Literature DB >> 24322269

Drug labeling and exposure in neonates.

Matthew M Laughon1, Debbie Avant2, Nidhi Tripathi3, Christoph P Hornik3, Michael Cohen-Wolkowiez3, Reese H Clark4, P Brian Smith3, William Rodriguez2.   

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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Year:  2014        PMID: 24322269      PMCID: PMC3927948          DOI: 10.1001/jamapediatrics.2013.4208

Source DB:  PubMed          Journal:  JAMA Pediatr        ISSN: 2168-6203            Impact factor:   16.193


  42 in total

1.  [The incidence of prescriptions without marketing product license in a neonatal intensive care unit].

Authors:  S Avenel; A Bomkratz; G Dassieu; J C Janaud; C Danan
Journal:  Arch Pediatr       Date:  2000-02       Impact factor: 1.180

2.  The safety and efficacy of sevoflurane anesthesia in infants and children with congenital heart disease.

Authors:  I A Russell; W C Miller Hance; G Gregory; M C Balea; L Cassorla; A DeSilva; R F Hickey; L M Reynolds; K Rouine-Rapp; F L Hanley; V M Reddy; M K Cahalan
Journal:  Anesth Analg       Date:  2001-05       Impact factor: 5.108

Review 3.  NIH consensus development conference: Inhaled nitric oxide therapy for premature infants.

Authors:  F Sessions Cole; Claudia Alleyne; John D E Barks; Robert J Boyle; John L Carroll; Deborah Dokken; William H Edwards; Michael Georgieff; Katherine Gregory; Michael V Johnston; Michael Kramer; Christine Mitchell; Josef Neu; DeWayne M Pursley; Walter Robinson; David H Rowitch
Journal:  NIH Consens State Sci Statements       Date:  2010-10-29

4.  Pharmacokinetics and pharmacodynamics of sotalol in a pediatric population with supraventricular and ventricular tachyarrhythmia.

Authors:  J P Saul; B Ross; M S Schaffer; L Beerman; A P Melikian; J Shi; J Williams; J T Barbey; J Jin; P H Hinderling
Journal:  Clin Pharmacol Ther       Date:  2001-03       Impact factor: 6.875

5.  Pharmacokinetics and pharmacodynamics of famotidine in infants.

Authors:  L P James; T Marotti; C D Stowe; H C Farrar; B J Taylor; G L Kearns
Journal:  J Clin Pharmacol       Date:  1998-12       Impact factor: 3.126

6.  A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles.

Authors:  P J Davis; J Galinkin; F X McGowan; A M Lynn; M Yaster; M F Rabb; E J Krane; C D Kurth; R H Blum; L Maxwell; R Orr; P Szmuk; D Hechtman; S Edwards; L G Henson
Journal:  Anesth Analg       Date:  2001-12       Impact factor: 5.108

7.  A survey of the use of off-label and unlicensed drugs in a Dutch children's hospital.

Authors:  G W 't Jong; A G Vulto; M de Hoog; K J Schimmel; D Tibboel; J N van den Anker
Journal:  Pediatrics       Date:  2001-11       Impact factor: 7.124

8.  Pharmacokinetics of zidovudine and lamivudine in neonates following coadministration of oral doses every 12 hours.

Authors:  D Moodley; K Pillay; K Naidoo; J Moodley; M A Johnson; K H Moore; P N Mudd; G E Pakes
Journal:  J Clin Pharmacol       Date:  2001-07       Impact factor: 3.126

9.  Single-dose pharmacokinetics of sotalol in a pediatric population with supraventricular and/or ventricular tachyarrhythmia.

Authors:  J P Saul; M S Schaffer; P P Karpawich; C C Erickson; M R Epstein; A P Melikian; J Shi; A H Karara; B Cai; P H Hinderling
Journal:  J Clin Pharmacol       Date:  2001-01       Impact factor: 3.126

10.  Pharmacokinetics of stavudine and didanosine coadministered with nelfinavir in human immunodeficiency virus-exposed neonates.

Authors:  C Rongkavilit; P Thaithumyanon; T Chuenyam; B D Damle; S Limpongsanurak; C Boonrod; A Srigritsanapol; E A Hassink; R M Hoetelmans; D A Cooper; J M Lange; K Ruxrungtham; P Phanuphak
Journal:  Antimicrob Agents Chemother       Date:  2001-12       Impact factor: 5.191

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  39 in total

1.  Methodological and Ethical Issues in Pediatric Medication Safety Research.

Authors:  Delesha Carpenter; Daniel Gonzalez; George Retsch-Bogart; Betsy Sleath; Benjamin Wilfond
Journal:  Pediatrics       Date:  2017-08-04       Impact factor: 7.124

2.  Off-label and unlicensed drug treatments in Neonatal Intensive Care Units: an Italian multicentre study.

Authors:  Laura Cuzzolin; Rocco Agostino
Journal:  Eur J Clin Pharmacol       Date:  2016-01       Impact factor: 2.953

Review 3.  Collaboration in Regulatory Science to Facilitate Therapeutic Development for Neonates.

Authors:  Susan K McCune; Yeruk Ager Mulugeta; Gerri R Baer
Journal:  Curr Pharm Des       Date:  2017       Impact factor: 3.116

4.  Newborns still lack drug data to guide therapy.

Authors:  Robert M Ward; Catherine M Sherwin
Journal:  Br J Clin Pharmacol       Date:  2016-10-03       Impact factor: 4.335

5.  Standardizing Safety Assessment and Reporting for Neonatal Clinical Trials.

Authors:  Jonathan M Davis; Gerri R Baer; Susan McCune; Agnes Klein; Junko Sato; Laura Fabbri; Alexandra Mangili; Mary A Short; Susan Tansey; Barry Mangum; Isamu Hokuto; Hidefumi Nakamura; Thomas Salaets; Karel Allegaert; Lynne Yao; Michael Blum; Joseph Toerner; Mark Turner; Ron Portman
Journal:  J Pediatr       Date:  2019-11-08       Impact factor: 4.406

6.  Neonatal Safety Information Reported to the FDA During Drug Development Studies.

Authors:  Debbie Avant; Gerri Baer; Jason Moore; Panli Zheng; Alfred Sorbello; Ron Ariagno; Lynne Yao; Gilbert J Burckart; Jian Wang
Journal:  Ther Innov Regul Sci       Date:  2017-06-28       Impact factor: 1.778

7.  The EU paediatric regulation: still a large discrepancy between therapeutic needs and approved paediatric investigation plans.

Authors:  Stefan Wimmer; Wolfgang Rascher; Suzanne McCarthy; Antje Neubert
Journal:  Paediatr Drugs       Date:  2014-10       Impact factor: 3.022

8.  The Need for Pediatric Drug Development.

Authors:  Robert M Ward; Daniel K Benjamin; Jonathan M Davis; Richard L Gorman; Ralph Kauffman; Gregory L Kearns; Mary Dianne Murphy; Catherine M T Sherwin
Journal:  J Pediatr       Date:  2017-09-21       Impact factor: 4.406

Review 9.  Drug-induced acute kidney injury in neonates.

Authors:  Mina H Hanna; David J Askenazi; David T Selewski
Journal:  Curr Opin Pediatr       Date:  2016-04       Impact factor: 2.856

10.  Medication Repurposing in Pediatric Patients: Teaching Old Drugs New Tricks.

Authors:  Martha M Rumore
Journal:  J Pediatr Pharmacol Ther       Date:  2016 Jan-Feb
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