89-3  |
| ATC code | A01AB04 A07AA07, G01AA03, J02AA01 |
| PubChem | CID 14956 |
| DrugBank | DB00681 |
| ChemSpider | 10237579 |
| KEGG | D00203 |
| ChEBI | CHEBI:2682 |
| ChEMBL | CHEMBL267345 |
| NIAID ChemDB | 000096 |
| Chemical data | |
| Formula | C47H73NO17 |
| Mol. mass | 923.49 |
| SMILES | eMolecules & PubChem |
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Amphotericin B (Fungilin, Fungizone, Abelcet, AmBisome, Fungisome, Amphocil, Amphotec) is a polyene antifungal drug, often used intravenously for systemic fungal infections. It was originally extracted from Streptomyces nodosus, a 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. Amphotericin A is almost identical to amphotericin B (having a double C=C bond between the 27th and 28th carbons), but has little antifungal activity. Currently, the drug is available as plain amphotericin B, as a cholesteryl sulfate complex (ABCD), as a lipid complex (ABLC), and as a liposomal formulation (LAmB). 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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Contents
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Biosynthesis
The natural route to synthesis includes polyketide synthase components.[1]
Uses
Antifungal
Oral preparations of amphotericin B are used to treat thrush; these are virtually nontoxic, in contrast to typical intravenous therapy (IV) doses.
One of the main intravenous uses is in treating various systemic fungal infections (e.g., in critically ill, comorbidly infected or immunocompromised patients), including cryptococcal meningitis.
Amphotericin B is also commonly used in tissue culture to prevent fungi from contaminating cell cultures. It is usually sold in a concentrated solution, either on its own or in combination with the antibiotics penicillin and streptomycin.
Antiprotozoan
Another IV use is as a drug of last resort in otherwise-untreatable parasitic protozoan infections such as visceral leishmaniasis[2][3] and primary amoebic meningoencephalitis.
Mechanism of action
As with other polyene antifungals, amphotericin B binds with ergosterol, a component of fungal cell membranes, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl−) leakage, which is the primary effect leading to 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).[4] The actual mechanism of action may be more complex and multifaceted.
Mechanism of toxicity
Mammalian and fungal membranes both contain sterols, a primary membrane target for amphotericin B. Because mammalian and fungal membranes are similar in structure and composition, this is one mechanism by which amphotericin B causes cellular toxicity. Amphotericin B molecules can form pores in the host membrane as well as the fungal membrane. This impairment in membrane barrier function can have lethal effects. [5][6][7]
Amphotericin administration is limited by infusion-related toxicity. This is thought to result from innate immune production of proinflammatory cytokines.[6][8]
Side-effects
Amphotericin B is well known for its severe and potentially lethal side-effects. Very often, a serious acute reaction after the infusion (1 to 3 hours later) is noted, consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness. 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. This nearly universal febrile response necessitates a critical (and diagnostically difficult) professional determination as to whether the onset of high fever is a novel symptom of a fast-progressing disease, or merely the induced effect of the drug. To decrease the likelihood and severity of the symptoms, initial doses should be low, and increased slowly. Acetaminophen, pethidine, diphenhydramine, and/or hydrocortisone have all been used to treat or prevent the syndrome, but the prophylactic use of these drugs is often limited by the patient's condition.
Intravenously administered amphotericin B has also been associated with multiple organ damage in therapeutic doses. Nephrotoxicity (kidney damage) is a frequently reported side-effect, and can be severe and/or irreversible. It is much milder when delivered via liposomes (AmBisome), and this is, therefore, the preferred method (see below). The integrity of the liposome is disrupted when it binds to the fungal cell wall, but is not affected by the mammalian cell membrane, thus less toxicity is seen.[9] The association with liposomes decreases the exposure of the kidneys to amphotericin B, which explains less nephrotoxic effects.[10] In addition, electrolyte imbalances (e.g., hypokalemia and hypomagnesemia) may also result. In the liver, increased liver enzymes and hepatotoxicity (up to and including fulminant liver failure) are common. In the circulatory system, several forms of anemia and other blood dyscrasias (leukopenia, thrombopenia), serious cardiac arrhythmias (including ventricular fibrillation), and even frank cardiac failure have been reported. Skin reactions, including serious forms, are also possible.
Interactions
- Flucytosine: Toxicity of flucytosine is increased and allows a lower dose of amphotericin B. Amphotericin B may also facilitate entry of flucystosine into the fungal cell by interfering with the permeability of the fungal cell membrane.
- Diuretics or cisplatin: Increased renal toxicity and increased risk of hypokalemia
- Corticosteroids: Increased risk of hypokalemia
- Cytostatic drugs: Increased risk of kidney damage, hypotension and bronchospasms
- Other nephrotoxic drugs : Increased risk of serious renal damage, monitor kidney function closely
- Foscarnet, ganciclovir, tenofovir, adefovir: Risk of hematological and renal side-effects of amphotericin B are increased.
- Transfusion of leukocytes : Risk of pulmonal (lung) damage occurs. Space the intervals between the application of amphotericin B and the transfusion, and monitor pulmonary function.
Clinical efficacy
Liposomal amphotericin B was effective as empirical therapy or as treatment for confirmed invasive fungal infections in several randomized, double-blind trials (n = 73 − 1095) in adult and pediatric patients.[11]
Liposomal and lipid complex preparations
From studies, it appears that 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.
AmBisome is a liposomal formulation of amphotericin B for 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 Pharmaceuticals in Japan.
Fungisome is a liposomal complex of amphotericin B, and being the latest and cheapest addition to the lipid formulations of amphotericin B, it has many advantages. It is marketed by Lifecare Innovations of India. Other formulations include Amphotec (Intermune) and Abelcet (Sigma-Tau Pharmaceuticals). Abelcet is not a liposomal preparation but rather a lipid complex preparation. Ampholip is a lipid complex formulation of amphotericin B marketed by Bharat Serums & Vaccines Ltd, Mumbai, India.
Oral preparations
A major barrier to the use of amphotericin in resource-poor settings is that it must be given intravenously (except for topical applications). An oral preparation exists, but is not yet commercially available.[12]
References
- ^ Khan N, Rawlings B, Caffrey P (2011-01-26). "A labile point in mutant amphotericin polyketide synthases". Biotechnol Lett.. PMID 21267757.
- ^ Kafetzis DA, Velissariou IM, Stabouli S, Mavrikou M, Delis D, Liapi G (January 2005). "Treatment of paediatric visceral leishmaniasis: amphotericin B or pentavalent antimony compounds?". Int. J. Antimicrob. Agents 25 (1): 26–30. DOI:10.1016/j.ijantimicag.2004.09.011. PMID 15620822. http://linkinghub.elsevier.com/retrieve/pii/S0924-8579(04)00349-8.
- ^ Veerareddy PR, Vobalaboina V, Ali N (December 2008). "Antileishmanial activity, pharmacokinetics and tissue distribution studies of mannose-grafted amphotericin B lipid nanospheres". J Drug Target 17 (2): 140–7. DOI:10.1080/10611860802528833. PMID 19089691. http://www.informaworld.com/openurl?genre=article&doi=10.1080/10611860802528833&magic=pubmed%7C%7C1B69BA326FFE69C3F0A8F227DF8201D0.
- ^ Baginski, M., and J. Czub. "Amphotericin B and Its New Derivatives – Mode of Action." Current Drug Metabolism. 10.5 (2009): 459-69. Print.
- ^ Baginski, M. and Czub, J.. "Amphotericin B and Its New Derivatives – Mode of Action." Current Drug Metabolism. 10.5 (2009): 459–69. Print.
- ^ a b Laniado-Laborin R. and Cabrales-Vargas MN. Amphotericin B: side effects and toxicity. Revista Iberoamericana de Micologia. (2009): 223–7.
- ^ Pfizer. Amphocin. Accessed at http://www.pfizer.com/files/products/uspi_amphocin.pdf on Feb 18 2010.
- ^ Drew, R. Pharmacology of amphotericin B. Uptodate. Sep 2009. Accessed at http://www.utdol.com/online/content/topic.do?topicKey=antibiot/4619&selectedTitle=2~150&source=search_result on Feb 18 2010.
- ^ Jill Adler-Moore,* and Richard T. liposomal formulation, structure, mechanism of action and pre-clinical experience. Journal of Antimicrobial Chemotherapy (2002) 49, 21–30
- ^ J. Czumb, M. Baginksi. Amphotericin B and Its New Derivatives Mode of action. Department of pharmaceutical Technology and Biochemistry. Faculty of Chemistry, Gdnsk University of Technology. 2009, 10-459-469.
- ^ Moen M,Lyseng-Wialliamson KA, Scott LJ.[1].Drugs 2009;69(3):361–392.doi: 10.2165/00003495-200969030-00010.
- ^ Wasan KM, Wasan EK, Gershkovich P, et al. (2009). "Highly Effective oral amphotericin B formulation against murine visceral leishmaniasis". J Infect Dis 200 (3): 357–360. DOI:10.1086/600105. PMID 19545212. http://www.journals.uchicago.edu/doi/full/10.1086/600105.
External links
- AmBisome web site run by Astella Pharma
- "Special issue". Journal of Postgraduate Medicine 51 (Suppl). 2005. http://www.jpgmonline.com/showBackIssue.asp?issn=0022-3859;year=2005;volume=51;issue=5;month=October–December.
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Copyrights:
American Heritage Dictionary
The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved.
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Columbia Encyclopedia
The Columbia Electronic Encyclopedia, Sixth Edition Copyright © 2012, Columbia University Press. Licensed from Columbia University Press. All rights reserved. www.cc.columbia.edu/cu/cup/.
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Oxford Dictionary of Biochemistry
Oxford University Press. Oxford Dictionary of Biochemistry and Molecular Biology © 1997, 2000, 2006 All rights reserved.
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Saunders Veterinary Dictionary
Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved.
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