ANCOBON

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 0187-3554

Application: NDA017001

Effective: 20220202

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 ).

WARNINGS ANCOBON must be given with extreme caution to patients with impaired renal function. Since ANCOBON is excreted primarily by the kidneys, renal impairment may lead to accumulation of the drug. ANCOBON 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. ANCOBON 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. 5-Fluorouracil is a metabolite of flucytosine. Dihydropyrimidine dehydrogenase is a key enzyme involved in the metabolism and elimination of 5-fluorouracil. Therefore, the risk of severe drug toxicity is increased when ANCOBON is used in individuals with deficiency in DPD. Possible drug toxicities include mucositis, diarrhea, neutropenia, and neurotoxicity. Determination of DPD activity may be considered where drug toxicity is confirmed or suspected. In the event of suspected drug toxicity, consider stopping ANCOBON treatment.

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 .