Abstract
The purpose of this review is to examine the literature for reports of clinically significant interactions noted amongst HIV antiretroviral medications when coadministered with posaconazole. A literature search was conducted to identify studies addressing drug interactions between posaconazole and HIV antiretroviral medications. Two pharmacokinetic studies and three clinical trials involving the administration of posaconazole to HIV-infected patients were identified. The pharmacokinetic studies involved concomitant administration of either a protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI). Both studies showed alterations in systemic concentrations of either posaconazole or the HIV antiretroviral when administered together. Of the three clinical trials, all patients were on HIV antiretrovirals. However, their potential interaction with posaconazole was not explored. To date, there is no published literature regarding the interaction between maraviroc or elvitegravir and posaconazole. Dose adjustments for each are recommended when coadministered with strong CYP 3A4 inhibitors or inducers. Currently available literature points to the potential for clinically significant drug interactions when posaconazole is coadministered with HIV antiretrovirals, specifically NNRTIs and PIs. More studies are needed involving a wider range of HIV antiretrovirals to determine the significance of the interaction. Clinicians should be aware of this potentially significant interaction and avoid concomitant administration when possible. When available, consideration should be given to therapeutic drug monitoring of antiretroviral serum concentrations in select patients.
Highlights
Posaconazole is an extended spectrum triazole antifungal agent that is structurally similar to itraconazole
Krishna et al evaluated the pharmacokinetic interaction of posaconazole with atazanavir, with and without ritonavir, as well as the pharmacokinetic interaction of posaconazole with efavirenz in a phase I, open-label, randomized, 2-part, crossover study [34]
Based on the results of this two part study, the authors concluded that the potential for increased plasma concentrations of both protease inhibitor (PI) and nucleoside reverse transcriptase inhibitor (NNRTI) could occur when administered with posaconazole
Summary
Posaconazole is an extended spectrum triazole antifungal agent that is structurally similar to itraconazole It has received Food and Drug Administration (FDA) approval for use in the prophylaxis of invasive fungal infections, Aspergillus and Candida infections, in high risk immunocompromised patients who are 13 years or older. It is indicated for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole [1]. Posaconazole has fungicidal activity against Cryptococcus neoformans, Aspergillus species (i.e., A. fumigatus, A. flavus and A. terreus), Blastomyces dermatitidis, Trichosporon and specific Candida species (i.e., C. krusei, C. parapsilosis, C. lusitaniae and C. inconspicua). Posaconazole is recommended as an alternative treatment option for patients who cannot take fluconazole for oral candidiasis as well as an option for patients who have failed first-line treatment options for histoplasmosis and aspergillosis, though data in this patient population is lacking [7]
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