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Original Investigation |

Drug Labeling and Exposure in Neonates

Matthew M. Laughon, MD, MPH1; Debbie Avant, RPh2; Nidhi Tripathi, MD3; Christoph P. Hornik, MD3; Michael Cohen-Wolkowiez, MD, PhD3; Reese H. Clark, MD4; P. Brian Smith, MD, MPH, MHS3; William Rodriguez, MD, PhD2
[+] Author Affiliations
1Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill
2Food and Drug Administration, Rockville, Maryland
3Duke Clinical Research Institute and Duke University Medical Center, Durham, North Carolina
4Pediatrix Center for Research and Education, Sunrise, Florida
JAMA Pediatr. 2014;168(2):130-136. doi:10.1001/jamapediatrics.2013.4208.
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Importance  Federal legislation has led to a notable increase in pediatric studies submitted to the Food and Drug Administration (FDA), resulting in new pediatric information in product labeling. However, approximately 50% of drug labels still have insufficient information on safety, efficacy, or dosing in children. Neonatal information in labeling is even scarcer because neonates comprise a vulnerable subpopulation for which end-point development is lagging and studies are more challenging.

Objective  To quantify progress made in neonatal studies and neonatal information in product labeling as a result of recent legislation.

Design, Setting, and Participants  We identified a cohort of drug studies between 1997 and 2010 that included neonates as a result of pediatric legislation using information available on the FDA website. We determined what studies were published in the medical literature, the legislation responsible for the studies, and the resulting neonatal labeling changes. We then examined the use of these drugs in a cohort of neonates admitted to 290 neonatal intensive care units (NICUs) (the Pediatrix Data Warehouse) in the United States from 2005 to 2010.

Exposure  Infants exposed to a drug studied in neonates as identified by the FDA website.

Main Outcomes and Measures  Number of drug studies with neonates and rate of exposure per 1000 admissions among infants admitted to an NICU.

Results  In a review of the FDA databases, we identified 28 drugs studied in neonates and 24 related labeling changes. Forty-one studies encompassed the 28 drugs, and 31 (76%) of these were published. Eleven (46%) of the 24 neonatal labeling changes established safety and effectiveness. In a review of a cohort of 446 335 hospitalized infants, we identified 399 drugs used and 1 525 739 drug exposures in the first 28 postnatal days. Thirteen (46%) of the 28 drugs studied in neonates were not used in NICUs; 8 (29%) were used in fewer than 60 neonates. Of the drugs studied, ranitidine was used most often (15 627 neonates, 35 exposures per 1000 admissions).

Conclusions and Relevance  Few drug labeling changes made under pediatric legislation include neonates. Most drugs studied are either not used or rarely used in US NICUs. Strategies to increase the study of safe and effective drugs for neonates are needed.

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Neonatal Labeling Changes Under Legislation From 1997 to 2010 and Exposure of Neonates to Drugs With a Neonatal Indication

aThere are 24 neonatal labeling changes involving 23 drugs. Linezolid has 2 labeling changes.

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