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Whereas fluconazole and itraconazole have been available for more than a decade, voriconazole and posaconazole have entered clinical practice only recently [25] (Fig.?2). Fluconazole.? With the exception of premature neonates, where clearance may be decreased during the first days of life, paediatric patients tend to have greater normalized plasma clearance and a shorter half-life than adults EPZ5676 price [36�C39] (Table?2). Therefore, relative to weight, higher dosages are required in children to achieve comparable exposures. In paediatric patients, at dosages of up to 12?mg/kg daily, fluconazole is generally well tolerated [40]. The most common reported side effects include gastrointestinal disturbances (8%), increases in hepatic transaminases (5%) and skin reactions (1%); toxicity-related LY2109761 clinical trial discontinuations occur in approximately 3% of patients [40]. Severe side effects, including relevant hepatotoxicity and exfoliative skin reactions, have been reported anecdotally [25]. Fluconazole may be used for invasive Candida infections caused by susceptible organisms in paediatric patients of all ages who are in a stable condition and who have not received prior azole therapy [22, 41�C47]. The recommended dosage range beyond the neonatal period is 6�C12?mg/kg daily; in view of the faster clearance rate and the absence of population pharmacokinetics, however, 12?mg/kg daily may be the most appropriate dosage. For infants, population-based pharmacokinetics and Monte Carlo simulation showed that for the treatment of invasive candidiasis, a dose of at least 12?mg/kg daily in the first 90?days after birth is needed to achieve an area under the concentration curve/MIC index >50 for Candida species with MIC?MAPK basis of these studies, fluconazole prophylaxis is a valid option for centres with a high frequency (>10%) of invasive Candida infections in premature infants of