Prescription Medication Use Among Children and Adolescents in the United States

Qato, Dima M.; Alexander, G. Caleb; Guadamuz, Jenny S.; Lindau, Stacy Tessler

doi:10.1542/peds.2018-1042

Cited by 45 publications

(43 citation statements)

References 29 publications

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“…C ytochrome P450 2C19 (CYP2C19) metabolizes multiple selective serotonin reuptake inhibitors (SSRIs) (Wang et al 2001;Chang et al 2014;Steere et al 2015), including sertraline, citalopram, and its s-enantiomer, escitalopram. Both escitalopram and sertraline are FDA approved for pediatric use, effectively treat anxiety (March et al 1998;Rynn et al 2001;Walkup et al 2008) and depressive disorders ) in youth, and are commonly prescribed to pediatric patients (Qato et al 2018). To date, more than two dozen variants in the CYP2C19 gene have been identified, and these are associated with varying metabolic activity and include loss-of-function alleles (e.g., null alleles *2-*9) as well as alleles with increased activity (e.g., *17).…”

Section: Introductionmentioning

confidence: 99%

CYP2C19-Guided Escitalopram and Sertraline Dosing in Pediatric Patients: A Pharmacokinetic Modeling Study

Poweleit

Ramsey

2019

Journal of Child and Adolescent Psychopharmacology

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Objective: Cytochrome P4502C19 (CYP2C19) is a highly polymorphic gene that encodes an enzyme that metabolizes escitalopram and sertraline, two selective serotonin reuptake inhibitors (SSRIs) that are FDA approved for pediatric use and commonly used to treat anxiety and depressive disorders in youth. Using pharmacokinetic (PK) models in adolescents, we sought to (1) model SSRI dosing across CYP2C19 phenotypes to compare SSRI exposure (area under curve, AUC) and maximum concentration (C max ), (2) evaluate the impact of b.i.d. dosing (in rapid metabolizers [RM] and ultrarapid metabolizers [UM]) on SSRI exposure and C max , and (3) determine pharmacogenomically-informed dosing strategies to provide similar exposure across CYP2C19 phenotypes in adolescents. Methods: Using PK parameters in CYP2C19 phenotype groups and previously reported pediatric PK data for escitalopram and sertraline, we modeled exposure (AUC 0-24 ) and C max and determined CYP2C19-guided dosing strategies. Results: Compared with normal CYP2C19 metabolizers treated with either escitalopram or sertraline, C max and AUC 0-24 were higher in slower metabolizers and lower in patients with increased CYP2C19 activity, although the magnitude of these differences was more pronounced for escitalopram than for sertraline. For escitalopram, poor metabolizers (PMs) require 10 mg/day and UMs require 30 mg/day to achieve an exposure that is equivalent to 20 mg/day in a normal metabolizer (NM). For sertraline, to achieve AUC 0-24 and C max similar to NMs receiving 150 mg/day, PMs require 100 mg/day, whereas a dose of 200 mg/day was required in rapid and UMs. For UMs, b.i.d. escitalopram dosing was necessary to achieve comparable trough levels and exposure to NMs. Conclusions: This simulation study raises the possibility that achieving similar escitalopram and sertraline plasma concentrations could require dose adjustments in CYP2C19 poor metabolizers and UMs, although the magnitude of these differences were more pronounced for escitalopram than for sertraline. However, prospective trials of pharmacogenomically guided dosing in the pediatric population are needed to extend the findings of these modeling studies.

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Section: Introductionmentioning

confidence: 99%

CYP2C19-Guided Escitalopram and Sertraline Dosing in Pediatric Patients: A Pharmacokinetic Modeling Study

Poweleit

Ramsey

2019

Journal of Child and Adolescent Psychopharmacology

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“…Data on prescription medication use were available for 38,277 children and adolescents from 1999 to 2014, and Hales et al 13 found that the overall use of any prescription medication in the past 30 days was 21.9%. During 2013-2014, Qato et al 14 found that 19.8% of children and adolescents were prescribed at least 1 medication, and 7.5% used multiple medications. Rieder 15 reported on a population of 1 million Canadian children and noted that about 20% of all prescriptions were written for 70% of patients, which suggested that patients with complex or chronic diseases frequently receive polytherapy.…”

Section: Introductionmentioning

confidence: 99%

Key PotentiallyInappropriateDrugs in Pediatrics: The KIDs List

Meyers¹,

Thackray²,

Matson³

et al. 2020

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVES The safe use of medications in pediatric patients requires practitioners to consider the unique pharmacokinetics and pharmacodynamics of drugs prescribed in this age group. In an effort to create a standard of care for the safe use of medications in this population, a list of drugs that are potentially inappropriate for use in pediatric patients has been developed and titled the “KIDs List.” METHODS A panel of 7 pediatric pharmacists from the Pediatric Pharmacy Association were recruited to evaluate primary, secondary, and tertiary literature; FDA Pediatric Safety Communications; the Lexicomp electronic database; and product information for drugs that should be considered potentially inappropriate for use in pediatric patients. Information was rated using predefined criteria. A PubMed search was conducted using the following terms: adverse drug events OR adverse drug reactions. The search was limited to humans; age <18 years; case reports, observational studies, or clinical trials; and English language. No date range was used. Results were used to create an evidence-based list of candidate drugs that was then peer-reviewed and subjected to a 30-day public comment period prior to being finalized. RESULTS A PubMed search yielded 4049 unique titles, of which 210 were deemed relevant for full review. Practitioner recommendations highlighted an additional 77 drugs. FDA Pediatric Safety Communications and the Lexicomp database yielded 22 and 619 drugs, respectively. After critical analysis, peer review, and public review the final KIDs List contains 67 drugs and/or drug classes and 10 excipients. CONCLUSIONS This extensive effort led to compilation of the first list of drugs that are potentially inappropriate for prescribing in all or in a select subgroup of pediatric patients. If avoidance is not clinically possible, the drug should be used with caution and accompanied by appropriate monitoring.

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“…1 Most prescriptions are for short-term antibiotics; but many are for longer-term use medications that are used to treat chronic health conditions. [1][2][3] The use of chronic medications (CMs) is not without risk and presents a management challenge in both outpatient and community settings due to the time and effort required to review, reconcile, and monitor CM use. [4][5][6][7][8][9][10][11] The National Academy of Sciences has designated the outpatient environment as a high-priority area for medication safety in children.…”

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confidence: 99%

Chronic Medication Use in Children Insured by Medicaid: A Multistate Retrospective Cohort Study

et al. 2019

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BACKGROUND AND OBJECTIVES: Little is known about the use of chronic medications (CMs) in children. We assessed the prevalence of CM use in children and the association of clinical characteristics and health care resource use with the number of CMs used. METHODS: This is a retrospective study of children ages 1 to 18 years using Medicaid from 10 states in 2014 grouped by the annual number of CMs (0, 1, 2-4, 5-9, and $10 medications), which are defined as a dispensed $30-day prescription with $2 dispensed refills. Trends in clinical characteristics and health care use by number of CMs were evaluated with the Cochran-Armitage trend test. RESULTS: Of 4 594 061 subjects, 18.8% used CMs. CM use was 44.4% in children with a complex chronic condition. Across all children, the most common CM therapeutic class was neurologic (28.9%). Among CM users, 48.8% used multiple CMs (40.3% used 2-4, 7.0% used 5-9, and 0.5% used $10). The diversity of medications increased with increasing number of CMs: for 1 CM, amphetamine stimulants were most common (29.0%), and for $10 CMs, antiepileptics were most common (7.1%). Of $2.3 billion total pharmacy spending, 59.3% was attributable to children dispensed multiple CMs. Increased CM use (0 to $10 medications) was associated with increased emergency department use (32.1% to 56.2%) and hospitalization (2.3% to 36.7%). CONCLUSIONS: Nearly 1 in 5 children with Medicaid used CMs. Use of multiple CMs was common and correlated with increased health care use. Understanding CM use in children should be fundamentally important to health care systems when strategizing how to provide safe, evidence-based, and cost-effective pharmaceutical care to children. WHAT'S KNOWN ON THIS SUBJECT: Children insured by Medicaid frequently use medications, but little is known specifically about chronic medication (CM) use. Without understanding which children use CMs, it is challenging to plan investigations to determine the appropriateness of current prescription practices. WHAT THIS STUDY ADDS: One in 5 children insured by Medicaid use a CM annually; nearly 1 in 10 used multiple CMs. Central nervous system agents accounted for nearly 30% of all CMs. CMs were positively correlated with health care resource use and spending.

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Prescription Medication Use Among Children and Adolescents in the United States

Cited by 45 publications

References 29 publications

CYP2C19-Guided Escitalopram and Sertraline Dosing in Pediatric Patients: A Pharmacokinetic Modeling Study

CYP2C19-Guided Escitalopram and Sertraline Dosing in Pediatric Patients: A Pharmacokinetic Modeling Study

Key PotentiallyInappropriateDrugs in Pediatrics: The KIDs List

Chronic Medication Use in Children Insured by Medicaid: A Multistate Retrospective Cohort Study

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