Ancobon

• Cardinal Health, Inc.

• Valeant Pharmaceuticals North America LLC

Flucytosine is an antifungal medication that fights infections caused by fungus.

Flucytosine is used to treat serious fungal infections of the blood, lungs, heart, central nervous system, and urinary tract.

Flucytosine is sometimes given with another medicine called amphotericin B.

Flucytosine may also be used for purposes not listed in this medication guide.

Before you take flucytosine, tell your doctor if you have kidney disease.

In some patients this medicine may cause nausea or vomiting. If you are taking more than 1 capsule for each dose, you may space them out over a period of 15 minutes to help lessen the nausea or vomiting. If this does not help or if you have any questions, check with your doctor.

To help clear up your infection completely, keep taking this medicine for the full time of treatment, even if you begin to feel better after a few days. Do not miss any doses.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For fungus infections:
    • Adults and children—Dose is based on body weight. The usual dose is 12.5 to 37.5 milligrams (mg) per kilogram (kg) (5.7 to 17 mg per pound) of body weight every six hours.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

• If you have an allergy to flucytosine or any other part of Ancobon (flucytosine).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are breast-feeding or plan to breast-feed.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Although there is no specific information comparing use of flucytosine in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults.

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Before taking flucytosine, tell your doctor if you

• have kidney disease,
• have a blood or bone marrow disease, or
• are being treated with radiation or a drug that causes bone marrow suppression.

You may not be able to take flucytosine or you may need a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Flucytosine is in the FDA pregnancy category C. This means that it is not known whether flucytosine will be harmful to an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant or could become pregnant during treatment.

It is not known whether flucytosine passes into breast milk. Do not take this medication without first talking to your doctor if you are breast-feeding a baby.

Applies to flucytosine: oral capsule

Gastrointestinal

Gastrointestinal side effects have included nausea, emesis, abdominal pain, diarrhea, anorexia, dry mouth, duodenal ulcer, gastrointestinal hemorrhage, enterocolitis, and ulcerative colitis.[Ref]

Nausea is common at high doses, generally occurs in the first two weeks of therapy, and often resolves with time or temporary dose reduction. Diarrhea is often associated with cramps, occurs most frequently in the first two weeks of therapy, and frequently resolves with time or temporary dose reduction. One case has been reported of a patient on long-term therapy who developed diarrhea which did not resolve spontaneously. X-ray of the small bowel revealed ulceration and the ileocecal valve and distal ileum appeared edematous. Flucytosine was discontinued and the patient improved over the next two weeks.[Ref]

Hepatic

Some patients experience significant increases in liver function tests and may develop signs and symptoms of hepatitis. Liver function test abnormalities generally resolve after discontinuation of flucytosine (the active ingredient contained in Ancobon) [Ref]

Hepatic side effects have included jaundice, hepatic dysfunction, bilirubin elevation, increased hepatic enzymes, and acute hepatic injury including hepatic necrosis with possible fatal outcome in debilitated patients.[Ref]

Hematologic

Hematologic side effects have included anemia, agranulocytosis, aplastic anemia, eosinophilia, leukopenia, pancytopenia, thrombocytopenia, and fatal cases of bone marrow suppression.[Ref]

Bone marrow suppression may range from isolated leukopenia or thrombocytopenia to pancytopenia. Often there is just mild leukopenia or thrombocytopenia which does not require discontinuation of the drug. In most cases the suppression is reversible following discontinuation of flucytosine therapy, but at least one case of fatal, irreversible marrow failure has occurred.[Ref]

Hypersensitivity

Photosensitivity has been reported in one case of a patient receiving long-term flucytosine (the active ingredient contained in Ancobon) The photosensitivity persisted for one year after completion of therapy.

A case of anaphylaxis has been reported. In that case, a patient who had hemophilia and AIDS was receiving flucytosine for oral candidiasis. Flucytosine therapy was started following 10 days of miconazole and the patient developed a fever, erythema, pruritus, tachycardia and hypotension requiring volume support. Rechallenge was attempted one week later with one tablet. The rechallenge resulted in the same signs and symptoms and ran a similar course.[Ref]

Hypersensitivity side effects have included allergic reactions. Rashes have been reported rarely. At least one case of photosensitivity has been reported, in addition to a case of anaphylaxis.[Ref]

Cardiovascular

Cardiovascular side effects have included cardiac arrest, myocardial toxicity, and ventricular dysfunction. Cardiac toxicity with ST elevation has been reported in a 34-year-old woman, with no previous history of heart disease, the day after completing a 2-day flucytosine (the active ingredient contained in Ancobon) therapy.[Ref]

A 34-year-old woman reported severe chest pain the day after completing a 2-day flucytosine therapy. Cardiac echography indicated septo-apico-lateral severe hypokinesia, with left ventricular ejection fraction less than 15%. Aggressive cardiac intensive care with positive inotropic agents, placement of an intra-aortic balloon pump counterpulsation, and milrinone along with continuous veno-venous hemodiafiltration were needed over the 2 weeks of hospitalization before restoration of her cardiovascular status. Patient has not shown further signs of heart problems during the 2 years since this event.[Ref]

Respiratory

Respiratory side effects have included dyspnea, chest pain, and respiratory arrest.[Ref]

Dermatologic

Dermatologic side effects have included rash, pruritus, urticaria, photosensitivity, and Lyell's syndrome.[Ref]

Genitourinary

Genitourinary side effects have included crystalluria.[Ref]

Renal

Renal side effects have included azotemia, creatinine and BUN elevation, and renal failure.[Ref]

Nervous system

Nervous system side effects have included ataxia, hearing loss, headache, paresthesia, parkinsonism, peripheral neuropathy, pyrexia, vertigo, sedation, and convulsions.[Ref]

Psychiatric

Psychiatric side effects have included confusion, hallucinations, and psychosis.[Ref]

Metabolic

Metabolic side effects have included hypoglycemia.

Other

Other side effects have included fatigue and weakness.[Ref]

Some side effects of Ancobon may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Flucytosine has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of species specific teratogenicity. There are no controlled data in human pregnancy. Flucytosine is only recommended for use during pregnancy when benefit outweighs risk.