Safety of Fluconazole Prophylaxis and Treatment in Infants

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:

  1. Fluconazole Prophylaxis for the Prevention of Candidiasis in Infants < 750 Grams Birth Weight
  2. Pharmacokinetics of a Fluconazole Loading Dose in Infants and Toddlers
  3. Safety and Pharmacokinetics of Fluconazole in Children Supported by Extracorporeal Membrane Oxygenation (ECMO)
  4. 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

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):

Principal Investigators:
P. Brian Smith, MD, MPH, MHS and Daniel K. Benjamin, MD, PhD, MPH
Duke Health, Durham, NC

Results-at-a-Glance

Label Change

The update to the label is very extensive and involves data from multiple studies and analyses supported by PTN.

The old label contained almost no information related to how to use this drug in infants, even though it is commonly used to treat Candida (yeast) infections, which are often fatal in infants and cause long-lasting health problems for those that survive.

The new label contains information generated and submitted by PTN on pharmacokinetics and dosing suggestions (including the use of a “loading” or initial higher dose), as well as safety and efficacy of fluconazole for both treatment and prophylaxis (prevention) of Candida infections in full-term and premature infants.

Importantly, information on dosing for pediatric patients on ECMO is also newly included.

NEWS