II. Indications

  1. Systemic Fungal Infections (used with Amphotericin; risk of induced resistance when used alone)
    1. Cryptococcal Meningitis
    2. CNS Candidiasis (HIV Infection)
    3. Candida Pyelonephritis

III. Mechanism

  1. Flucytosine is a Fluorouracil prodrug, a fluorinated cytosine analog with Antifungal activity
  2. Within fungal cells, Flucytosine is deaminated to the active metabolite 5-Fluorouracil
    1. 5-Fluorouracil substitutes for the Pyrimidine uracil during RNA synthesis
    2. Inhibits fungal Protein synthesis
  3. Fluorouracil is also metabolized to the active 5-Fluorodeoxyuridine monophosphate (FdUMP)
    1. FdUMP inhibits thymidylate synthetase
    2. Blocks Nucleotide metabolism, and secondarily DNA synthesis and Protein synthesis

IV. Medications

  1. Capsules: 250 mg, 500 mg

V. Dosing

  1. Typically combined with Amphotericin
    1. Induced resistance may occur rapidly when Flucytosine is used alone
  2. Dose: 100 mg/kg/day orally divided four times daily for >=14 days
    1. Although not FDA approved in children, it is used off-label (not in renal dysfunction)
    2. Decrease dose to 75 mg/kg/day in weight <2 kg or age <60 days
  3. Renal Dosing: Adults
    1. Creatinine Clearance 20 to 40 ml/min: Take 25 mg/kg every 12 hours
    2. Creatinine Clearance 10 to 20 ml/min: Take 25 mg/kg every 24 hours
    3. Creatinine Clearance <10 ml/min: Take 25 mg/kg every 48 hours
    4. Hemodialysis: 25 to 50 mg/kg every 48 to 72 hours (dosing after Hemodialysis run)

VI. Adverse Effects

  1. Induced resistance
  2. Myelosuppression (Bone Marrow toxicity)
  3. Colitis
  4. Hepatotoxicity
  5. Nausea
    1. Spread capsule doses out over 15 minutes

VII. Safety

  1. Avoid in pregnancy (although listed as Pregnancy Category C)
  2. Avoid in Lactation

VIII. Pharmacokinetics

  1. Target peak level (2 hours after dose): 30 to 90 mcg/ml
    1. Drug levels >100 mcg/ml risk increased toxicity

IX. Monitoring

  1. Therapeutic drug levels (see Pharmacokinetics above)
  2. Liver function
  3. Hematologic labs
  4. Renal Function

XI. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (2012) Med Lett Drugs Ther 10(120): 61-8 [PubMed]

Images: Related links to external sites (from Bing)

Related Studies

Ontology: Flucytosine (C0016278)

Definition (NCI_NCI-GLOSS) A drug that treats infections caused by fungi.
Definition (NCI) A pyrimidine compound and a fluorinated cytosine analog exhibiting antifungal activity. After penetration into the fungal cells, flucytosine is deaminated to its active metabolite 5-fluorouracil. 5-fluorouracil replaces uracil during fungal RNA synthesis, thereby inhibiting fungal protein synthesis. In addition, fluorouracil is further metabolized to 5-fluorodeoxyuridylic acid monophosphate, which inhibits thymidylate synthetase, thereby interrupting nucleotide metabolism, DNA synthesis and ultimately protein synthesis.
Definition (MSH) A fluorinated cytosine analog that is used as an antifungal agent.
Definition (CSP) fluorinated cytosine analog that is used as an antifungal agent.
Definition (PDQ) A pyrimidine compound and a fluorinated cytosine analog exhibiting antifungal activity. After penetration into the fungal cells, flucytosine is deaminated to its active metabolite 5-fluorouracil. 5-fluorouracil replaces uracil during fungal RNA synthesis, thereby inhibiting fungal protein synthesis. In addition, fluorouracil is further metabolized to 5-fluorodeoxyuridylic acid monophosphate, which inhibits thymidylate synthetase, thereby interrupting nucleotide metabolism, DNA synthesis and ultimately protein synthesis. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41023&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41023&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C501" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Nucleic Acid, Nucleoside, or Nucleotide (T114)
MSH D005437
SnomedCT 28506006, 387155003
LNC LP14376-5, MTHU027149
English 5-Fluorocytosine, Flucytosine, 2(1H)-Pyrimidinone, 4-amino-5-fluoro-, 4-Amino-5-fluoro-2(1H)-pyrimidinone, flucytosine, 5FC, FLUOROCYTOSINE 05, fluorocytosine, flucytosine (medication), Flucytosine [Chemical/Ingredient], 5-fc, FLUCYTOSINE, 5-FC, Flucytosine (product), Flucytosine (substance)
Swedish Flucytosin
Czech flucytosin, 5-fluorocytosin
Finnish Flusytosiini
Russian 5-FTORTSITOZIN, FLUTSITOZIN, 5-ФТОРЦИТОЗИН, ФЛУЦИТОЗИН
Italian 5-Fluorocitosina, Flucitosina
German FLUORCYTOSIN 05, 5-Fluorcytosin, Flucytosin
Polish Ancobon, 5-fluorocytozyna, Flucytozyna
Japanese 5-フルオロシトシン, 5-フルオロサイトシン, フルシトシン
Portuguese 5-Fluorocitosina, Flucitosina, 5-Fluorcitosina
Spanish 5-fluorcitosina (sustancia), 5-fluorcitosina, 5-fluorocitosina, flucitosina (producto), flucitosina (sustancia), flucitosina, 5-Fluorocitosina, Flucitosina
French Flucytosine