Original Investigation |

Adolescent Dosing and Labeling Since the Food and Drug Administration Amendments Act of 2007

Jeremiah D. Momper, PharmD, PhD1; Yeruk Mulugeta, PharmD1; Dionna J. Green, MD1; Alyson Karesh, MD2; Kevin M. Krudys, PhD1; Hari C. Sachs, MD2; Lynn P. Yao, MD2; Gilbert J. Burckart, PharmD1
[+] Author Affiliations
1Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
2Pediatric and Maternal Health Staff, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland
JAMA Pediatr. 2013;167(10):926-932. doi:10.1001/jamapediatrics.2013.465.
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Importance  During pediatric drug development, dedicated pharmacokinetic studies are generally performed in all relevant age groups to support dose selection for subsequent efficacy trials. To our knowledge, no previous assessments regarding the need for an intensive pharmacokinetic study in adolescents have been performed.

Objectives  To compare US Food and Drug Administration (FDA)–approved adult and adolescent drug dosing and to assess the utility of allometric scaling for the prediction of drug clearance in the adolescent population.

Design  Adult and adolescent dosing and drug clearance data were obtained from FDA-approved drug labels and publicly available databases containing reviews of pediatric trials submitted to the FDA. Dosing information was compared for products with concordant indications for adolescent and adult patients. Adolescent drug clearance was predicted from adult pharmacokinetic data by using allometric scaling and compared with observed values.

Main Outcomes and Measures  Adolescent and adult dosing information and drug clearance.

Results  There were 126 unique products with pediatric studies submitted to the FDA since the FDA Amendments Act of 2007, of which 92 had at least 1 adolescent indication concordant with an adult indication. Of these 92 products, 87 (94.5%) have equivalent dosing for adults and adolescent patients. For 18 of these 92 products, a minimum weight or body surface area threshold is recommended for adolescents to receive adult dosing. Allometric scaling predicted adolescent drug clearance with an overall mean absolute percentage error of 17.0%.

Conclusions and Relevance  Approved adult and adolescent drug dosing is equivalent for 94.5% of products with an adolescent indication studied since the FDA Amendments Act of 2007. Allometric scaling may be a useful tool to avoid unnecessary dedicated pharmacokinetic studies in the adolescent population during pediatric drug development, although each development program in adolescents requires a full discussion of drug dosing with the FDA.

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Figure 1.
Distribution of Products Reviewed

Dosing and drug clearance were assessed for the 126 products reviewed. IV indicates intravenous; PK, pharmacokinetic.

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Figure 2.
Linear Regression of Observed vs Predicted Clearance in Adolescents

A, Observed vs predicted clearance (CL) in adolescents for drugs administered intravenously. B, Observed vs predicted apparent oral clearance (CL/F, where F represents oral bioavailability) in adolescents for drugs administered orally.

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