Amphotericin thrombocytopenia with

When 5-FC is prescribed alone to patients with normal renal function, skin rash, epigastric distress, diarrhea, and liver enzyme elevations can occur. When it is prescribed to patients with renal insufficiency or to patients receiving concurrent amphotericin B therapy, blood levels of 5-FC may rise, and bone marrow toxicity leading to leukopenia and thrombocytopenia is common. 5-FC serum levels should be closely monitored in patients with renal insufficiency. Because of baseline leukopenia, 5-FC is often not tolerated by end-stage HIV-infected patients with disseminated fungal infection. 

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). 

Bone marrow suppression is a recognized toxic effect of flucytosine anemia, leukopenia, and thrombocytopenia occur in about 5% of cases. The hematological effects are dose-related and occur after prolonged high blood concentrations of flucytosine (over 100 pg/ml). Hematotoxicity is seen more often in the presence of renal insufficiency and hence during the use of flucytosine in combination with amphotericin. If bone marrow reserve has already been depleted by underlying disease or by medications, the risk of hematotoxicity increases. 

Flucytosine generally is associated with very few side effects in patients with normal renal, GI, and hematologic function, although rash, GI discomfort, diarrhea (5% to 10%), and reversible elevations in hepatic enzymes are observed occasionally. In patients with renal dysfunction or concomitant amphotericin B therapy, leukopenia, thrombocytopenia, and (rarely) enterocolitis may occur. Although studies have suggested that little or no conversion of flucytosine to fluorouracil occurs in vitro, serum concentrations of greater than 1000 ng/mL (therapeutic for the treatment of malignancies) have been... 

Experimental studies suggested that amphotericin B was less nephrotoxic when administered as a lipid formulation. However, this was not seen in dogs given amphotericin B in a fat emulsion. Amphotericin B is now routinely supplied and administered as a lipid formulation and this does appear to reduce its nephrotoxicity, but other adverse events, including hepatotoxicity, anaemia and thrombocytopenia may occur, albeit with low frequencies. ... 

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