Hepatotoxicity fluconazole

Fluconazole (Diflucan) may be better absorbed and is possibly less hepatotoxic than ketoconazole, but it is considerably more expensive, an important consideration given the required length of therapy for most cutaneous fungal diseases. 

M.O. Gearhart, Worsening of liver function with fluconazole and review of azole antifungal hepatotoxicity, Ann. Pharmacother., 28, 1177, 1994. 

Adverse Effects. Hepatotoxicity is the most serious adverse effect of fluconazole this drug should be used cautiously in patients with impaired liver function. Other common side effects include headache and gastrointestinal disturbances (abdominal pain, nausea, vomiting). 

Fluconazole is one of the best tolerated antifungal drugs, with the most common complaint being gastrointestinal. Hepatotoxicity occurs only in a small number of patients. 

Second statement Itraconazole is less hepatotoxic than fluconazole. 

A chemotherapy patient developed severe pruritus and was given desloratadine and clemastine. Because of a pyrexia of unknown origin she was treated with meropenem and then 48 hours later fluconazole was added. After about 36 hours severe hepatotoxicity was detected, and apart from the anti-infectives the other drugs were stopped. Liver parameters recovered over the following week. Because the patient had previously reeeived clemastine and fluconazole without problems, this case was attributed to a possible interaction between fluconazole and desloratadine. ... 

Schottker B, Dosch A, Kraemer DM. Severe hepatotoxicity after application of desloratadine and fluconazole. Acta Haematol (Basel) (2003) 110, 43-44,... 

Nevirapine In a substudy within a large double-blind, randomized, placebo-con-trolled study of the use of fluconazole 200 mg three times per week in primary prophylaxis of cryptococcal disease in HIV-infected adults in rural south-western Uganda, fluconazole increased the nevirapine AUCo sh by 29% [42 ]. In the larger cohort from which the participants were drawn, co-administration of fluconazole did not increase the risk of hepatotoxicity, despite increased exposure to nevirapine. 

Observational studies Fluconazole is increasingly used to treat fungal infections in neonatal and paediatric populations. Common adverse reactions described include hepatotoxicity and gastrointestinal symptoms, but these two have not been thoroughly evaluated in neonates and other paediatric age groups. 

Based on an EMBASE and MEDLINE literature search, data from 90 studies in 4209 subjects were reviewed [13 ]. During the studies, 794 adverse effects were recorded. The most common adverse effect was fluconazole-related hepatotoxicity (47.6%), of which the majority occurred in neonates (295 out of 378 cases). Gastrointestinal symptoms including nausea, vomiting, abdominal pain, diarrhoea, dyspepsia, anorexia and gastritis accounted for 15.4% of all adverse effects. 

N. Somchit, A. R. Norshahida, A. H. Hasiah, A. Zuraini, M. R. Sulaiman and M. M. Noordin, Hepatotoxicity induced by antifungal drugs itraconazole and fluconazole in rats a comparative in vivo study. Hum. Exp. Toxicol, 2004, 23, 519-525. 

R. J. Rodriguez and D. Acosta, Comparison of ketoconazole- and fluconazole-induced hepatotoxicity in a primary culture system of rat hepatocytes. Toxicology, 1995, 96, 83-92. 

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