In the JournalsPerspective

Noxafil use up by more than 20% per year in hospitalized children

Photo of Kevin J. Downes
Kevin J. Downes

Noxafil use in hospitalized children increased significantly over a 10-year period, according to a study published in the Journal of the Pediatric Infectious Diseases Society. Most children who received the drug were aged younger than 13 years, researchers said.

Noxafil (posaconazole, Merck), a second-generation triazole with antifungal activity against yeasts and molds, is approved as prophylaxis against invasive Aspergillus and Candida species infections in severely immunocompromised patients aged 13 years and older. The drug is also used to treat oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.

“We performed a retrospective study of posaconazole administration in hospitalized children from October 2006 to September 2015 using data from the Pediatric Health Information System database,” Kevin J. Downes, MD, an attending physician in the division of infectious diseases at Children's Hospital of Philadelphia and an assistant professor of pediatrics at the University of Pennsylvania’s Perelman School of Medicine, told Infectious Diseases in Children. “Over the study period, there was significant variability in posaconazole utilization across hospitals, and overall use increased by 22% per year, including by 27% per year in children less than 13 years of age for whom the drug was not approved.”

Downes and colleagues used data from 49 children’s hospitals in the United States from 2006 — when the FDA first approved the use of posaconazole — to September 2015. The study included children aged younger than 18 years who were prescribed the drug for at least 1 day.

The researchers reported 4,855,093 admissions, including 878 children who received posaconazole. Most of the children (53.8%) were aged younger than 13 years.

Downes and colleagues noted that although the prescribing rates of posaconazole increased significantly during the study period, the rates of other active mold-active azoles, including itraconazole and voriconazole, decreased or remained the same. The researchers reported there was significant variation in posaconazole use among the hospitals. They noted that 10 hospitals accounted for more than half of all posaconazole use, and those hospitals increased their use of the drug by 46% per year. Downes and colleagues noted that the wide variation in use might reflect differences in the needs of the patients served by those hospitals, including the number of immunocompromised children.

The researchers also noted that the increase in the off-label use of posaconazole in younger patients might be because of “a lack of other safe and effective options.”

Downes and colleagues wrote that clinical efficacy trials on posaconazole have demonstrated the superiority of the drug over fluconazole and itraconazole as prophylaxis in adolescents who were at high risk for invasive fungal disease.

“We believe that these findings are important given the increasing number of immunocompromised and immunosuppressed children in the United States, and that future research is needed to evaluate the efficacy, safety and dosing of posaconazole for the treatment of and prophylaxis against invasive fungal disease in children,” Downes said. – by Bruce Thiel

Disclosures: Downes reports that the study was supported in part by the Investigator-Initiated Studies Program of Merck, adding that the work is solely the product of the authors and the opinions expressed in the paper do not necessarily represent those of Merck. Downes also reports receiving research support from Merck and Pfizer, unrelated to the current work. Please see the study for the other authors’ relevant financial disclosures.

Photo of Kevin J. Downes
Kevin J. Downes

Noxafil use in hospitalized children increased significantly over a 10-year period, according to a study published in the Journal of the Pediatric Infectious Diseases Society. Most children who received the drug were aged younger than 13 years, researchers said.

Noxafil (posaconazole, Merck), a second-generation triazole with antifungal activity against yeasts and molds, is approved as prophylaxis against invasive Aspergillus and Candida species infections in severely immunocompromised patients aged 13 years and older. The drug is also used to treat oropharyngeal candidiasis refractory to itraconazole and/or fluconazole.

“We performed a retrospective study of posaconazole administration in hospitalized children from October 2006 to September 2015 using data from the Pediatric Health Information System database,” Kevin J. Downes, MD, an attending physician in the division of infectious diseases at Children's Hospital of Philadelphia and an assistant professor of pediatrics at the University of Pennsylvania’s Perelman School of Medicine, told Infectious Diseases in Children. “Over the study period, there was significant variability in posaconazole utilization across hospitals, and overall use increased by 22% per year, including by 27% per year in children less than 13 years of age for whom the drug was not approved.”

Downes and colleagues used data from 49 children’s hospitals in the United States from 2006 — when the FDA first approved the use of posaconazole — to September 2015. The study included children aged younger than 18 years who were prescribed the drug for at least 1 day.

The researchers reported 4,855,093 admissions, including 878 children who received posaconazole. Most of the children (53.8%) were aged younger than 13 years.

Downes and colleagues noted that although the prescribing rates of posaconazole increased significantly during the study period, the rates of other active mold-active azoles, including itraconazole and voriconazole, decreased or remained the same. The researchers reported there was significant variation in posaconazole use among the hospitals. They noted that 10 hospitals accounted for more than half of all posaconazole use, and those hospitals increased their use of the drug by 46% per year. Downes and colleagues noted that the wide variation in use might reflect differences in the needs of the patients served by those hospitals, including the number of immunocompromised children.

The researchers also noted that the increase in the off-label use of posaconazole in younger patients might be because of “a lack of other safe and effective options.”

Downes and colleagues wrote that clinical efficacy trials on posaconazole have demonstrated the superiority of the drug over fluconazole and itraconazole as prophylaxis in adolescents who were at high risk for invasive fungal disease.

“We believe that these findings are important given the increasing number of immunocompromised and immunosuppressed children in the United States, and that future research is needed to evaluate the efficacy, safety and dosing of posaconazole for the treatment of and prophylaxis against invasive fungal disease in children,” Downes said. – by Bruce Thiel

Disclosures: Downes reports that the study was supported in part by the Investigator-Initiated Studies Program of Merck, adding that the work is solely the product of the authors and the opinions expressed in the paper do not necessarily represent those of Merck. Downes also reports receiving research support from Merck and Pfizer, unrelated to the current work. Please see the study for the other authors’ relevant financial disclosures.

    Perspective
    David A. Kaufman

    David A. Kaufman

    This article highlights the growing use of a newer antifungal and the need for pharmacokinetic and efficacy studies in younger patients, including infants. Currently, we are extrapolating most dosing for children aged younger than 12 years. Posaconazole is of great interest because it can be given both enterally (oral suspension and tablet forms) and intravenously. The ability to give enterally translates into the facilities treating children as outpatients, and that significantly decreases the need for hospitalization, hospital days, costs and the need for and complications related to peripheral and central venous access. Additionally, similar to some other antifungals, there is the availability to obtain posaconazole levels.

    Investigators and clinicians are starting to hear the call for more studies. This year, one pediatric study by Boonsathorn and colleagues in Clinical Pharmacokinetics examined pharmacokinetics data from approximately 117 infants with a median age of 5.7 years — including 22 infants aged 6 months to 2 years, 47 young children aged 2 to 6 years and 36 children aged 7 to 12 years. They observed challenges with bioavailability in patients with diarrhea, patients on proton pump inhibitors and younger patients. Also, they did not study any infants aged younger than 6 months.

    This study highlights many of the posaconazole dosing questions in infants and children that remain unanswered.

    We need more studies to help us know the right dosing of posaconazole in infants and children to then evaluate its efficacy, so we can choose it and use it wisely.

    Reference:

    Boonsathorn S, et al. Clin Pharmacokinet. 2018;doi:10.1007/s40262-018-0658-1.

    • David A. Kaufman, MD, FAAP
    • Professor of pediatrics
      Division of neonatology, University of Virginia Children’s Hospital

    Disclosures: Kaufman reports no relevant financial disclosures.