Clinical data | |
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Trade names | Ancobon, Ancotil, Cytoflu, others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a601132 |
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Routes of administration | By mouth, intravenous |
ATC code | |
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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%) |
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DrugBank | |
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ChEBI | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.016.336 |
Chemical and physical data | |
Formula | C4H4FN3O |
Molar mass | 129.094 g·mol−1 |
3D model (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 antifungal medication. [2] It is specifically used, together with amphotericin B, for serious Candida infections and cryptococcosis. [2] It may be used by itself or with other antifungals for chromomycosis. [2] Flucytosine is used by mouth and by injection into a vein. [2] [3]
Common side effects include bone marrow suppression, loss of appetite, diarrhea, vomiting, and psychosis. [2] Anaphylaxis and other allergic reactions occasionally occur. [2] It is unclear if use in pregnancy is safe for the baby. [4] Flucytosine is in the fluorinated pyrimidine analogue family of medications. [2] It works by being converted into fluorouracil inside the fungus, which impairs its ability to make protein. [2]
Flucytosine was first made in 1957. [5] It is on the World Health Organization's List of Essential Medicines. [6] As of 2016, in the United States the medication cost about US$2,000 per day while in the United Kingdom it is about US$22 per day. [7] It is not available in much of the developing world. [8]
Flucytosine by mouth is used for the treatment of serious infections caused by susceptible strains of Candida or Cryptococcus neoformans . It can also be used for the treatment of chromomycosis (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.[ citation needed ]
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 ]
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.[ citation needed ]
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 ]
The efficacy and safety in patients under 18 years of age has not been determined.[ citation needed ]
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.
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 ]
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 ]
Two major mechanisms of action have been elucidated:
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 , Exophiala , 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.[ citation needed ]
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 ]
Although a generic, off patent medication in the U.S., as of January 2016, there was only one FDA-approved pharmaceutical supplier, Valeant Pharmaceuticals. Due to this monopoly, the cost per 250 mg tablet was $70.46 per tablet for a daily treatment cost of ~$2110/day for a 75 kg adult (165 pounds) adult and $29,591 for a two-week treatment course as of December 2015. [7] This cost of flucytosine is more than 100-fold higher in the U.S. than in the United Kingdom and Europe via Meda AB Pharmaceuticals. Flucytosine tablets are available in India for US$2.00 per tablet via Jolly Healthcare Pvt. Ltd. and are available in 100 tablet packs. [10]
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 ]
Chloramphenicol is an antibiotic useful for the treatment of a number of bacterial infections. This includes use as an eye ointment to treat conjunctivitis. By mouth or by injection into a vein, it is used to treat meningitis, plague, cholera, and typhoid fever. Its use by mouth or by injection is only recommended when safer antibiotics cannot be used. Monitoring both blood levels of the medication and blood cell levels every two days is recommended during treatment.
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.
An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available over the counter (OTC). The evolution of antifungal resistance is a growing threat to health globally.
Nystatin, sold under the brandname Mycostatin among others, is an antifungal medication. It is used to treat Candida infections of the skin including diaper rash, thrush, esophageal candidiasis, and vaginal yeast infections. It may also be used to prevent candidiasis in those who are at high risk. Nystatin may be used by mouth, in the vagina, or applied to the skin.
Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. For certain infections it is given with flucytosine. It is typically given intravenously.
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candidiasis, pityriasis versicolor, dandruff, and seborrheic dermatitis. Taken by mouth it is a less preferred option and only recommended for severe infections when other agents cannot be used. Other uses include treatment of excessive male-patterned hair growth in women and Cushing's syndrome.
Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.
Coccidioides immitis is a pathogenic fungus that resides in the soil in certain parts of the southwestern United States, northern Mexico, and a few other areas in the Western Hemisphere.
Caspofungin is a lipopeptide antifungal drug from Merck & Co., Inc. discovered by James Balkovec, Regina Black and Frances A. Bouffard. It is a member of a new class of antifungals termed the echinocandins. It works by inhibiting the enzyme (1→3)-β-D-glucan synthase and thereby disturbing the integrity of the fungal cell wall. Caspofungin was the first inhibitor of fungal (1→3)-β-D-glucan synthesis to be approved by the United States Food and Drug Administration. Caspofungin is administered intravenously.
Azacitidine, sold under the brand name Vidaza among others, is a medication used for the treatment of myelodysplastic syndrome, myeloid leukemia, and juvenile myelomonocytic leukemia. It is a chemical analog of cytidine, a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative, decitabine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.
Cefaclor, sold under the trade name Ceclor among others, is a second-generation cephalosporin antibiotic used to treat certain bacterial infections such as pneumonia and infections of the ear, lung, skin, throat, and urinary tract. It is also available from other manufacturers as a generic.
Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by Scedosporium or Fusarium. It can be taken by mouth or used by injection into a vein.
Imipenem/cilastatin, sold under the brand name Primaxin among others, is an antibiotic useful for the treatment of a number of bacterial infections. It is made from a combination of imipenem and cilastatin. Specifically it is used for pneumonia, sepsis, endocarditis, joint infections, intra-abdominal infections, and urinary tract infections. It is given by injection into a vein or muscle.
Lamivudine/zidovudine, sold under the brand name Combivir among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains two antiretroviral medications, lamivudine and zidovudine. It is used together with other antiretrovirals. It is taken by mouth twice a day.
Nakaseomyces glabratus is a species of haploid yeast of the genus Nakaseomyces, previously known as Candida glabrata. Despite the fact that no sexual life cycle has been documented for this species, N. glabratus strains of both mating types are commonly found. C. glabrata is generally a commensal of human mucosal tissues, but in today's era of wider human immunodeficiency from various causes, N. glabratus is often the second or third most common cause of candidiasis as an opportunistic pathogen. Infections caused by N. glabratus can affect the urogenital tract or even cause systemic infections by entrance of the fungal cells in the bloodstream (Candidemia), especially prevalent in immunocompromised patients.
Defibrotide, sold under the brand name Defitelio, is a mixture of single-stranded oligonucleotides that is purified from the intestinal mucosa of pigs. It is used to treat veno-occlusive disease of the liver of people having had a bone marrow transplant, with different limitations in the US and the European Union. It works by protecting the cells lining blood vessels in the liver and preventing blood clotting; the way it does this is not well understood.
Gray baby syndrome is a rare but serious, even fatal, side effect that occurs in newborn infants following the accumulation of the antibiotic chloramphenicol. Chloramphenicol is a broad-spectrum antibiotic that has been used to treat a variety of bacteria infections like Streptococcus pneumoniae as well as typhoid fever, meningococcal sepsis, cholera, and eye infections. Chloramphenicol works by binding to ribosomal subunits which blocks transfer ribonucleic acid (RNA) and prevents the synthesis of bacterial proteins. Chloramphenicol has also been used to treat neonates born before 37 weeks of the gestational period for prophylactic purposes. In 1958, newborns born prematurely due to rupture of the amniotic sac were given chloramphenicol to prevent possible infections, and it was noticed that these newborns had a higher mortality rate compared with those who were not treated with the antibiotic. Over the years, chloramphenicol has been used less in clinical practice due to the risks of toxicity not only to neonates, but also to adults due to the risk of aplastic anemia. Chloramphenicol is now reserved to treat certain severe bacteria infections that were not successfully treated with other antibiotic medications.
Benznidazole is an antiparasitic medication used in the treatment of Chagas disease. While it is highly effective in early disease, the effectiveness decreases in those who have long-term infection. It is the first-line treatment given its moderate side effects compared to nifurtimox. It is taken by mouth.
Echinocandins are a class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, the fungal equivalent to bacterial peptidoglycan. Caspofungin, micafungin, and anidulafungin are semisynthetic echinocandin derivatives with limited clinical use due to their solubility, antifungal spectrum, and pharmacokinetic properties.
Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. It can be taken by mouth or applied as a cream to the skin or in the vagina.