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Adverse Event Detection and Labeling in Pediatric Drug Development: Antiretroviral Drugs

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Abstract

Background: Pediatric safety studies are conducted for drugs undergoing development for use in pediatric patients. The objective of this study was to describe safety studies and compare adverse events of antiretroviral drugs between pediatric patients and adult subjects. Methods: Pediatric and adult adverse event data were obtained from US Food and Drug Administration (FDA)–approved drug labels for 9 antiretroviral drugs with pediatric indications approved by the FDA prior to 2013. For adverse events (AEs) reported in both pediatric patients and adult subjects, the risk difference (RD) and associated confidence interval (CI) were calculated. Results: Of 35 drug-AE combinations, 10 AEs were reported at statistically significantly (P <.05) higher incidence rates in the pediatric population than in the adult population, and 3 AEs were reported at statistically significantly higher rates in the adult population than in the pediatric population. The largest differences where the risk of an AE was greater in pediatric patients than in adult subjects were for rash with efavirenz (RD = 36.24% [95% CI, 21.1 to 50.53]), diarrhea with efavirenz (RD = 24.53% [95% CI, 9.06 to 39.57]), and rash with nevirapine (RD = 16.14% [95% CI, 9.7 to 24.27]). The largest differences where the risk of an adverse event was lower in pediatric patients than in adult subjects were for headache with abacavir (RD = −12% [95% CI, −16.81 to −6.89]), diarrhea with tipranavir (RD = −11.32% [95% CI, −15.02 to −5.6]), and diarrhea with lamivudine (RD = −9.88% [95% CI, −15.91 to −3.98]). Conclusions: The adult adverse event experience provides preliminary data for pediatric drug safety, yet the specific types of adverse effects and frequencies may not be predicted in children based exclusively on adults. As adult safety data do not fully inform the pediatric safety profile, pediatric safety studies should continue to be conducted separately for drugs undergoing testing in pediatric patients.

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Authors and Affiliations

  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA

    Jeremiah D. Momper PharmD, PhD & Edmund V. Capparelli PharmD

  2. Division of Bioequivalence, Office of Generic Drugs, US Food and Drug Administration, Silver Spring, MD, USA

    Yang Chang PhD, PharmD

  3. Office of Biostatistics, Office of Translational Sciences, US Food and Drug Administration, Silver Spring, MD, USA

    Matthew Jackson PhD & Paul Schuette PhD

  4. Office of Clinical Pharmacology, Office of Translational Sciences, CDER, US Food and Drug Administration, White Oak Building 51, Room 3184, 10903 New Hampshire Ave, Silver Spring, MD, 20903, USA

    Shirley Seo PhD, Islam Younis PhD, Darrell R. Abernethy MD, PhD & Gilbert J. Burckart PharmD

  5. Division of Pediatric and Maternal Health, Office of New Drugs, US Food and Drug Administration, Silver Spring, MD, USA

    Lynne Yao MD

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  1. Jeremiah D. Momper PharmD, PhD
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  2. Yang Chang PhD, PharmD
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  3. Matthew Jackson PhD
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  4. Paul Schuette PhD
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  5. Shirley Seo PhD
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  6. Islam Younis PhD
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  7. Darrell R. Abernethy MD, PhD
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  8. Lynne Yao MD
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  9. Edmund V. Capparelli PharmD
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  10. Gilbert J. Burckart PharmD
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Correspondence to Gilbert J. Burckart PharmD.

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The opinions expressed in this work are those of the authors and should not be interpreted as the position of the US Food and Drug Administration.

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Momper, J.D., Chang, Y., Jackson, M. et al. Adverse Event Detection and Labeling in Pediatric Drug Development: Antiretroviral Drugs. Ther Innov Regul Sci 49, 302–309 (2015). https://doi.org/10.1177/2168479014565471

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  • DOI: https://doi.org/10.1177/2168479014565471

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