NationMaster - Encyclopedia: Flucytosine

Flucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug. In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring [1]. It is isomeric with two other forms of diazine. ... An antifungal drug is medication used to treat fungal infections such as athletes foot, ringworm and candidiasis (thrush), as well as serious systemic infections like cryptococcal meningitis. ... For other meanings, see Drug (disambiguation). ...

It is structurally related to the cytostatic fluorouracil and to floxuridine. It is available in oral and in some countries also in injectable form. A common brand name is Ancobon®. The drug is dispensed in capsules of 250 mg and 500 mg strength. The injectable form is diluted in 250ml saline solution to contain 2.5 grams totally (10mg per ml). The solution is physically incompatible with other drugs including amphotericin B. Chemotherapy is the use of chemical substances to treat disease. ... Fluorouracil (5-FU) is a drug that is used in the treatment of cancer. ... Floxuridine is an oncology drug that belongs to the class known as antimetabolites. ... This article is about brands in marketing. ... In medicine saline is a solution of sodium chloride in sterile water, used commonly for intravenous infusion, rinsing contact lenses, and nasal irrigation or jala neti. ... Amphotericin B (FungilinÂ®, FungizoneÂ®, AbelcetÂ®, AmBisomeÂ®, FungisomeÂ®, AmphocilÂ®, AmphotecÂ®) is a polyene antimycotic drug, used intravenously in systemic fungal infections. ...

Pharmacology

Mechanisms of action

Two major mechanisms of action have been elucidated, one is that the drug is intrafungally converted into the cytostatic flourouracil that undergoes further steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA biosynthesis and disturbs therefore the building of certain essential proteins. The other mechanism is the conversion into 5-flourodeoxyuridinemonophosphate which inhibits fungal DNA synthesis.

Spectrum of susceptible fungi and Resistance

Flucytosine is active in vitro as well as in vivo against some strains of Candida and Cryptococcus. Limited studies demonstrate that flucytosine may be of value against infections with Sporothrix, Aspergillus, Cladosporium, Exophila, and Phialophora. Resistance is quite commonly seen as well in treatment naive patients and under current treatment with flucytosine. In different strains of Candida resistance has been noted to occur in 1 to 50% of all specimens obtained from patients. Candida can have various meanings: Candida is a comedic play by George Bernard Shaw published in 1898 that satirizes socialist reformers in the Church of England. ... Cryptococcus is a genus of fungus. ... Species Aspergillus caesiellus Aspergillus candidus Aspergillus carneus Aspergillus clavatus Aspergillus deflectus Aspergillus flavus Aspergillus fumigatus Aspergillus glaucus Aspergillus nidulans Aspergillus niger Aspergillus ochraceus Aspergillus oryzae Aspergillus parasiticus Aspergillus penicilloides Aspergillus restrictus Aspergillus sojae Aspergillus sydowi Aspergillus terreus Aspergillus ustus Aspergillus versicolor Aspergillus is a genus of around 200 filamentous fungi... Please wikify (format) this article or section as suggested in the Guide to layout and the Manual of Style. ...

Pharmacokinetic data

Flucytosine is well absorbed (75 to 90%) from the gastrointestinal tract. Intake with meals slows the resorption, but does not decrease the amount resorbed. Following an oral dose of 2 grams peak serum levels are reached after approximately 6 hours. The time to peak level decreases with continued therapy. After 4 days peak levels are measured after 2 hours. The drug is eliminated renally. In normal patients flucytosine has reportedly a half-life of 2.5 to 6 hours. In patients with impaired renal function higher serum levels are seen and the drug tends to cumulate in these patients. The drug is mainly excreted unchanged in the urine (90% of an oral dose) and only traces are metabolized and excreted in the feces. Therapeutic serum levels range from 25 to 100mcg/ml. Serum levels in excess of 100mcg are associated with a higher incidence of side-effects. Periodic measurements of serum levels are recommended for all patients and are a must in patients with renal damage. The gastrointestinal tract (GI tract), also called the digestive tract, or the alimentary canal, is the system of organs within multicellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. ...

Human overdose

Symptoms and their severities are unknown, because flucytosine is used under close medical supervision, but expected to be an excess of the usually encountered side effects on the bone marrow, gastrointestinal tract, liver and kidney function. Vigorous hydration and hemodialysis may be helpful to remove the drug from the body. Hemodialysis is particular useful in patients with impaired renal function. An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ... Grays Anatomy illustration of cells in bone marrow. ... The liver is an organ present in vertebrates and some other animals. ... The kidneys filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... It has been suggested that Artificial kidney be merged into this article or section. ...

Human carcinogenity

It is not known if flucytosine is a human carcinogen. The issue has been raised because traces of 5-fluorouracil, which is a known carcinogen, are found in the colon resulting from the metabolization of flucytosine. The hazard symbol for carcinogenic chemicals in the Globally Harmonized System. ...

Indications

Oral flucytosine is indicated for the treatment of serious infections caused by susceptible strains of Candida or Cryptococcus neoformans. It can also be used for the treatment of chronomycosis (chromoblastomycosis), if susceptible strains cause the infection. Flucytosine must not be used as a sole agent in life-threatening fungal infections due to relatively weak antifungal effects and fast development of resistance, but rather in combination with amphotericin B and/or azole antifungals such as fluconazole or itraconazole. Minor infections such as candidal cystitis may be treated with flucytosine alone. In some countries, treatment with slow intravenous infusions for no more than a week is also a therapeutic option, particular if the disease is life-threatening. An azole is a class of five-membered nitrogen heterocyclic ring compounds containing at least one other noncarbon atom, nitrogen, sulfur or oxygen. ... Fluconazole (INN) (IPA: ) is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. ... Itraconazole (marketed as SporanoxÂ® by Janssen Pharmaceutica) is a triazole antifungal agent that is prescribed to patients with fungal infections. ... In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ...

Contraindications and cautions

Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... Brivudine is an anti-viral drug used in the treatment of herpes zoster. ... Chemotherapy is the use of chemical substances to treat disease. ... A blood cell count is a measurement of the levels of a persons haemoglobin, white cell count and platelets. ... Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. ...

Special Patient Groups

Pregnancy and lactation

In animal models (rats), flucytosine has been found to be teratogenic. Sufficient human data does not exist. Pregnant women should be given flucytosine only if the potential benefits exceed the potential harm to the fetus. Teratogenesis is a medical term from the Greek, literally meaning monster making. ... A pregnant woman Pregnancy is the process by which a mammalian female carries a live offspring from conception until it develops to the point where the offspring is capable of living outside the womb. ...

It is not known if flucytosine is distributed in human breast milk. Given the potential risk to the child, the patient should not breastfeed during treatment with flucytosine. Breastfeeding an infant Symbol for breastfeeding (Matt Daigle, Mothering magazine contest winner 2006) Breastfeeding is the feeding of an infant or young child with milk from a womans breasts. ...

Pediatric patients

The efficacy and safety in patients under 18 years of age has not been determined.

Side effects

Anemia (AmE) or anaemia (BrE), from the Greek () meaning without blood, is a deficiency of red blood cells (RBCs) and/or hemoglobin. ... Leukopenia or leukocytopenia refers to a decrease in the number of circulating white blood cells (leukocytes) in the blood. ... Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets. ... Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. ... Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. ... Types 5-7 on the Bristol Stool Chart are often associated with diarrhea Diarrhea (in American English) or diarrhoea (in British English) is a condition in which the sufferer has frequent watery, loose bowel movements (from the Greek word Î´Î¹Î¬ÏÏÎ¿Î¹Î±; literally meaning through-flowing). Acute infectious diarrhea is a common cause... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ... Bilirubin is a yellow breakdown product of normal heme catabolism. ... Jaundice, also known as icterus (attributive adjective: icteric), is a yellowing of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by increased levels of bilirubin in red blooded animals. ... The blood urea nitrogen (BUN) test is a measure of the amount of nitrogen in the blood that comes from urea. ... Chemical structure of creatinine. ... Crystalluria refers to crystals found in the urine when performing a urine test. ... A diagram showing the CNS: 1. ... A hallucination is a sensory perception experienced in the absence of an external stimulus, as distinct from an illusion, which is a misperception of an external stimulus. ... Psychosis is a generic psychiatric term for a mental state often described as involving a loss of contact with reality. Stedmans Medical Dictionary defines psychosis as a severe mental disorder, with or without organic damage, characterized by derangement of personality and loss of contact with reality and causing deterioration... Ataxia (from Greek ataxiÄ, meaning failure to put in order) is unsteady and clumsy motion of the limbs or torso due to a failure of the gross coordination of muscle movements. ... Hearing impairment or deafness is decreased or absent ability to perceive auditory information. ... Paresthesia or paraesthesia (in British English) is a sensation of tingling, pricking, or numbness of a persons skin with no apparent long-term physical effect, more generally known as the feeling of pins and needles or of a limb being asleep. // Transient paresthesia is the temporary sensation of tingling... Parkinsonism describes the common symptoms of Parkinsons disease - tremor, rigidity, akinesia or bradykinesia and postural instability. ... Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness. ... Photosensitivity is the amount to which an object reacts upon receiving photons of light. ... Toxic epidermal necrolysis is a life-threatening and usually drug-induced dermatological condition that occurs more often in women than in men. ... }} In medicine, anaphylaxis is a severe and rapid multi-system allergic reaction. ...

Interactions

For details see Contraindications and Cautions. Flucytosine may increase the toxicity of amphotericin B and vice versa, although the combination may be life-saving and should be used whenever indicated (e.g., cryptococcal meningitis). The cytostatic cytarabine inhibits the antimycotic activity of flucytosine. Amphotericin B (FungilinÂ®, FungizoneÂ®, AbelcetÂ®, AmBisomeÂ®, FungisomeÂ®, AmphocilÂ®, AmphotecÂ®) is a polyene antimycotic drug, used intravenously in systemic fungal infections. ... Cryptococcus neoformans is an encapsulated yeastlike fungus that can live in both plants and animals. ... Cytarabine is a shortened form of cytosine arabinoside, a commonly used chemotherapy agent used mainly in the treatment of leukemia and non-Hodgkin lymphoma. ...

Dosage

The recommended daily dose is 50 to 150mg per kilogram of bodyweight orally, divided in 4 equal doses every 6 hours. If problems exist to swallow a complete single dose, the dose may be given in several partial amounts over 15 minutes. The dose for intravenous infusions is 50mg per kg infused over 20 to 40 minutes every 6 hours. The duration of treatment depends on the clinical situation, but generally does not exceed 7 days.

Use in immunocompromised patients

Serious fungal infections often occur in immunocompromised (e.g. HIV-infected) patients. These patients benefit from combination therapy including flucytosine, but the incidence of side-effects of a combination therapy, particular with amphotericin B, may be higher than in immunocompetent patients. Species Human immunodeficiency virus 1 Human immunodeficiency virus 2 Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS, a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections). ...

Veterinary uses

In some countries, such as Switzerland, flucytosine has been licensed to treat cats, dogs and birds (in most cases together with amphotericin B) for the same indications as in humans.

References

Category: Organofluorides An antifungal drug is medication used to treat fungal infections such as athletes foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. ... A section of the Anatomical Therapeutic Chemical Classification System. ... A section of the Anatomical Therapeutic Chemical Classification System. ... Griseofulvin is an antifungal drug. ... Hitachimycin, also known as stubomycin, is a cyclic polypeptide used as an antibiotic. ... Natamycin, also known as pimaricin, is a polyene antifungal drug. ... Nystatin (Nystan®, Infestat®, Nystamont®) is an polyene antimycotic drug Nystatin is considered one of the clean drugs as it has no proven side effects. ... An azole is a class of five-membered nitrogen heterocyclic ring compounds containing at least one other noncarbon atom, nitrogen, sulfur or oxygen. ... Clotrimazole is a potent, specific inhibitor of p450 enzymes. ... Econazole nitrate is an antifungal medication of the imidazole class. ... Fluconazole (INN) (IPA: ) is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. ... NizoralÂ® logo Ketoconazole is a synthetic antifungal drug used to prevent and treat skin and fungal infections, especially in immunocompromised patients such as those with AIDS. Due to its side-effect profile, it has been superseded by newer antifungals, such as fluconazole and itraconazole. ... Miconazole is an imidazole antifungal agent commonly applied topically (to the skin) or mucus membranes to cure fungal infections. ... Oxiconazole nitrate (US: OxistatÂ®, Canada: OxizoleÂ®) is an antifungal medication typically used as a cream or lotion to treat skin infections such as athletes foot. ... Sertaconazole nitrate (ErtaczoÂ®) is an antifungal medication of the imidazole class. ... Sulconazole nitrate (ExeldermÂ®) is an antifungal medication of the imidazole class. ... Tioconazole is an antifungal medication used to treat infections caused by a fungus or yeast. ... Ciclopirox olamine (also called LoproxÂ®, PenlacÂ® and StieproxÂ®) is a synthetic antifungal agent for topical dermatologic use. ... Ethyl para-hydroxybenzoate, also called ethylparaben, is an ethyl 4-hydroxybenzoate, ethyl ester of p-hydroxybenzoic acid. ... Salicylic acid is the chemical compound with the formula C6H4(OH)CO2H, where the OH group is adjacent to the carboxyl group. ... Selenium sulfide is an antifungal agent often used in shampoos for the treatment of dandruff and seborrheic dermatitis. ... Terbinafine hydrochloride tablets, sold as Lamisil in the U.S., are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (Tinea unguium). ... Tolnaftate is a synthetic over the counter anti-fungal agent. ... Undecylenic Acid is an organic fatty acid derived from natural Castor oil (ricinoleic acid). ... Amphotericin B (FungilinÂ®, FungizoneÂ®, AbelcetÂ®, AmBisomeÂ®, FungisomeÂ®, AmphocilÂ®, AmphotecÂ®) is a polyene antimycotic drug, used intravenously in systemic fungal infections. ... Anidulafungin or Eraxis is an anti-fungal drug manufactured by Pfizer that gained approval by the Food and Drug Administration (FDA) in February 21, 2006 [1]; it was previously known as LY303366. ... Caspofungin is an antifungal drug, the first of a new class termed the echinocandins. ... Griseofulvin is an antifungal drug. ... Itraconazole (marketed as SporanoxÂ® by Janssen Pharmaceutica) is a triazole antifungal agent that is prescribed to patients with fungal infections. ... Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients. ... Terbinafine hydrochloride tablets, sold as Lamisil in the U.S., are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (Tinea unguium). ... Voriconazole (VfendÂ®, Pfizer) is a triazole antifungal medication used to treat serious fungal infections. ... Thiabendazole is a fungicide and parasiticide used primarily to control mold, blight, and other fungally caused diseases in fruits and vegetables. ... Tea tree oil Tea tree oil is a yellowish green-tinged essential oil with a fresh camphoraceous odour. ...

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