AEGiS-15IAC: The effect of fluconazole on nevirapine pharmacokinetics.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

The effect of fluconazole on nevirapine pharmacokinetics.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1239)

Pitt J, Orrell CJ, Geel J, Van Dyk M, Wood R
Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa

OBJECTIVE: With the widespread use of nevirapine as first line therapy in antiretroviral access programmes, it is becoming more important to understand the interactions between this drug and other medications commonly used in the treatment of HIV positive individuals. One such interaction is that between nevirapine and fluconazole. This study assessed the effects of nevirapine on the steady-state pharmacokinetics of fluconazole and that of fluconazole on nevirapine steady state pharmacokinetics.

METHODS: A single-center, open-label, single-arm trial of pharmacokinetic parameters of fluconazole alone and in combination with nevirapine in 24 patients on a stable regimen of three nucleoside analogue antiretrovirals.

RESULTS: The nevirapine effect on fluconazole pharmacokinetic parameters is minimal. However, the clearance of nevirapine was halved during concomitant administration of fluconazole resulting in an approximate doubling of nevirapine Cmin, Cmax and AUC. 95% of drug-related adverse events occurred during the period of co-administration of nevirapine and fluconazole. During this phase 25% (CI 7-43%) of patients developed serious hepatotoxicity including two cases of clinical hepatitis (8.3%) and four cases of transient grade 4 transaminase elevation (16.7%).

DISCUSSION: Nevirapine did not significantly influence the plasma levels of fluconazole, however fluconazole co-administration was associated with a doubling of nevirapine levels. The incidence of serious hepatotoxicity with the combination (25.0%) was much higher than reported in other studies using nevirapine alone (2.5% at 4 weeks). Conclusion Because of the pharmacokinetic interaction and apparent increased incidence of hepatotoxicity, the combination of nevirapine and fluconazole should be used with caution. Monitoring of liver functions tests is advisable.

Keywords: AEGIS, Nevirapine, Fluconazole, Area Under Curve, Drug Interactions, Therapeutic Equivalency, Incidence, Pharmaceutical Preparations, Humans, pharmacokinetics

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WeOrB1239