Flucytosine

INDICATIONS AND USAGE Flucytosine Capsules, USP are indicated only in the treatment of serious infections caused by susceptible strains of Candida and/or Cryptococcus . Candida: Septicemia, endocarditis and urinary system infections have been effectively treated with flucytosine. Limited trials in pulmonary infections justify the use of flucytosine. Cryptococcus: Meningitis and pulmonary infections have been treated effectively. Studies in septicemias and urinary tract infections are limited, but good responses have been reported. Flucytosine Capsules, USP should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules, USP (see MICROBIOLOGY ).

DOSAGE AND ADMINISTRATION The usual dosage of Flucytosine Capsules, USP is 50 to 150 mg/kg/day administered in divided doses at 6-hour intervals. Nausea or vomiting may be reduced or avoided if the capsules are given a few at a time over a 15-minute period. If the BUN or the serum creatinine is elevated, or if there are other signs of renal impairment, the initial dose should be at the lower level (see WARNINGS ). Flucytosine Capsules, USP should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to Flucytosine Capsules, USP (see MICROBIOLOGY ).

CONTRAINDICATIONS Flucytosine Capsules, USP should not be used in patients with a known hypersensitivity to the drug.

WARNINGS Flucytosine Capsules, USP must be given with extreme caution to patients with impaired renal function. Since flucytosine is excreted primarily by the kidneys, renal impairment may lead to accumulation of the drug. Flucytosine serum concentrations should be monitored to determine the adequacy of renal excretion in such patients. Dosage adjustments should be made in patients with renal insufficiency to prevent progressive accumulation of active drug. Flucytosine Capsules, USP must be given with extreme caution to patients with bone marrow depression. Patients may be more prone to depression of bone marrow function if they: 1) have a hematologic disease, 2) are being treated with radiation or drugs which depress bone marrow, or 3) have a history of treatment with such drugs or radiation. Bone marrow toxicity can be irreversible and may lead to death in immunosuppressed patients. Frequent monitoring of hepatic function and of the hematopoietic system is indicated during therapy.

ADVERSE REACTIONS The adverse reactions which have occurred during treatment with Flucytosine Capsules, USP are grouped according to organ system affected. Cardiovascular: Cardiac arrest, myocardial toxicity, ventricular dysfunction. Respiratory: Respiratory arrest, chest pain, dyspnea. Dermatologic: Rash, pruritus, urticaria, photosensitivity. Gastrointestinal: Nausea, emesis, abdominal pain, diarrhea, anorexia, dry mouth, duodenal ulcer, gastrointestinal hemorrhage, acute hepatic injury including hepatic necrosis with possible fatal outcome in debilitated patients, hepatic dysfunction, jaundice, ulcerative colitis, enterocolitis, bilirubin elevation, increased hepatic enzymes. Genitourinary: Azotemia, creatinine and BUN elevation, crystalluria, renal failure. Hematologic: Anemia, agranulocytosis, aplastic anemia, eosinophilia, leukopenia, pancytopenia, thrombocytopenia, and fatal cases of bone marrow aplasia. Neurologic: Ataxia, hearing loss, headache, paresthesia, parkinsonism, peripheral neuropathy, pyrexia, vertigo, sedation, convulsions. Psychiatric: Confusion, hallucinations, psychosis. Miscellaneous: Fatigue, hypoglycemia, hypokalemia, weakness, allergic reactions, Lyell’s syndrome. To report SUSPECTED ADVERSE REACTIONS , contact Sigmapharm Laboratories, LLC, Pharmacovigilance at 1-855-332-0731 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.