Flucytosine adverse effects

B. Amphotericin B remains the drug of choice in the treatment of disseminated or invasive fungal infections in immunocompromised hosts bone marrow transplant recipients are the most heavily immunocompromised patients encountered in the hospital setting. 5-Flucytosine has no significant activity against Aspergillus spp., and it has bone marrow toxicity as a common adverse effect it should... 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Adverse Effects. Flucytosine may cause hepatotoxicity and may also impair bone marrow function, resulting in anemia, leukopenia, and several other blood dyscrasias.69 This drug may also produce severe gastrointestinal disturbances, including nausea, vomiting, diarrhea, and loss of appetite. 

FLUCYTOSINE ANTIVIRALS-ZIDOVUDINE Possibly t adverse effects with zidovudine Additive toxicity Avoid if possible otherwise monitor FBC and renal function (weekly). 1 doses as necessary... 

Flucytosine (5-fluorocytosine) is metabolised in the fungal cell to 5-fluorouracil which inhibits nucleic acid synthesis. It is weU absorbed from the gut, penetrates effectively into tissues and almost all is excreted unchanged in the urine (t) 4 h). The dose should be reduced for patients with impaired renal function, and the plasma concentration should be monitored. The drug is well tolerated when renal function is normal. Candida albicans rapidly becomes resistant to flucytosine which ought not to be used alone it may be combined with amphotericin (see Table 14.2) but this increases the risk of adverse effects (leucopenia, thrombocytopenia, enterocolitis) and it is reserved for serious infections where the risk-benefit balance is favourable (e.g. Cryptococcus neoformans meningitis). 

Nausea, vomiting, and diarrhea are the most common adverse effects of flucytosine. 

Adverse effects of flucytosine are gastrointestinal upset, anaemia, neutropenia, thrombocytopenia and alopecia, all mild and reversible. 

Zidovudine is rapidly absorbed from the G1 tract with peak serum concentrations occurring within 30 to 90 minutes. It binds to plasma proteins to the extent of 35 to 40%. Zidovudine is rapidly metabolized in the liver to the inactive 3 -azido-3 -deoxy-5 -0-beta-D-glucopyranuronosylthymi-dine (GAZT), which has an apparent elimination half-life of 1 hour. Zidovudine undergoes glomerular filtration and active tubular secretion. Coadministration of zidovudine with agents such as dapsone, pentamidine, amphotericin B, flucytosine, vincristine, vinblastine, adriamycin, and interferon with potential to cause nephrotoxicity or cytotoxicity to hematopoietic elements, enhance its risk of adverse effects. Probenecid will inhibit the renal excretion of zidovudine. 

The combined use of flucytosine and amphotericin B is more effective than flucytosine alone in the treatment of cryptococcal meningitis, as demonstrated in an early study, and is still the recommended treatment. However, amphotericin B can cause deterioration in renal function, which reduces flucytosine elimination, and may result in raised flucytosine blood levels. In addition, amphotericin may increase the cellular uptake of flucytosine. Whatever the exact mechanism, combined use increases flucytosine bone marrow toxicity. A study of 194 patients randomised to either a 4 or 6-week course of low-dose amphotericin B (initially 0.3 mg/kg daily) and maximal dose flucytosine (150 mg/kg daily, adjusted for renal function) found that severe adverse effects were common. These included azotaemia (51 patients), blood dyscrasias (52 patients), and hepatitis (13 patients). ... 

Combination studies In 41 HIV-positive patients with cryptococcal meningitis combination therapy with flucytosine -l-fluconazole was more effective than fluconazole alone, with fewer deaths however, more patients had grade 3 or 4 neutropenia with combination therapy, although there was no increase in infection-related adverse events [69 ]. 

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