DOSING AND ADMINISTRATION OF ANTIFUNGALS USED IN CHILDREN

George R Thompson, III, MD: I think that’s been a big advance. We’ve started to worry about long-term problems from our treatment and obviously mortality is what we’re always concerned about. But with improvements in treatment, improvements in drug efficacy, we’re finally able to worry about some of these long-term complications and have a much broader and bigger picture view of the health of these patients affected with invasive fungal disease. As I mentioned previously, the three triazoles are available and will be used for invasive aspergillosis. But I know pediatrics has a very different treatment approach in how we look at these three different drugs. And we’ve talked a lot about safety, about the differences in TDM monitoring, but if you just think through the three drugs—voriconazole, posaconazole and isavuconazole—what can you tell me about available formulations and their dosing?

Antonio Arrieta, MD: This is summarized in Table 5.

Voriconazole

With voriconazole, we use very high doses. If we are going to go to oral voriconazole, we start with 200 mg BID, independent of the weight of the child. So, often, you end up using 14, 15 mg/kg per dose twice a day. And then we do TDM and follow safety. If you’re going to start IV, you go to 9 mg/kg. So, it is very aggressive dosing until about 13 years of age when you start seeing more of an adult PK profile and you start getting concerned about the rapidly increasing levels when you hit that mark. So, this dosing is very tricky, and TDM is indispensable not only because you want to make sure you have the appropriate level, but also because very often your patients’ levels change over time. You may have a trough level of 1.5 mg/L, and 3 weeks later you have undetectable voriconazole levels. So, it’s a very tricky drug to use, and I would strongly suggest that it always be used with an infectious diseases doctor supporting you.1,38,39

Table 5: Details about the pharmacology and dosing for mold-active triazole antifungal agents.1,38-41

DDI = drug-to-drug interaction; DR = delayed release; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; HSCT = hematopoietic stem cell transplantation; IA = invasive aspergillosis; IV = intravenous; MIC = minimum inhibitory concentration; PFS = powder for oral suspension; PK = pharmacokinetic; yo = years old.

Posaconazole

Posaconazole also has tricky pharmacokinetics. There are different formulations. The oral suspension has been left aside because it is so tricky. Fatty meals needed to be utilized; posaconazole has very great variability in bioavailability. So we are not using the suspension. There is the IV formulation, and there is the powder for oral suspension that has a very similar pharmacokinetic profile to the extended-release oral capsule.1,40 The dosing recently evaluated in the pediatric aspergillosis study is shown in Table 5.

Isavuconazole

We have been able to show consistently that there really is no significant difference between IV or oral, which is very reassuring. It allows the kids to go home. There are a variety of dosing options. It has very small (74.5 mg) capsules that can be used after 6 years of age. So, it has the IV formulation and the two different dosed capsules (74.5 mg and 186 mg, the small capsules and the larger capsules). It has very dependable, very consistent pharmacokinetics and pharmacodynamics.28 The on-label dosing is shown in Table 5. In my practice, I am very aggressive with the dosing.

TABLE OF CONTENTS

Faculty

George R. Thompson, III, MD

Professor of Medicine
University of California, Davis, School of Medicine
Sacramento, California

Antonio C. Arrieta, MD

Division Chief
Pediatric Infectious Diseases
Children’s Hospital of Orange County (CHOC)
Orange, California

MyCARE thanks Astellas for sponsoring this activity.

Copyright © 2025. ALL RIGHTS RESERVED. MyCARE Foundation. Astellas-sponsored, MA-MM-14973. May 2025. ASTELLAS and the Flying Star Logo are registered trademarks of Astellas Pharma Inc. Used with permission.