Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans

Wakeham, Katie, Parkes-Ratanshi, Rosalind, Watson, Victoria, Ggayi, Abu-Baker, Khoo, Saye and Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200 (2010) 'Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans'. Journal of Antimicrobial Chemotherapy, Vol 65, Issue 2, pp. 316-319.

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Abstract

Background: Data from retrospective studies have suggested that there may be an interaction between fluconazole
and nevirapine, increasing nevirapine concentrations and potentially leading to hepatotoxicity.

Methods: 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.

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) (P¼0.009) 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, P¼0.012]. Fluconazole increased the nevirapine area under the curve
(AUC) from 0 to 8 h by 29% [geometric mean AUC0–8 46135 (95% CI 42432–57173) versus 35871
(95% CI 32808–41372) ng.h/mL, P¼0.016]. In the larger cohort from which the participants were drawn,
co-administration of fluconazole did not increase the risk of hepatotoxicity.

Conclusions: Fluconazole led to significant increases in nevirapine exposure, but was not associated with
evidence of increased hepatotoxicity

Item Type:	Article
Additional Information:	© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This work was originally published in the "Journal of Antimicrobial Chemotherapy" (2010), 65, 316-319.
Uncontrolled Keywords:	Uganda, pharmacokinetics, drug interactions, antiretroviral therapy
Subjects:	WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.2 Therapy
Digital Object Identifer (DOI):	https://doi.org/10.1093/jac/dkp451
Depositing User:	Users 43 not found.
Date Deposited:	07 Apr 2010 15:55
Last Modified:	22 Feb 2018 15:57
URI:	https://archive.lstmed.ac.uk/id/eprint/957

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