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Meta-Analysis
. 2013 Jun;69(6):1211-21.
doi: 10.1007/s00228-012-1468-2. Epub 2013 Jan 17.

Safety of fluconazole in paediatrics: a systematic review

Oluwaseun Egunsola  1 , Abiodun Adefurin, Apostolos Fakis, Evelyne Jacqz-Aigrain, Imti Choonara, Helen Sammons
Affiliations
Meta-Analysis

Safety of fluconazole in paediatrics: a systematic review

Oluwaseun Egunsola et al. Eur J Clin Pharmacol. 2013 Jun.

Abstract

Purpose: To determine the safety of fluconazole in neonates and other paediatric age groups by identifying adverse events (AEs) and drug interactions associated with treatment.

Methods: A search of EMBASE (1950-January 2012), MEDLINE (1946-January 2012), the Cochrane database for systematic reviews and the Cumulative Index to Nursing and Allied Health Literature (1982-2012) for any clinical study about fluconazole use that involved at least one paediatric patient (≤17 years) was performed. Only articles with sufficient quality of safety reporting after patients' exposure to fluconazole were included.

Results: We identified 90 articles, reporting on 4,209 patients, which met our inclusion criteria. In total, 794 AEs from 35 studies were recorded, with hepatotoxicity accounting for 378 (47.6 %) of all AEs. When fluconazole was compared with placebo and other antifungals, the relative risk (RR) of hepatotoxicity was not statistically different [RR 1.36, 95 % confidence interval (CI) 0.87-2.14, P = 0.175 and RR 1.43, 95 % CI 0.67-3.03, P = 0.352, respectively]. Complete resolution of hepatoxicity was achieved by 84 % of patients with follow-up available. There was no statistical difference in the risk of gastrointestinal events of fluconazole compared with placebo and other antifungals (RR 0.81, 95 % CI 0.12-5.60, P = 0.831 and RR 1.23, 95 %CI 0.87-1.71, P = 0.235, respectively). There were 41 drug withdrawals, 17 (42 %) of which were due to elevated liver enzymes. Five reports of drug interactions occurred in children.

Conclusion: Fluconazole is relatively safe for paediatric patients. Hepatotoxicity and gastrointestinal toxicity are the most common adverse events. It is important to be aware that drug interactions with fluconazole can result in significant toxicity.

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Figures

Fig. 1
Fig. 1
Flow chart for articles included in the systematic review. CINAIL Cumulative Index to Nursing and Allied Health Literature, RCTs randomised controlled trials
Fig. 2
Fig. 2
a Fluconazole adverse effects (AEs) compared to those of other antifungals. b Fluconazole hepatotoxicity compared with that of placebo. c Fluconazole hepatotoxicity compared with that of nystatin
Fig. 2
Fig. 2
a Fluconazole adverse effects (AEs) compared to those of other antifungals. b Fluconazole hepatotoxicity compared with that of placebo. c Fluconazole hepatotoxicity compared with that of nystatin
See this image and copyright information in PMC

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