Safety and pharmacokinetics of coadministered voriconazole and anidulafungin

There is considerable interest in combining echinocandin and triazole antifungal agents for treatment of invasive fungal infections; however, information is needed regarding the tolerability and potential for pharmacokinetic interactions. Anidulafungin is a semisynthetic echinocandin, and voriconazole is an extended-spectrum triazole. In a random sequence, 17 subjects received anidulafungin with placebo, voriconazole with placebo, and anidulafungin with voriconazole. Anidulafungin was administered intravenously: 200 mg on day 1, then 100 mg/d on days 2 through 4. Voriconazole was administered orally: 400 mg every 12 hours on day 1, then 200 mg every 12 hours on days 2 to 4. No dose-limiting toxicities or serious adverse events occurred, and all adverse events were mild and consistent with the known safety profiles of both drugs. Pharmacokinetic parameters were not affected by coadministration. The geometric mean ratio (90% confidence interval) of the combination/drug alone for AUC(SS) was 97.4% (94.9-99.9), 97.4% (92.1-103.0), and 94.4% (87.0-102.5) for anidulafungin, voriconazole, and the voriconazole metabolite, respectively.