Flucytosine
Clinical data | |
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Trade names | Ancobon, Ancotil, Cytoflu, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a601132 |
Pregnancy category |
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Routes of administration | By mouth, intravenous |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 75 to 90% (by mouth) |
Protein binding | 2.9 to 4% |
Metabolism | minimal, in the GI tract |
Elimination half-life | 2.4 to 4.8 hours |
Excretion | kidney (90%) |
Identifiers | |
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JSmol) | |
Melting point | 295 to 297 °C (563 to 567 °F) (dec.) |
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Flucytosine, also known as 5-fluorocytosine (5-FC), is an
Common side effects include
Flucytosine was first made in 1957.
Medical uses
Flucytosine by mouth is used for the treatment of serious infections caused by susceptible strains of
Serious fungal infections may occur in those who are immunocompromised. These people benefit from combination therapy including flucytosine, but the incidence of side-effects of a combination therapy, particular with amphotericin B, may be higher.[citation needed]
Pregnancy and breastfeeding
In animal models (rats), flucytosine has been found to be
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.[citation needed]
Children
The efficacy and safety in patients under 18 years of age has not been determined.[citation needed]
Side effects
- Patients treated with drugs compromising bone marrow function (e.g. Blood cell countsshould be taken very frequently.
- Patients with renal disease should receive flucytosine cautiously and in reduced doses. Guidelines for proper dosing exist. Serum level determinations are mandatory for these patients.
- All patients receiving flucytosine should be under strict medical supervision.
- renaland liver function studies should be done frequently during therapy (initially daily, twice a week for the rest of treatment).
- Patients with preexisting bone marrow depression and liver impairment should be treated with caution.
- Antiproliferative actions on bone marrow and GI tissue: Due to the drug's preference for rapidly proliferating tissues, bone marrow depression (duodenal ulcer, GI hemorrhage, nausea, vomiting, and ulcerative colitis.
- Liver function: Elevations of and, in one patient, liver necrosis have all been seen. Some fatal cases have been reported; however, the majority of cases was reversible.
- Renal function: Increased BUN and serum creatinine have been noted. Crystalluria (formation of crystals and excretion in the urine) and acute kidney injury have also been seen.
- Adverse central nervous system effects are frequent and include confusion, hallucinations, psychosis, ataxia, hearing loss, headache, paresthesia, parkinsonism, peripheral neuropathy, vertigo and sedation.
- Skin reactions: Rash, pruritus, and Lyell's syndrome) may also be encountered and may be life-threatening.
- Anaphylaxis: Sometimes cases of anaphylaxis consisting of diffuse erythema, pruritus, conjunctival injection, fever, abdominal pain, edema, hypotension and bronchospastic reactions are observed.
It is not known if flucytosine is a human
Interactions
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.[citation needed]
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 in removing the drug from the body. Hemodialysis is particular useful in patients with impaired renal function.[citation needed]
Pharmacology
Mechanisms of action
Two major mechanisms of action have been elucidated:
- Flucytosine is intrafungally converted into the cytostatic fluorouracil[9] which undergoes further steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA biosynthesis thus disturbing the building of certain essential proteins.
- Flucytosine also undergoes conversion into 5-fluorodeoxyuridinemonophosphate 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
Pharmacokinetic data
Flucytosine is well absorbed (75 to 90%) from the gastrointestinal tract. Intake with meals slows the absorption, but does not decrease the amount absorbed. 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 accumulate. 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 100 μg/ml. Serum levels in excess of 100 μg 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.[citation needed]
Economics
Although a generic, off patent medication in the U.S., as of January 2016, there was only one FDA-approved pharmaceutical supplier,
Other animals
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.[citation needed]
References
- FDA. Retrieved 22 Oct 2023.
- ^ a b c d e f g h "Flucytosine". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
- ISBN 9789241547659.
- ^ "Flucytosine (Ancobon) Use During Pregnancy". www.drugs.com. Archived from the original on 20 December 2016. Retrieved 11 December 2016.
- ISBN 9780470750353. Archivedfrom the original on 2016-12-20.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ PMID 27009249.
- ISBN 9781118777350. Archivedfrom the original on 2016-12-20.
- PMID 10933638.
- ^ "CYTOFLU - Flucytosine". India: Cytoflu. Archived from the original on 2016-02-21. Retrieved 2016-02-02.
External links
- "Flucytosine". Drug Information Portal. U.S. National Library of Medicine.