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Higher doses of antifungal agents needed to effectively treat children
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SAN DIEGO — Children generally require higher doses of antifungal agents than adults to provide clearance of infection, according to a presenter here at ID Week 2012.
William J. Steinbach, MD, who is associate professor of pediatrics, molecular genetics and microbiology at Duke University, Durham, N.C., said contrary to earlier dogma, newer pharmacokinetic studies of the four newest antifungal agents suggest that, generally, the younger the child, the higher the dose.
William J. Steinbach
Steinbach provided an overview of four of the newer primary antifungal agents used to treat children: voriconazole (Vfend, Pfizer), posaconazole (Noxafil, Merck), caspofungin (Cancidas, Merck) and micafungin (Mycamine, Astellas). Within the antifungal classes, there is likely little variance in the effectiveness of each drug, as the echinocandins (caspofungin and micafungin) are generally equivalent in efficacy to each other and the triazoles (posaconazole and voriconazole) also have a generally similar spectrum of activity, Steinbach said. However, there is some variation in conditions for administration, and each patient must be treated carefully. For example, there is high interpatient variability related to adequate dosing, especially with voriconazole.
“In pediatrics, dosing correctly is paramount. It is a spectrum of ages and doses and it’s not really only age that affects the pharmacokinetics,” Steinbach said during his presentation.
In addition, he said, voriconazole should not be taken with food.
“Make sure your patients are taking the drug the correct way, which for voriconazole is different that with posaconazole. Taking voriconazole with food will drop the bioavailability, which is already very poor in children, unlike in adult patients” he said.
In addition, pharmacokinetic studies have shown that the oral area under the curve (AUC) is lower than the IV AUC for voriconazole, he said, adding that voriconazole is easy to use incorrectly and complicated to use correctly.
Steinbach, who is also director of the International Pediatric Fungal Network, stressed the importance of getting trough levels with voriconazole: “When monitoring patients on oral voriconazole, make sure you are getting true trough levels, maybe half an hour before the next dose.”
Similar to voriconazole, posaconazole also likely requires a higher dose in children. However, an important difference is that posaconazole must be taken with food, Steinbach said.
Something new on the horizon for posaconazole is that a tablet should be commercially available within the next 2 years, in addition to an IV formulation. This may help with finding better dosing for children because, currently, the optimal dose in children is still rather unknown and being studied.
Regarding caspofungin, the concentrations of this drug are also different in younger children compared with adolescents. However, neonates, specifically, require a different and smaller dose than younger children.
Age is particularly important when using micafungin because the clearance seems to change, Steinbach said. Starting at about age 8 years, a patient can likely be given the adult dose, but it is not exactly that simple.
“With antifungals, it’s complicated to look at your young patient and understand how the PK changes,” he said. “The biggest mistake we see in antifungal use in children is the dosing.”
IDWeek 2012 is the first joint meeting of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, the Society for Healthcare Epidemiologists of America, and the HIV Medical Association.
For more information:
Steinbach WJ. Symposium #26. Presented at: ID Week 2012; Oct. 17-21, 2012; San Diego.
Disclosure: Steinbach serves as a scientific adviser and receives research grant funding from Astellas and Merck and serves on the speakers’ bureau and receives speaker honorarium from Pfizer.