Analyzing data from completed trials to determine the safety of fluconazole for prevention and treatment of candidiasis, a life-threatening fungal infection, in premature infants.
Summary
This study evaluated the safety of fluconazole for prophylaxis (prevention) and treatment of candidiasis in premature infants by analyzing data from four completed randomized trials over the course of nearly twenty years:
- Fluconazole Prophylaxis for the Prevention of Candidiasis in Infants < 750 Grams Birth Weight
- Pharmacokinetics of a Fluconazole Loading Dose in Infants and Toddlers
- Safety and Pharmacokinetics of Fluconazole in Children Supported by Extracorporeal Membrane Oxygenation (ECMO)
- A Multicenter, Open Label Pharmacokinetics Study of Fluconazole in Infants
Approximately 3,000 infants develop candidiasis, also known as yeast infections, each year, with most of the burden falling on infants born <28 weeks gestational age. Unfortunately, despite antifungal treatment, 20% of infants who develop neonatal candidiasis die as a result of the disease. Among survivors, morbidity—such as neurodevelopmental impairment—is substantial.
Fluconazole, an antifungal medicine, is often used for preventing and treating candidiasis in infants. However, the fluconazole label approved by the U.S. Food and Drug Administration (FDA) lacked information on safety and dosing for this group. With data from four studies, the PTN was able to inform an FDA update to the fluconazole label which includes information to help prescribe the medicine for premature and full-term infants.
Important additions to the fluconazole label include:
- Pharmacokinetic data on fluconazole in infants
- Suggestion of a loading dose for children
- Information on dosing for pediatric patients being supported with extracorporeal membrane oxygenation (ECMO)
- Information on the use of fluconazole for prevention of Candida infection in infants
View study data for fluconazole prophylaxis for prevention of candidiasis in infants, secondary analysis of data from prophylaxis study, safety/PK in children supported with extracorporeal membrane oxygenation, and PK of loading dose in infants and toddlers on NICHD's Data and Specimen Hub (DASH).
Publications
- Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 GramsAntimicrobial Agents and Chemotherapy • August 2016. Momper JD, Capparelli EV, Wade KC, Kantak A, Dhanireddy R, Cummings JJ, Nedrelow JH, Hudak ML, Mundakel GT, Natarajan G, Gao J, Laughon M, Smith PB, Benjamin DK Jr. Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize ...
- Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level DataClinical Infectious Diseases • August 2016. Ericson JE, Kaufman DA, Kicklighter SD, Bhatia J, Testoni D, Gao J, Smith PB, Prather KO, Benjamin DK Jr; Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated ...
- Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenationAntimicrobial Agents and Chemotherapy • June 2015. Watt KM, Gonzalez D, Benjamin DK Jr, Brouwer KL, Wade KC, Capparelli E, Barrett J, Cohen-Wolkowiez M. Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal ...
- Editorial commentary: Fluconazole therapeutic drug monitoring in children with cancer: not todayClinical Infectious Disease • December 2014. Cohen-Wolkowiez M, Benjamin DK Jr. This editorial focuses on insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children. Access article on PubMed.
- Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trialJAMA • June 2014. Benjamin DK Jr, Hudak ML, Duara S, Randolph DA, Bidegain M, Mundakel GT, Natarajan G, Burchfield DJ, White RD, Shattuck KE, Neu N, Bendel CM, Kim MR, Finer NN, Stewart DL, Arrieta AC, Wade KC, Kaufman DA, Manzoni P, Prather KO, Testoni D, Berezny KY, Smith PB; Fluconazole Prophylaxis Study Team. Invasive candidiasis in ...
Presentations
Pediatric Academic Societies Annual Meeting, April 25-28, 2015
Population Pharmacokinetics of Fluconazole in Extremely Low Birth Weight Infants
Momper JD, Capparelli EV, Wade KC, Natarajan G, Gao J, Laughon M, Smith PB, Benjamin DK Jr, on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network
OVERVIEW
Status:
Completed; FDA label changed
ClinicalTrials.gov identifier:
NCT00734539
NICHD Data and Specimen Hub (DASH):
- Fluconazole - Supplemental Data to Provide Additional Evidence of Safety and Efficacy for the Proposed Dosing Regimens of Fluconazole in Infants and Young Children
- Fluconazole - Prophylaxis for Prevention of Candidiasis in Infants
- Fluconazole - Secondary Analysis of Data from Prophylaxis Study
- Fluconazole - Safety/PK in Children Supported with Extracorporeal Membrane Oxygenation
- Fluconazole - PK of Loading Dose in Infants and Toddlers
Principal Investigators:
P. Brian Smith, MD, MPH, MHS and Daniel K. Benjamin, MD, PhD, MPH
Duke Health, Durham, NC
NEWS
- PTN Research Informs Fluconazole Label ChangeData from multiple Pediatric Trials Network (PTN) studies contributed to a recent U.S. Food and Drug Administration (FDA) label change for fluconazole. The data that informed the label update, which is extensive, came from the following studies: Fluconazole Prophylaxis for the Prevention of Candidiasis in Infants < 750 Grams Birth Weight Pharmacokinetics of a Fluconazole Loading Dose ...
- Red Book updated with fluconazole dosing information from PTN studyThe American Academy of Pediatrics (AAP) has updated the 2018 edition of the Red Book to include fluconazole dosing information determined by a Pediatric Trials Network (PTN) study. The Red Book is the leading resource on pediatric infectious disease, providing the most up-to-date information on a wide variety of diseases that doctors see in children. The ...
- Population Pharmacokinetics of Fluconazole in Premature Infants with Birth Weights Less than 750 GramsAntimicrobial Agents and Chemotherapy • August 2016. Momper JD, Capparelli EV, Wade KC, Kantak A, Dhanireddy R, Cummings JJ, Nedrelow JH, Hudak ML, Mundakel GT, Natarajan G, Gao J, Laughon M, Smith PB, Benjamin DK Jr. Fluconazole is an effective agent for prophylaxis of invasive candidiasis in premature infants. The objective of this study was to characterize ...
- Fluconazole Prophylaxis for the Prevention of Candidiasis in Premature Infants: A Meta-analysis Using Patient-level DataClinical Infectious Diseases • August 2016. Ericson JE, Kaufman DA, Kicklighter SD, Bhatia J, Testoni D, Gao J, Smith PB, Prather KO, Benjamin DK Jr; Fluconazole Prophylaxis Study Team on behalf of the Best Pharmaceuticals for Children Act–Pediatric Trials Network Steering Committee. Invasive candidiasis (IC) is an important cause of sepsis in premature infants and is associated ...
- Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenationAntimicrobial Agents and Chemotherapy • June 2015. Watt KM, Gonzalez D, Benjamin DK Jr, Brouwer KL, Wade KC, Capparelli E, Barrett J, Cohen-Wolkowiez M. Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptimal ...
- Editorial commentary: Fluconazole therapeutic drug monitoring in children with cancer: not todayClinical Infectious Disease • December 2014. Cohen-Wolkowiez M, Benjamin DK Jr. This editorial focuses on insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children. Access article on PubMed.
- Effect of fluconazole prophylaxis on candidiasis and mortality in premature infants: a randomized clinical trialJAMA • June 2014. Benjamin DK Jr, Hudak ML, Duara S, Randolph DA, Bidegain M, Mundakel GT, Natarajan G, Burchfield DJ, White RD, Shattuck KE, Neu N, Bendel CM, Kim MR, Finer NN, Stewart DL, Arrieta AC, Wade KC, Kaufman DA, Manzoni P, Prather KO, Testoni D, Berezny KY, Smith PB; Fluconazole Prophylaxis Study Team. Invasive candidiasis in ...
- The fluconazole prophylaxis study locks its databaseThe PTN team behind the Safety of Fluconazole Prophylaxis in Infants study successfully locked the Benjamin study database last week. To evaluate the safety of fluconazole, the team is gathering randomized trial datasets from several thought leaders to perform a data meta-analysis—the Benjamin study comprises the first of these datasets. The PTN will examine safety ...