Complexity of Interactions Between Voriconazole and Antiretroviral Agents

Abstract

Objective: To evaluate and summarize pertinent aspects of the literature on interactions between voriconazole and antiretroviral agents. Data Sources: Primary literature was identified through MEDLINE (1950-February 2008), EMBASE (1988-February 2008), and International Pharmaceutical Abstracts (1970-February 2008) using the search terms voriconazole, ritonavir, protease inhibitors, nonnucleoside reverse transcriptase inhibitors, raltegravir, maraviroc, and drug interactions. Additionally, relevant abstracts from infectious diseases and HIV conferences (2004-February 2008), reference citations from relevant publications, and product information monographs were reviewed. Study Selection And Data Abstraction: All articles identified from the data sources and published in English were reviewed. Of these, studies and reports addressing voriconazole pharmacokinetics or interactions with antiretroviral agents were evaluated. Data Synthesis: The interactions between voriconazole and antiretroviral drugs are complex. Voriconazole and ritonavir exhibit a time- and dose-dependent interaction. Ritonavir initially inhibits voriconazole metabolism, but, with chronic administration, subsequently induces voriconazole metabolism. This interaction is more pronounced with high doses of ritonavir. Coadministration of voriconazole and efavirenz at usual doses is contraindicated because of a 2-way interaction resulting in efavirenz toxicity and decreased therapeutic effect of voriconazole. Dosage adjustments of both drugs are required. Based on pharmacokinetic characteristics, interactions between voriconazole and other protease inhibitors, nonnucleoside reverse transcriptase inhibitors (including etravirine), and maraviroc are likely but have not been well characterized in the literature. Interactions between voriconazole and nucleoside reverse transcriptase inhibitors or raltegravir are not anticipated. Conclusions: Interactions between voriconazole and antiretrovirals have the potential for serious consequences. However, because there is limited information available, further studies are warranted to establish these interactions and clarify their appropriate management. Until then, clinicians should be aware of the potential for interactions between voriconazole and antiretroviral agents and how to monitor for these interactions in clinical practice.