Flucytosine 5-Fluorocytosine Api Intermediates Antimycotic Drug CAS 2022-85-7

Flucytosine 5-Fluorocytosine Api Intermediates Antimycotic Drug CAS 2022-85-7

Introduction

Flucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug.

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. Flucytosine was first synthesized in 1957 but its antifungal properties were discovered in 1964. The drug is dispensed in capsules of 250 mg and 500 mg strength. The injectable form is diluted in 250 mL saline solution to contain 2.5 g total (10 mg/mL). The solution is physically incompatible with other drugs including amphotericin B.

It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system.

Side Effects

1. Patients treated with drugs compromising bone marrow function (e.g. cytostatics) should be treated carefully. Blood cell counts should be taken very frequently.
2. 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.
3. All patients receiving flucytosine should be under strict medical supervision.
4. Hematological, renal and liver function studies should be done frequently during therapy (initially daily, twice a week for the rest of treatment).
5. Patients with preexisting bone marrow depression and liver impairment should be treated with caution.
6. Antiproliferative actions on bone marrow and GI tissue: Due to the drug's preference for rapidly proliferating tissues, bone marrow depression (anemia, leukopenia, pancytopenia, or even rarely agranulocytosis) may occur. Aplastic anemia has also been seen. Bone marrow toxicity can be irreversible and may cause death, particularly in immunocompromised patients. GI toxicity may be severe or rarely fatal and consists of anorexia, abdominal bloating, abdominal pain, diarrhea, dry mouth, duodenal ulcer, GI hemorrhage, nausea, vomiting, and ulcerative colitis.
7. Liver function: Elevations of liver enzymes and bilirubin, hepatic dysfunction, jaundice and, in one patient, liver necrosis have all been seen. Some fatal cases have been reported; however, the majority of cases was reversible.
8. Renal function: Increased BUN and serum creatinine have been noted. Crystalluria (formation of crystals and excretion in the urine) and acute renal failure have also been seen.
9. Adverse central nervous system effects are frequent and include confusion, hallucinations, psychosis, ataxia, hearing loss, headache, paresthesia, parkinsonism, peripheral neuropathy, vertigo and sedation.
10. Skin reactions: Rash, pruritus, and photosensitivity have all been noticed. Toxic epidermal necrolysis (Lyell's syndrome) may also be encountered and may be life-threatening.
11. Anaphylaxis: Sometimes cases of anaphylaxis consisting of diffuse erythema, pruritus, conjunctival injection, fever, abdominal pain, edema, hypotension and bronchospastic reactions are observed.
12. 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.