Flucytosine dosage

V. Cavrini, D. Bonazzi, and A. M. DiPietia, Analysis of flucytosine dosage forms by derivative UV spectioscopy and LC, J. Pharm. Biomed. Anal., 9 401 (1991). 

The dosage of flucytosine is 150—200 mg/kg orally in four portions every six hours. A 1% flucytosine solution has been developed for intravenous adrninistration. In some countries, a 10% ointment is also available. In patients with normal renal function, flucytosine is seldom toxic, but occasionally severe toxicity may be observed (leukopenia and thrombocytopenia). Plasma levels should be determined and the dose in patients with impaired renal function should be checked. Liver function tests (transaininases and alkaline phosphatase) should be performed regularly. In some patients with high flucytosine plasma levels, hepatic disorders have been observed (24). 

Zidovudine should be used cautiously with any other agent that causes bone marrow suppression, such as interferon-a, trimethoprim-sulfamethoxazole, dap-sone, foscarnet, flucytosine, ganciclovir, and valganci-clovir. Probenecid and interferon-p inhibit the elimination of zidovudine therefore, a dosage reduction of zidovudine is necessary when the drugs are administered concurrently. Ribavirin inhibits the phosphorylation reactions that activate zidovudine, and zidovudine similarly inhibits the activation of stavudine thus, the coadministration of zidovudine with ribavirin or stavudine is contraindicated. 

Flucytosine is currently available in North America only in an oral formulation. The dosage is 100-150 mg/kg/d in patients with normal renal function. It is well absorbed (> 90%), with serum concentrations peaking 1-2 hours after an oral dose. It is poorly protein-bound and penetrates well into all body fluid compartments, including the cerebrospinal fluid. It is eliminated by glomerular filtration with a half-life of 3-4 hours and is removed by hemodialysis. Levels rise rapidly with renal impairment and can lead to toxicity. Toxicity is more likely to occur in AIDS patients and those with renal insufficiency. Peak serum concentrations should be measured periodically in patients with renal insufficiency and maintained between 50 and 100 mcg/mL. 

To decrease dose-related toxicity by using reduced doses of one or more components of the drug regimen. The use of flucytosine in combination with amphotericin for the treatment of cryptococcal meningitis in non-HIV-infected patients allows for a reduction in amphotericin dosage with decreased amphotericin -induced nephrotoxicity. 

Flucytosine (also known as 5-flucytosine or 5-FC) is a fluorinated pyrimidine analogue that is highly water-soluble. Patients with creatinine clearances of less than 40 mL/min should receive 100-150 mg/kg daily in four divided doses. The dosage should be reduced by 50% in patients with a creatinine clearance of 25-50 mL/min and by 75% in patients with a clearance of 13-25 mL/min. Peak serum concentrations (2 hours after an oral dose) should be monitored in aU patients (particularly those with a creatinine clearance of less than 10 mL/min) to maintain peak serum concentrations of more than 100 mg/L.2 -29... 

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