ANCOBON

INDICATIONS AND USAGE ANCOBON is 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. ANCOBON should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to ANCOBON (see MICROBIOLOGY ).

DOSAGE AND ADMINISTRATION The usual dosage of ANCOBON 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 ). ANCOBON should be used in combination with amphotericin B for the treatment of systemic candidiasis and cryptococcosis because of the emergence of resistance to ANCOBON (see MICROBIOLOGY ).

CONTRAINDICATIONS ANCOBON is contraindicated in patients with a known hypersensitivity to the drug. ANCOBON is contraindicated in patients with known complete dihydropyrimidine dehydrogenase (DPD) enzyme deficiency (see WARNINGS ).

ADVERSE REACTIONS The adverse reactions which have occurred during treatment with ANCOBON 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 Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Interactions Cytosine arabinoside, a cytostatic agent, has been reported to inactivate the antifungal activity of ANCOBON by competitive inhibition. Drugs which impair glomerular filtration may prolong the biological half-life of flucytosine.

DESCRIPTION ANCOBON (flucytosine), an antifungal agent, is available as 250 mg and 500 mg capsules for oral administration. In addition to the active ingredient of flucytosine, each capsule contains corn starch, lactose and talc. The 250 mg capsule shell contains black iron oxide, D&C Yellow No. 10, FD&C Blue No. 1, FD&C Yellow No. 6, gelatin and titanium dioxide. The 500 mg capsule shell contains black iron oxide, gelatin and titanium dioxide. Chemically, flucytosine is 5-fluorocytosine, a fluorinated pyrimidine which is related to fluorouracil and floxuridine. It is a white to off-white crystalline powder with a molecular weight of 129.09 and the following structural formula: Chemical Structure

OVERDOSAGE There is no experience with intentional overdosage. It is reasonable to expect that overdosage may produce pronounced manifestations of the known clinical adverse reactions. Prolonged serum concentrations in excess of 100 mcg/mL may be associated with an increased incidence of toxicity, especially gastrointestinal (diarrhea, nausea, vomiting), hematologic (leukopenia, thrombocytopenia) and hepatic (hepatitis). In the management of overdosage, prompt gastric lavage or the use of an emetic is recommended. Adequate fluid intake should be maintained, by the intravenous route if necessary, since ANCOBON is excreted unchanged via the renal tract. The hematologic parameters should be monitored frequently; liver and kidney function should be carefully monitored. Should any abnormalities appear in any of these parameters, appropriate therapeutic measures should be instituted. Since hemodialysis has been shown to rapidly reduce serum concentrations in anuric patients, this method may be considered in the management of overdosage.

HOW SUPPLIED ANCOBON ® (flucytosine) Capsules are supplied as capsules containing 250 mg and 500 mg flucytosine as follows: NDC Strength Package Configuration Description 0187‐3554‐10 250 mg Bottles of 100 Gray and green capsules imprinted with “ANCOBON ® 250 ICN” 0187‐3555‐10 500 mg Bottles of 100 Gray and white capsules imprinted with “ANCOBON ® 500 ICN” Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Distributed by: Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Bausch Health Companies Inc. Steinbach, MB R5G 1Z7, Canada ANCOBON is a trademark of Bausch Health Companies Inc. or its affiliates. © 2022 Bausch Health Companies Inc. or its affiliates Rev. 02/2022 9578603 20005061