Disclaimer to the On-line Edition
This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.
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- used primarily with amphotericin B for the treatment of severe infections caused by susceptible yeast; these 2 drugs act synergistically on some strains
- flucytosine is metabolized (primarily in fungal cells) to fluorouracil; fluorouracil competes with naturally occurring uracil and ultimately interferes with fungal RNA and protein synthesis
- flucytosine is well absorbed from the GI tract (approx. 75 to 90%); food decreases the rate, but not the extent of absorption
- widely distributed into body fluids and tissues
- 75 to 90% of an oral dose of flucytosine is eliminated unchanged in the urine, where concentrations are several times higher than in the blood; accordingly, dose and/or frequency must be adjusted in patients with impaired renal function
- it has been recommended that serum levels of flucytosine be monitored, especially since its elimination may be impaired by amphotericin B
- steady state serum flucytosine levels should be greater than 25 mcg/mL, to prevent the development of resistant strains and less than 100 mcg/mL to minimize toxicity (200 uL of blood are required for the assay)
- vomiting, diarrhea
- may cause bone marrow toxicity (associated with excessive serum levels)
- liver function should be monitored since enzyme elevations have been reported
- occasionally, skin rashes occur
- several references (84, 85, 104) suggest a dose of 12.5-37.5 mg/kg po q6h
- a recent paper(43) suggests a dose of 100 mg/kg po q24h; this regimen produced a median peak level of 83.9 mcg/mL in 4 infants
- we suggest an initial dose of 75 mg/kg po q 24h, and adjust this dose based on serum levels
- dosage must be adjusted in patients with impaired renal function
- serum levels should be monitored (see under Pharmacology)
- a pediatric suspension (10 mg/mL) can be prepared by the Department of Pharmacy
- an injectable solution (10 mg/mL) can also be prepared; this, however, is a long process which initially involves obtaining approval for use of the powder from the Health Protection Branch
- McEvoy G K (ed): AHFS Drug Information, American Society of Hospital Pharmacists, 1991.
- Baley JE, Meyers C, Kliegman AM et al: Pharmacokinetics, outcome of treatment, and toxic effects of amphotericin B and 5-fluorocytosine in neonates, J Pediatr 1990; 116: 791-7.
- Bhatt DR, Furman GI, Reber DJ et al: Neonatal Drug Formulary, 1990-1991, 2nd Edition, Fontana, California 92334.
- Taketomo CK, Hodding JH and Kraus DM: Pediatric Dosage Handbook, Lexi-Comp Inc., Cleveland, 1992.
- Young TE and Mangum OB: Neofax - A Manual of Drugs Used in Neonatal Care, Columbus, Ohio: Ross Laboratories, 1992.