Ancobon

Other Systemic Antifungals

Available in only two strengths of capsules.
To decrease the incidence and severity of nausea and vomiting, administer the dose over 15 minutes.

For pediatric patients, a suspension may be made. The contents of two 500 mg capsules can be mixed with 100 mL of distilled water to give a 10 mg/mL suspension.
The suspension is stable for 1 week at room temperature when protected from light. Maintain pH of the suspension between 5—6.5.

NOTE: Flucytosine is not approved by the FDA for intrathecal administration.
Not indicated due to the excellent CSF:serum distribution after oral administration.

agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
seizures / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
respiratory arrest / Rapid / Incidence not known

leukopenia / Delayed / Incidence not known
bone marrow suppression / Delayed / Incidence not known
anemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
colitis / Delayed / Incidence not known
crystalluria / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
pseudoparkinsonism / Delayed / Incidence not known
hallucinations / Early / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
confusion / Early / Incidence not known
ataxia / Delayed / Incidence not known
psychosis / Early / Incidence not known
dyspnea / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypoglycemia / Early / Incidence not known
hypokalemia / Delayed / Incidence not known

weakness / Early / Incidence not known
fever / Early / Incidence not known
fatigue / Early / Incidence not known
nausea / Early / Incidence not known
anorexia / Delayed / Incidence not known
xerostomia / Early / Incidence not known
diarrhea / Early / Incidence not known
vomiting / Early / Incidence not known
abdominal pain / Early / Incidence not known
urticaria / Rapid / Incidence not known
pruritus / Rapid / Incidence not known
photosensitivity / Delayed / Incidence not known
rash / Early / Incidence not known
paresthesias / Delayed / Incidence not known
drowsiness / Early / Incidence not known
vertigo / Early / Incidence not known
headache / Early / Incidence not known

Use flucytosine with extreme caution in patients with renal impairment. Since flucytosine is excreted primarily by the kidneys, renal impairment may lead to accumulation of the drug. Monitor kidney function and flucytosine serum concentrations during therapy to determine the adequacy of renal excretion in patients with renal disease. Adjust the flucytosine dose in patients with renal impairment or renal failure to prevent progressive accumulation of active drug. Measurement of serum creatinine should be determined by the Jaffe reaction due to laboratory test interference with flucytosine; flucytosine does not interfere with the determination of creatinine values by this method.

Use flucytosine with caution in patients with hepatic disease or jaundice; also use with caution in neonates with hyperbilirubinemia. Flucytosine can cause hepatotoxicity (i.e., hepatitis and jaundice), and worsening of previously existing hepatic dysfunction. Monitor liver function tests (AST, ALT, and alkaline phosphatase) frequently throughout therapy.

Ancobon

Rx

Fluorinated pyrimidine antifungal agent; structurally similar to fluorouracil and floxuridine; used mainly in combination with amphotericin B for cryptococcal meningitis; use has decreased due to availability of new antifungals.

50 to 150 mg/kg/day PO divided every 6 hours in combination with amphotericin B. Adjust dosage, if necessary, based on serum flucytosine concentrations.

25 mg/kg/dose PO 4 times daily in combination with amphotericin B (conventional or lipid formulation) is the general dosage for most infections. Adjust dosage, if necessary, based on serum flucytosine concentrations.

50 to 150 mg/kg/day PO divided every 6 hours in combination with amphotericin B (conventional or lipid formulation) is the most commonly reported dosage range; adjust dosage based on serum flucytosine concentrations. Rarely, up to 200 mg/kg/day PO has been used; however, based on pharmacokinetic data, that dosage is likely to be excessive for most neonates. Although most cases in the literature were administered flucytosine in 4 divided doses per day, pharmacokinetic data suggest that a longer interval (i.e., 50 to 100 mg/kg/day given every 24 hours) may be sufficient in neonates due to a longer elimination half-life, immature renal function, and the time-dependent pharmacodynamic activity of flucytosine. The addition of flucytosine to amphotericin B therapy is maybe used as part of salvage therapy.

50 to 150 mg/kg/day PO in divided doses every 6 hours , or alternately, the Infectious Diseases Society of America (IDSA) recommends 25 mg/kg/dose PO 4 times daily in combination with a lipid amphotericin B product. However, surgical management is the primary recommendation. Adjust dosage, if necessary, based on serum flucytosine concentrations. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment.

25 mg/kg/dose PO 4 times daily in combination with a lipid amphotericin B product is recommended by the Infectious Diseases Society of America (IDSA); however, surgical management is the primary recommendation. Adjust dosage, if necessary, based on serum flucytosine concentrations. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment.

50 to 150 mg/kg/day PO divided every 6 hours in combination with amphotericin B (conventional or lipid formulation) is the most commonly reported dosage range ; adjust dosage based on serum flucytosine concentrations. Rarely, up to 200 mg/kg/day PO has been used ; however, based on pharmacokinetic data, that dosage is likely to be excessive for most neonates. Although most cases in the literature were administered flucytosine in 4 divided doses per day, pharmacokinetic data suggest that a longer interval (i.e., 50 to 100 mg/kg/day given every 24 hours) may be sufficient in neonates due to a longer elimination half-life, immature renal function, and the time-dependent pharmacodynamic activity of flucytosine. For endocarditis, treat for at least 6 weeks after valve replacement. For infected cardiac hardware, treat for at least 4 to 6 weeks after hardware removal. When valve replacement or hardware removal is not possible, chronic suppressive therapy with fluconazole is recommended after initial treatment. The addition of flucytosine to amphotericin B therapy is not routinely recommended for neonatal candidiasis by the Infectious Diseases Society of America (IDSA).

25 mg/kg/dose PO 4 times daily for 7 to 10 days. Guidelines suggest flucytosine for C. glabrata. Adjust dosage, if necessary, based on serum flucytosine concentrations.

25 mg/kg/dose PO 4 times daily for 7 to 10 days. Guidelines suggest flucytosine for C. glabrata. Adjust dosage, if necessary, based on serum flucytosine concentrations.

25 mg/kg/dose PO 4 times daily for 14 days. Guidelines suggest flucytosine for C. glabrata as monotherapy or in combination with amphotericin B. Adjust dosage, if necessary, based on serum flucytosine concentrations.

25 mg/kg/dose PO 4 times daily for 14 days. Guidelines suggest flucytosine for C. glabrata as monotherapy or in combination with amphotericin B. Adjust dosage, if necessary, based on serum flucytosine concentrations.

25 mg/kg/dose PO 4 times daily for 7 to 14 days. Adjust dosage, if necessary, based on serum flucytosine concentrations.

25 mg/kg/dose PO 4 times daily for 7 to 14 days. Adjust dosage, if necessary, based on serum flucytosine concentrations.

50 to 150 mg/kg/day PO in divided doses every 6 hours , or alternately, an initial dosage of 25 mg/kg/dose PO 4 times daily in combination with amphotericin B (conventional or lipid formulation) or fluconazole (alternative for HIV-infected patients who cannot tolerate amphotericin B) is recommended by clinical practice guidelines as induction therapy. Adjust dosage, if necessary, based on serum flucytosine concentrations. Induction therapy is usually for 2 weeks; however, the duration of initial therapy depends on site and severity of infection, clinical response, and underlying risk factors. For cerebral cryptococcomas, give induction therapy for at least 6 weeks. For persistence or relapse of cryptococcosis, reinstate induction therapy for 4 to 10 weeks. Consolidation and maintenance therapy with fluconazole should follow acute treatment.

25 mg/kg/dose PO 4 times daily in combination with amphotericin B (conventional or lipid formulation) or fluconazole (alternative for HIV-infected patients who cannot tolerate amphotericin B) is recommended by clinical practice guidelines as induction therapy. Adjust dosage, if necessary, based on serum flucytosine concentrations. Induction therapy is usually for 2 weeks; however, the duration of initial therapy depends on site and severity of infection, clinical response, and underlying risk factors. Consolidation and maintenance therapy with fluconazole should follow acute treatment.

50 to 150 mg/kg/day PO in divided doses every 6 hours , or alternately, the Infectious Diseases Society of America (IDSA) recommends 25 mg/kg/dose PO 4 times daily in combination with liposomal amphotericin B. Adjust dosage, if necessary, based on serum flucytosine concentrations. Treatment should continue until all signs and symptoms and CSF and radiologic abnormalities have resolved. Intraventricular devices should be removed.

25 mg/kg/dose PO 4 times daily in combination with liposomal amphotericin B is recommended by the Infectious Diseases Society of America (IDSA) ; however, 37.5 mg/kg/dose PO every 6 hours has also been used in children with Candida meningitis. Adjust dosage, if necessary, based on serum flucytosine concentrations. Treatment should continue until all signs and symptoms and CSF and radiologic abnormalities have resolved. Intraventricular devices should be removed.

50 to 150 mg/kg/day PO divided every 6 hours in combination with amphotericin B (conventional or lipid formulation) is the most commonly reported dosage range ; adjust dosage based on serum flucytosine concentrations. Rarely, up to 200 mg/kg/day PO has been used ; however, based on pharmacokinetic data, that dosage is likely to be excessive for most neonates. Although most cases in the literature were administered flucytosine in 4 divided doses per day, pharmacokinetic data suggest that a longer interval (i.e., 50 to 100 mg/kg/day given every 24 hours) may be sufficient in neonates due to a longer elimination half-life, immature renal function, and the time-dependent pharmacodynamic activity of flucytosine. Treatment should continue until all signs and symptoms and CSF and radiologic abnormalities have resolved. Intraventricular devices should be removed. The addition of flucytosine to amphotericin B therapy is not routinely recommended for neonatal candidiasis by the Infectious Diseases Society of America (IDSA). Treatment outcomes of combination therapy with amphotericin B and flucytosine for candidiasis in neonates have been conflicting. An early study revealed improvement in 15 patients (n = 7 neonates) on combination therapy. In a study of extremely low birth weight neonates with candidiasis (total n = 320; with positive culture for Candida in CSF, n = 27), clearance of CSF was longer in neonates who received combination therapy compared with amphotericin B alone.

25 mg/kg/dose PO 4 times daily in combination with liposomal amphotericin B is recommended by the Infectious Diseases Society of America (IDSA) for fluconazole/voriconazole-resistant infections. Adjust dosage, if necessary, based on serum flucytosine concentrations. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions.

50 to 150 mg/kg/day PO divided every 6 hours in combination with amphotericin B (conventional or lipid formulation) is the most commonly reported dosage range ; adjust dosage based on serum flucytosine concentrations. Rarely, up to 200 mg/kg/day PO has been used ; however, based on pharmacokinetic data, that dosage is likely to be excessive for most neonates. Although most cases in the literature were administered flucytosine in 4 divided doses per day, pharmacokinetic data suggest that a longer interval (i.e., 50 to 100 mg/kg/day given every 24 hours) may be sufficient in neonates due to a longer elimination half-life, immature renal function, and the time-dependent pharmacodynamic activity of flucytosine. Treat for at least 4 to 6 weeks with final duration depending on resolution of lesions. The addition of flucytosine to amphotericin B therapy is not routinely recommended for neonatal candidiasis by the Infectious Diseases Society of America (IDSA).

150 mg/kg/day PO in divided doses every 6 hours. Flucytosine is usually administered concurrently with parenteral amphotericin B for disseminated fungal disease due to rapid development of resistance to flucytosine alone.

1 g PO once daily for at least 14 days after catheter removal in conjunction with amphotericin B. Adjust dosage, if necessary, based on serum flucytosine concentrations.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Adults
Initial dosage adjustment:
CrCl more than 40 mL/minute: No dosage adjustment needed.
CrCl 20 to 40 mL/minute: Extend initial dosing interval to every 12 hours. Adjust dosage, if necessary, based on serum flucytosine concentrations.
CrCl 10 to 19 mL/minute: Extend initial dosing interval to every 24 hours. Adjust dosage, if necessary, based on serum flucytosine concentrations.
CrCl less than 10 mL/minute: Extend initial dosing interval to every 48 hours. Adjust dosage, if necessary, based on serum flucytosine concentrations.
 
Pediatric patients
The following initial dosage adjustments are based on the usual recommended dose in children of 25 to 37.5 mg/kg/dose PO every 6 hours:
CrCl 30 to 50 mL/minute/1.73 m2: Extend initial dosing interval to every 8 hours. Adjust dosage, if necessary, based on serum flucytosine concentrations.
CrCl 10 to 29 mL/minute/1.73 m2: Extend initial dosing interval to every 12 hours. Adjust dosage, if necessary, based on serum flucytosine concentrations.
CrCl less than 10 mL/minute/1.73 m2: Extend initial dosing interval to every 24 hours. Adjust dosage, if necessary, based on serum flucytosine concentrations.
 
Intermittent hemodialysis
Adults
25 to 50 mg/kg PO every 48 to 72 hours, given immediately after dialysis. Adjust dosage, if necessary, based on serum flucytosine concentrations.
 
Pediatric patients
25 to 37.5 mg/kg/dose PO every 24 hours. Adjust dosage, if necessary, based on flucytosine serum concentrations.
 
Peritoneal dialysis
Adults
500 mg to 1 g PO every 24 hours. Adjust dosage, if necessary, based on flucytosine serum concentrations.
 
Pediatric patients
25 to 37.5 mg/kg/dose PO every 24 hours. Adjust dosage, if necessary, based on flucytosine serum concentrations.
 
Continuous renal replacement therapy (CRRT)
Adults
Extend initial dosing interval to every 12 to 24 hours. Adjust dosage, if necessary, based on flucytosine serum concentrations.
 
Pediatric patients
25 to 37.5 mg/kg/dose PO every 8 hours. Adjust dosage, if necessary, based on flucytosine serum concentrations.

Abacavir; Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression, such as flucytosine, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted.
Amphotericin B lipid complex (ABLC): (Minor) Amphotericin B may increase the toxicity of flucytosine by possibly increasing flucytosine cellular uptake and/or impairing flucytosine renal excretion. However, flucytosine can have synergistic effects when used with amphotericin B, and these two drugs frequently are used together to treat cryptococcal infections. This combination may allow for a reduction in the total daily dose of amphotericin B. However, amphotericin B-induced reductions in renal function can increase bone marrow toxicity from flucytosine.
Amphotericin B liposomal (LAmB): (Minor) Amphotericin B may increase the toxicity of flucytosine by possibly increasing flucytosine cellular uptake and/or impairing flucytosine renal excretion. However, flucytosine can have synergistic effects when used with amphotericin B, and these two drugs frequently are used together to treat cryptococcal infections. This combination may allow for a reduction in the total daily dose of amphotericin B. However, amphotericin B-induced reductions in renal function can increase bone marrow toxicity from flucytosine.
Amphotericin B: (Minor) Amphotericin B may increase the toxicity of flucytosine by possibly increasing flucytosine cellular uptake and/or impairing flucytosine renal excretion. However, flucytosine can have synergistic effects when used with amphotericin B, and these two drugs frequently are used together to treat cryptococcal infections. This combination may allow for a reduction in the total daily dose of amphotericin B. However, amphotericin B-induced reductions in renal function can increase bone marrow toxicity from flucytosine.
Antimetabolites: (Minor) Flucytosine can cause significant hematologic toxicity. It should be used cautiously with all antineoplastic agents, especially those that cause bone marrow depression.
Carbamazepine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants, including carbamazepine.
Chlorpromazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Clozapine: (Moderate) Because of the ability of flucytosine to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants, including clozapine.
Codeine; Phenylephrine; Promethazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Codeine; Promethazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Cytarabine, ARA-C: (Major) Cytarabine, ARA-C can competitively inhibit flucytosine, antagonizing its antifungal activity.
Dichlorphenamide: (Moderate) Use dichlorphenamide and flucytosine together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including antifungals. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dichlorphenamide dose or discontinuing dichlorphenamide therapy.
Fluphenazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Ganciclovir: (Moderate) Use ganciclovir and flucytosine together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Hydroxyurea: (Minor) Flucytosine can cause significant hematologic toxicity. It should be used cautiously with all antineoplastic agents, especially those that cause bone marrow depression.
Lamivudine, 3TC; Zidovudine, ZDV: (Moderate) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression, such as flucytosine, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted.
Perphenazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Perphenazine; Amitriptyline: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Phenothiazines: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Porfimer: (Major) Avoid coadministration of porfimer with flucytosine due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like flucytosine may increase the risk of a photosensitivity reaction.
Prochlorperazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Promethazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Promethazine; Dextromethorphan: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Promethazine; Phenylephrine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Saccharomyces boulardii: (Major) Because Saccharomyces boulardii is an active yeast, it would be expected to be inactivated by any antifungals. The manufacturer does not recommend taking in conjunction with any antifungal agents. Patients should avoid use of this probiotic yeast until the fungal or yeast infection is completely treated.
Thioridazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Trifluoperazine: (Minor) Because of flucytosine's ability to cause significant hematologic toxicity, it should be used cautiously with all bone marrow depressants. These include: carbamazepine, clozapine, phenothiazines, zidovudine, ZDV and other blood dyscrasia-causing medications.
Valganciclovir: (Moderate) Use valganciclovir and flucytosine together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with flucytosine is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like flucytosine may increase the risk of a photosensitivity reaction.
Zidovudine, ZDV: (Moderate) Zidovudine, ZDV should be used cautiously with other drugs that can cause bone marrow suppression, such as flucytosine, because of the increased risk of hematologic toxicity. In some cases, a reduction in the dosage of zidovudine may be warranted.

Ancobon/Flucytosine Oral Cap: 250mg, 500mg

150 mg/kg/day PO.

150 mg/kg/day PO.

Safety and efficacy have not been established; however, doses of 150 mg/kg/day PO have been used off-label.

Safety and efficacy have not been established; however, doses of 150 mg/kg/day PO have been used off-label.

Safety and efficacy have not been established; however, doses of 150 mg/kg/day PO have been used off-label.

Safety and efficacy have not been established. Doses up to 150 mg/kg/day PO are the most commonly reported maximum doses; however, up to 200 mg/kg/day PO has been used.

Flucytosine penetrates fungal cells, where it is deaminated to fluorouracil by the fungal enzyme cytosine deaminase. Mammalian cells do not convert flucytosine to fluorouracil. Acting as an antimetabolite, fluorouracil competes with uracil, interfering with pyrimidine metabolism and eventually disrupting both RNA and protein synthesis. Flucytosine may also be converted to fluorodeoxyuridylic acid, which inhibits the enzyme thymidylate synthase and disrupts DNA synthesis. Although flucytosine is metabolized to 5-fluorouracil, flucytosine itself does not possess antineoplastic activity.
 
Susceptible fungi readily deaminate flucytosine to its active component, 5-fluorouracil. Resistance develops rapidly, however, if flucytosine is used as a single agent. The mechanism of resistance can be loss of the permease necessary for cytosine transport or decreased activity of uridine monophosphate pyrophosphorylase or cytosine deaminase. Fungi that usually are susceptible include: Candida species, Cryptococcus neoformans, and Candida glabrata.

Flucytosine is administered orally. It is a small molecule with limited protein binding (2% to 4%); therefore, it has a large Vd (approaching that of total body water) and is widely distributed throughout the body. Flucytosine penetrates the blood-brain barrier, achieving therapeutic concentrations in cerebrospinal fluid. Flucytosine is not metabolized. While fungal cells convert flucytosine to fluorouracil intracellularly, only trace amounts of fluorouracil can be detected in the serum. Elimination is primarily renal. Over 90% of a dose is excreted by glomerular filtration as unchanged drug. The elimination half-life is a function of creatinine clearance; in most adults with normal renal function, it is around 2.5 to 4 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Flucytosine is rapidly and almost completely absorbed with a bioavailability between 78% to 89%. Peak concentrations are achieved approximately 1 to 2 hours after administration. After a single 2 g dose in normal adults, peak serum concentrations were 30 to 40 mcg/mL; however, mean concentrations of 70 to 80 mcg/mL were measured in adults receiving flucytosine 150 mg/kg/day in combination with amphotericin for 6 weeks.

Use flucytosine during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. In animal studies, flucytosine was shown to be teratogenic in rats. The rats were administered doses ranging from 0.051-times to 0.89-times the recommended human dose (RHD) during the first trimester (days 7 to 13 of gestation). Teratogenic effects observed in the offspring included vertebral fusions, cleft lip and palate, and micrognathia. Flucytosine was not teratogenic in rabbits receiving doses of 0.243-times RHD, nor were there any statistically significant increases in adverse events observed in mice receiving doses of 0.236-times RHD.

It is not known whether flucytosine is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from flucytosine, discontinue breast-feeding or discontinue flucytosine, taking into account the importance of the drug to the mother.