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. 2014 Feb;168(2):130-6.
doi: 10.1001/jamapediatrics.2013.4208.

Drug labeling and exposure in neonates

Matthew M Laughon  1 , Debbie Avant  2 , Nidhi Tripathi  3 , Christoph P Hornik  3 , Michael Cohen-Wolkowiez  3 , Reese H Clark  4 , P Brian Smith  3 , William Rodriguez  2
Affiliations

Drug labeling and exposure in neonates

Matthew M Laughon et al. JAMA Pediatr. 2014 Feb.

Abstract

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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Conflict of interest statement

Christoph P. Hornik, Nidhi Tripathi, Reese H. Clark, William Rodriguez, and Debbie Avant have no relevant conflicts to disclose.

Figures

Figure
Figure
Neonatal labeling changes under legislation from 1997–2010 and exposure of neonates to drugs with a neonatal indication. *There are 24 neonatal labeling changes involving 23 drugs. Linezolid has 2 labeling changes.
See this image and copyright information in PMC

Comment in

References

    1. Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349(12):1157–1167. - PubMed
    1. Andersen DH, Blanc WA, Crozier DN, Silverman WA. A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics. 1956;18(4):614–625. - PubMed
    1. Stewart DJ. The effects of tetracyclines upon the dentition. Br J Dermatol. 1964;76:374–378. - PubMed
    1. Burns LE, Hodgman JE, Cass AB. Fatal circulatory collapse in premature infants receiving chloramphenicol. N Engl J Med. 1959;261:1318–1321. - PubMed
    1. Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics. 1998;101(5):E7. - PubMed

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