Interactions between the Anti-fungal Agent Voriconazole (Vfend) and Antiretroviral Drugs

Voriconazole Tablet

Voriconazole (Vfend) is an anti-fungal agent used to treat serious fungal infections. A member of class of anti-fungal medications called triazoles, it works by slowing the growth of the fungi that cause the debilitating infections.

Voriconazole is used to treat fungal infections such as invasive aspergillosis, a life-threatening fungal infection that begins in the lungs and can spread through the bloodstream to other organs. The presence of aspergillosis in HIV patients is an indication of severe immunosuppression.

In addition, the drug is used to treat esophageal candidiasis or thrush, an infection caused by a yeast-like fungus that can cause white patches and ulceration, which is also symptomatic of advancing disease in HIV positive patients.

In the current article, published in the May 2008 Annals of Pharmacotherapy, researchers summarized pertinent aspects of the available medical literature on interactions between voriconazole and various antiretroviral agents. These included the protease inhibitor ritonavir (Norvir), the non-nucleoside reverse transcriptase inhibitors (NNRTIs), the integrase inhibitor raltegravir (Isentress), and the CCR5 antagonist entry inhibitor maraviroc (Selzentry).

Results

Interactions between voriconazole and antiretroviral drugs are complex, according to the study authors. For example, they noted that voriconazole and ritonavir exhibit a time- and dose-dependent interaction. Ritonavir initially inhibits voriconazole metabolism, but with prolonged administration, subsequently induces voriconazole metabolism. This interaction is more pronounced with high doses of ritonavir, rather than the smaller dose used to boost other protease inhibitors.

Co-administration of voriconazole and the NNRTI efavirenz (Sustiva) at normal doses is contraindicated because of a two-way interaction resulting in efavirenz toxicity due to increased concentrations and decreased therapeutic effect of voriconazole due to decreased concentrations. If used together, dosage adjustments of both drugs are required.

Based on pharmacokinetic characteristics, interactions between voriconazole and other protease inhibitors, non-nucleoside reverse transcriptase inhibitors including the recently approved etravirine (Intelence), and maraviroc are likely, but have not been well characterized in the literature. Interactions between voriconazole and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or raltegravir are not anticipated.

In conclusion, the authors wrote, "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, they continued, "clinicians should be aware of the potential for interactions between voriconazole and antiretroviral agents and how to monitor for these interactions in clinical practice."

Regional Pharmacy Services, Capital Health Authority, Edmonton, Alberta, Canada.

4/25/08

Reference
EM Yakiwchuk, MM Foisy and CA Hughes. Complexity of Interactions Between Voriconazole and Antiretroviral Agents. Annals of Pharmacotherapy 42(5): 698-703. May 2008.