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Pharmacology of flucytosine (5-FC)

Richard H Drew, PharmD, MS, FCCP
John R Perfect, MD
Section Editor
Carol A Kauffman, MD
Deputy Editor
Anna R Thorner, MD


Flucytosine (5-flucytosine, 5-FC, Ancobon) is an antifungal agent originally developed in 1957 as an antimetabolite. Although it has found no role as an anti-tumor agent, it is used for the treatment of certain fungal infections.

Due to a high incidence of primary and/or acquired resistance, use of flucytosine as monotherapy is significantly restricted. Combination therapy of 5-FC with amphotericin B is recommended for the initial management of severe cryptococcal pneumonia and meningoencephalitis. Less frequently, 5-FC is added to the treatment of select invasive candidal infections.

Hematologic and hepatic toxicities may occur with 5-FC administration but can be reduced by monitoring serum concentrations and by adjusting the dose empirically in patients with renal dysfunction. When serum concentration testing is not available, careful monitoring for cytopenias will be necessary.

High acquisition costs associated with 5-FC worldwide (including the United States) have limited its availability. This is most notable in select African and Asian countries despite the high incidence of cryptococcal diseases in these areas [1-3].

The pharmacology of flucytosine will be discussed here. The clinical use of flucytosine is discussed separately. (See "Treatment of Cryptococcus neoformans meningoencephalitis in HIV-infected patients" and "Treatment of Cryptococcus neoformans meningoencephalitis and disseminated infection in HIV seronegative patients" and "Candida endocarditis and suppurative thrombophlebitis" and "Candida infections of the central nervous system".)


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Literature review current through: Sep 2016. | This topic last updated: Jan 5, 2016.
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  1. Govender NP, Meintjes G, Banoo S. Access to flucytosine for HIV-infected patients with cryptococcal meningitis – an urgent need. S Afr Med J 2014; 104:594.
  2. Loyse A, Dromer F, Day J, et al. Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal. J Antimicrob Chemother 2013; 68:2435.
  3. Loyse A, Thangaraj H, Easterbrook P, et al. Cryptococcal meningitis: improving access to essential antifungal medicines in resource-poor countries. Lancet Infect Dis 2013; 13:629.
  4. Polak A, Scholer HJ. Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy 1975; 21:113.
  5. Vermes A, Guchelaar HJ, Dankert J. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother 2000; 46:171.
  6. Dodds ES, Drew RH, Perfect JR. Antifungal pharmacodynamics: review of the literature and clinical applications. Pharmacotherapy 2000; 20:1335.
  7. Andes D, van Ogtrop M. In vivo characterization of the pharmacodynamics of flucytosine in a neutropenic murine disseminated candidiasis model. Antimicrob Agents Chemother 2000; 44:938.
  8. Vanden Bossche H, Dromer F, Improvisi I, et al. Antifungal drug resistance in pathogenic fungi. Med Mycol 1998; 36 Suppl 1:119.
  9. Charlier C, El Sissy C, Bachelier-Bassi S, et al. Acquired Flucytosine Resistance during Combination Therapy with Caspofungin and Flucytosine for Candida glabrata Cystitis. Antimicrob Agents Chemother 2016; 60:662.
  10. Chin CS, Cheong YM, Wong YH. 5-Fluorocytosine resistance in clinical isolates of Cryptococcus neoformans. Med J Malaysia 1989; 44:194.
  11. Shadomy HJ, Wood-Helie S, Shadomy S, et al. Biochemical serogrouping of clinical isolates of Cryptococcus neoformans. Diagn Microbiol Infect Dis 1987; 6:131.
  12. Franzot SP, Hamdan JS. In vitro susceptibilities of clinical and environmental isolates of Cryptococcus neoformans to five antifungal drugs. Antimicrob Agents Chemother 1996; 40:822.
  13. Bava AJ, Negroni R. [In vitro susceptibility of Cryptococcus strains to 5 antifungal drugs]. Rev Inst Med Trop Sao Paulo 1989; 31:346.
  14. Pujol C, Pfaller MA, Soll DR. Flucytosine resistance is restricted to a single genetic clade of Candida albicans. Antimicrob Agents Chemother 2004; 48:262.
  15. Pfaller MA, Messer SA, Boyken L, et al. In vitro activities of 5-fluorocytosine against 8,803 clinical isolates of Candida spp.: global assessment of primary resistance using National Committee for Clinical Laboratory Standards susceptibility testing methods. Antimicrob Agents Chemother 2002; 46:3518.
  16. Pfaller MA, Diekema DJ, Gibbs DL, et al. Candida krusei, a multidrug-resistant opportunistic fungal pathogen: geographic and temporal trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005. J Clin Microbiol 2008; 46:515.
  17. Desnos-Ollivier M, Bretagne S, Bernède C, et al. Clonal population of flucytosine-resistant Candida tropicalis from blood cultures, Paris, France. Emerg Infect Dis 2008; 14:557.
  18. Montgomerie JZ, Edwards JE Jr, Guze LB. Synergism of amphotericin B and 5-fluorocytosine for candida species. J Infect Dis 1975; 132:82.
  19. Gomez-Lopez A, Mellado E, Rodriguez-Tudela JL, Cuenca-Estrella M. Susceptibility profile of 29 clinical isolates of Rhodotorula spp. and literature review. J Antimicrob Chemother 2005; 55:312.
  20. Diekema DJ, Petroelje B, Messer SA, et al. Activities of available and investigational antifungal agents against rhodotorula species. J Clin Microbiol 2005; 43:476.
  21. Brouwer AE, van Kan HJ, Johnson E, et al. Oral versus intravenous flucytosine in patients with human immunodeficiency virus-associated cryptococcal meningitis. Antimicrob Agents Chemother 2007; 51:1038.
  22. Daneshmend TK, Warnock DW. Clinical pharmacokinetics of systemic antifungal drugs. Clin Pharmacokinet 1983; 8:17.
  23. Soltani M, Tobin CM, Bowker KE, et al. Evidence of excessive concentrations of 5-flucytosine in children aged below 12 years: a 12-year review of serum concentrations from a UK clinical assay reference laboratory. Int J Antimicrob Agents 2006; 28:574.
  24. DHHS Panel on Opportunistic Infections (OI) in HIV-Infected Adults and Adolescents, Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), May 7, 2013. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on October 24, 2014).
  25. Kunka ME, Cady EA, Woo HC, Thompson Bastin ML. Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy. Case Rep Crit Care 2015; 2015:927496.
  26. Goodwin ML, Drew RH. Antifungal serum concentration monitoring: an update. J Antimicrob Chemother 2008; 61:17.
  27. Andes D, Pascual A, Marchetti O. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob Agents Chemother 2009; 53:24.
  28. Vermes A, van Der Sijs H, Guchelaar HJ. Flucytosine: correlation between toxicity and pharmacokinetic parameters. Chemotherapy 2000; 46:86.
  29. Perfect JR, Dismukes WE, Dromer F, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis 2010; 50:291.
  30. Vermes A, Guchelaar HJ, van Kuilenburg AB, Dankert J. 5-fluorocytosine-related bone-marrow depression and conversion to fluorouracil: a pilot study. Fundam Clin Pharmacol 2002; 16:39.
  31. Vermes A, Guchelaar HJ, Dankert J. Prediction of flucytosine-induced thrombocytopenia using creatinine clearance. Chemotherapy 2000; 46:335.
  32. South Africa. Supreme Court, Cape Provincial Division. Castell v. De Greef. S Afr Law Rep 1994; 1994:408.