Nevirapine + Fluconazole = Precautionary

Effect on Concentration

Nevirapine
Increase
Applies within class?
No
Fluconazole
No change
Applies within class?
No

Pharmacologic Effects

Nevirapine
Effect
N/A
Applies within class?
No
Fluconazole
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 30-Jul-2018

Summary

Sources

Nevirapine versus Fluconazole ^

Study Design

This study was nested within a large double-blind placebo-controlled study designed to determine if primary prophylaxis with fluconazole (200 mg three times per week) could reduce cryptococcal disease [CRYPTOPRO (ISRCTN 76481529)] in HIV-infected adults in rural south-western Uganda. Detailed pharmacokinetic studies were performed on 49 participants (22 on placebo and 27 on fluconazole) who had been on fluconazole or placebo with nevirapine for ≥4 weeks.

Study Results

The geometric mean pre-dose concentrations of nevirapine were 3865 ng/mL [95% confidence interval (95% CI) 3452–4758 ng/mL] and 5141 ng/mL (95% CI 4760–6595 ng/mL) (P = 0.009) in the placebo and fluconazole arms, respectively. The change in the peak nevirapine concentration in plasma (Cmax) was also higher in the fluconazole arm compared with the placebo arm [median 6546 (95% CI 6040–7974) versus 5126 (95% CI 4739–5773) ng/mL, P = 0.012]. Fluconazole increased the nevirapine area under the curve (AUC) from 0 to 8 h by 29% [geometric mean AUC0–8 46 135 (95% CI 42 432–57 173) versus 35 871 (95% CI 32 808–41 372) ng·h/mL, P = 0.016]. In the larger cohort from which the participants were drawn, co-administration of fluconazole did not increase the risk of hepatotoxicity.

Study Conclusions

Fluconazole led to significant increases in nevirapine exposure, but was not associated with evidence of increased hepatotoxicity. No dose adjustments are recommended.

References

Wakeham K, Parkes-Ratanshi R, Watson V, Ggavi AB, Khoo S, Lalloo DG. Co-administration of fluconazole increases nevirapine concentrations in hiv-infected ugandans. Journal Of Antimicrobial Chemotherapy, . 2009; 2: 316-319.