sign in sign up
<<
Home , Analgesic

Trends in Dispensed Prescriptions to Children in South Carolina: 2010–2017 William T. Basco, Jr, MD, MS,a Jenna L. McCauley, PhD,b Jingwen Zhang, MS,c Patrick D. Mauldin, PhD,c Kit N. Simpson, DrPH,d Khosrow Heidari, MA, MS,e Justin E. Marsden, BS,c Sarah J. Ball, PharmDc

BACKGROUND AND OBJECTIVES: Despite published declines in opioid prescribing and dispensing to abstract children in the past decade, in few studies have researchers evaluated all children in 1 state or examined changes in mean daily opioid dispensed. In this study, we evaluated changes in the rate of dispensed opioid and the mean daily opioid dispensed to persons 0 to 18 years old in 1 state over an 8-year period. METHODS: We identified opioid analgesics dispensed to children 0 to 18 years old between 2010 and 2017 using South Carolina prescription program data. We used generalized linear regression analyses to examine changes over time in the following: (1) rate of dispensed opioid prescriptions and (2) mean daily milligram equivalents (MMEs) per prescription. RESULTS: From the first quarter of 2010 to the end of the fourth quarter of 2017, the quarterly rate of dispensed decreased from 18.68 prescriptions per 1000 state residents to 12.03 per 1000 residents (P , .0001). The largest declines were among the oldest individuals, such as the 41.2% decline among 18-year-olds. From 2010 through 2017, the mean daily MME dispensed declined by 7.6%, from 40.7 MMEs per day in 2010 to 37.6 MMEs per day in 2017 (P , .0001), but the decrease was limited to children 0 to 9 years old. CONCLUSIONS: The rate of opioid analgesic prescriptions dispensed to children 0 to 18 years old in South Carolina declined by 35.6% over the years 2010–2017; however, the MME dispensed per day declined minimally, suggesting that more can be done to improve opioid prescribing and dispensing.

’ Departments of aPediatrics, bPsychiatry and Behavioral Sciences, and cMedicine, College of Medicine, and WHAT S KNOWN ON THIS SUBJECT: Studies have revealed dDepartment of Healthcare Leadership and Management, College of Health Professions, Medical University of decreases in opioid dispensing, but no researchers have South Carolina, Charleston, South Carolina; and eBlueCross BlueShield of South Carolina, Columbia, South looked at opioid analgesic dispensing for all children in 1 Carolina state using monitoring program data, Drs Ball, Basco, and Mauldin conceptualized and designed the study, interpreted analyses, and and few have evaluated changes in mean daily opioid wrote, reviewed, and revised the manuscript; Drs McCauley and Simpson provided input on the dispensed. design of the study, interpreted analyses, and reviewed and revised the manuscript; Ms Zhang and WHAT THIS STUDY ADDS: In these data, dispensed opioid fi Mr Marsden conducted data veri cation steps and data analyses, assisted with interpretation of analgesic prescriptions declined by 35.6% between 2010 fi analyses, produced the tables and gures, and reviewed and revised the manuscript; Mr Heidari and 2017, but the mean daily opioid dispensed, measured provided content expertise on the databases used and reviewed and assisted with revision of the in morphine milligram equivalents, declined by only 7.6% manuscript; and all authors approved the final manuscript as submitted. for all children and only among those 0 to 9 years old. DOI: https://doi.org/10.1542/peds.2020-0649 Accepted for publication Nov 24, 2020 To cite: Basco WT, McCauley JL, Zhang J, et al. Trends in Dispensed Opioid Analgesic Prescriptions to Children in Address correspondence to William T. Basco Jr, MD, MS, Division of General Pediatrics, Medical South Carolina: 2010–2017. Pediatrics. 2021;147(3): University of South Carolina, 135 Rutledge Ave, MSC 561, Charleston, SC 29425. E-mail: bascob@ e20200649 musc.edu

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 147, number 3, March 2021:e20200649 ARTICLE Children are a less explored group population to 10 opioid analgesic allchildreninastateregardlessof compared with adults in regard to the prescriptions per 1000 population location of care, age, or payer. The effects of the , but between 1999 and 2014.14 All these second gap we sought to address was children experience harm as a result studies excluded children 0 to 2 years whether changes in the rate of of the opioid epidemic as well.1–3 old. dispensed opioid prescriptions was Studies have revealed increases in accompanied by a change in daily MME. Dispensed prescription rates provide births affected by neonatal opioid only 1 measure of opioid prescribing withdrawal syndrome, the number of and dispensing. Another measure of METHODS young children accidentally ingesting interest is the daily amount of opioid opioids prescribed to other Subjects dispensed, measured in morphine household members, and pediatric milligram equivalents (MMEs) to The subjects were aged 0 to 18 years hospital admissions due to opioid standardize the potency of the at the time they appeared in the poisonings and a striking increase in different opioids. In Tennessee South Carolina PDMP data between PICU admissions due to opioid Medicaid claims data for children 2 to 2010 and 2017 as a result of exposures, both intentional and – 17 years old, daily MME dispensed receiving one of the opioids on the accidental.4 6 Childhood deaths due correlated with the risk of adverse study list, described later. to prescribed and illicit opioid use events such as ED visit, hospital continue to increase.3,7,8 Proper admission, or death.14 Among Data opioid stewardship involves privately insured subjects 12 to 21 The South Carolina Reporting & navigating the ethical balance years old, the daily MME correlated Identification Tracking System between treating patients and not with the risk of overdose.13 Less is (SCRIPTS), South Carolina’s PDMP inducing harm.9 known about changes in daily MME registry, went into effect in 2008 Focusing on the rate opioids are on a population level over time. under the maintenance of the Bureau dispensed to children is important Although a single-institution study of of Drug Control at the South Carolina because even indicated opioid postoperative opioid prescribing to Department of Health and prescribing and use among children children 0 to 18 years old revealed Environmental Control (DHEC). and adolescents confers risks, concurrent declines in opioid SCRIPTS collects data through daily ’ – including adverse drug events and prescription numbers, days supply, downloads on Schedule II Schedule the possibility of potentially and daily dose between 2013 and IV controlled substances dispensed in predisposing opioid-exposed children 2017, there are concerns that state- South Carolina or by mail-order fi to opioid misuse in young speci c regulatory limitations on pharmacies for South Carolina ’ adulthood.10–13 Although recent days supply of opioids that can be residents. In 2016, researchers at our reports reveal downward trends in prescribed may lead prescribers to institution commenced a partnership prescribe higher MME per day, as has with the South Carolina DHEC to opioid prescriptions for children 16 overall, the studies have been been seen in adult data. evaluate South Carolina PDMP data. On receipt of eight 12-month de- completed in single settings, such as We conducted this study to address identified SCRIPTS data sets, we emergency departments (EDs), have two gaps in the pediatric opioid completed data quality activities. evaluated one payer source (eg, pharmacoepidemiology literature Using initial data quality checks, we Medicaid), or have excluded younger using South Carolina prescription identified minor gaps in SCRIPTS data children, such as those 0 to 2 years drug monitoring program (PDMP) 11,14,15 for correction. old. National estimates of data from 2010 to 2017. One prescribing after an ED visit advantage of PDMP data is that all Demographic data available in the by children aged 3 to 17 revealed controlled substance prescriptions PDMP included age at the time of a decline from 3.7% to 2.9% of visits dispensed in a state are captured, dispensing. We used age as associated with a codeine regardless of patient funding source, a continuous variable in 1-year prescription from 2001 to 2010, and thereby giving a more complete increments (eg, 0–1 year old = infant) National Hospital Ambulatory population-based estimate of up to age 18 (age 18 years, plus 364 Medical Care Survey data from 2005 ambulatory child opioid dispensing. days). Variables in PDMP data that to 2015 revealed decreased opioid We sought first to answer the require pharmacists’ input at the time prescriptions for patients 13 to 22 question of whether the downward of dispensing include 11,15 years old. Single-state Medicaid trends in opioid prescribing seen in prescribed, quantity prescribed, and data for children 2 to 17 years old studies using data from EDs or using days’ supply. PDMP data do not revealed a decline from 17 opioid claims data from subsets of children include the indications for analgesic prescriptions per 1000 on the basis of insurance type hold for prescriptions.

Downloaded from www.aappublications.org/news by guest on September 30, 2021 2 BASCO et al Included Outcomes and if the mean daily MME dispensed We built a product file on the basis of The rate outcome corresponds to an changed over the same years. the National Drug Code (NDC) of all indicator defined by the CDC in the drug products dispensed 2010–2017 context of their Prescription Drug RESULTS that fall under SCRIPTS reporting Overdose Prevention for States From the first quarter of 2010 to the using both Centers for Disease surveillance program, and the end of the fourth quarter of 2017, Control and Prevention (CDC) Opioid definitions, drugs used in calculation, there were 630 004 prescriptions Overdose Indicator Support Toolkit and population denominators chosen for opioid analgesics dispensed to and Red Book sources to add data are intended to allow comparison of children 0 to 18 years old. This fields needed for analysis.17,18 The the indicators across counties within corresponded to a quarterly rate of 17 study list excluded opioid analgesics a state and among states. The CDC- 18.68 prescriptions per 1000 not typically used by outpatient defined indicators apply to all ages. residents 0 to 18 years old in quarter children, such as hospital- The first outcome of interest was 1 of 2010, declining to 12.03 in administered opioids, , the prescription opioid-dispensing quarter 4 of 2017, a 35.6% decline and cough and cold preparations frequency, calculated quarterly as over the 8 calendar years (P , .001; as recommended by the CDC.17 the number of observed dispensing Fig 1, Supplemental Table 2). Propoxyphene was excluded from all events divided by the age-referenced When looking at differences by age, analyses because it was withdrawn US census population estimates for dispensed opioid prescription rate for from the market in 2010. the state, producing a rate of opioid infantsaged0to12monthsincreased was excluded because it was not analgesic prescriptions per 1000 17 during the years studied from 10 per consistently reported to the South state residents per quarter. For 1000 population to 14 per 1000 (P , Carolina PDMP until it was evaluating changes over time by age .01), with similar statistically significant reclassified as a Schedule IV group, we calculated dispensed prescription rates per year, first for all increases among children up to age 8 controlled substance in August P , children aged 0 to 18, then by 1-year years (all values .05, Table 1). 2014. Conducting analyses for both Post hoc assessment of the drugs outcomes with and without Tramadol age strata across the 8 calendar years of data available. The denominator dispensed revealed that, beginning in revealed no clinically meaningful 2014, there was a marked increase in differences. After identification of for this calculation was the mid-year census estimate of the South Carolina the appearance of acetaminophen- opioid products of interest using combination products NDCs, we used data from the CDC child population for the respective calendar year. in the data. From the period of and Red Book sources to identify 2010–2013 to 2014–2017, the following for each drug product: The second outcome of interest was acetaminophen-hydrocodone generic name, strength per unit, the mean daily MME per dispensed combination products-dispensing unit of measure, MME conversion prescription, calculated by using the events (not rate) increased by .700% factor, opioid (yes or no), opioid following formula: daily MME = for children 0 to 4 years old and fi classi cation, and US Drug strength per unit 3 quantity 3 MME .350% for children 5 to 9 years old. Enforcement Administration conversion factor / days’ supply. Acetaminophen-hydrocodone 17–19 Class. NDCs formed a many- Analyses describe the sample, the combination products also increased as into-one grouping with each unique annual rate of dispensed opioid a share of opioids dispensed from product name in SCRIPTS. A single analgesic prescriptions for all children 24.6% of the opioids dispensed to NDC from each grouping was selected aged 0 to 18 years, then for each 1- children 0 to 4 years old in 2010–2013 to cross-reference selected fields in year age stratum, per year. Because of to 70.6% of the opioids dispensed to the online Red Book file and the 2017 evident differences in the trajectory of children 0 to 4 years old in 2010–2013, CDC MME conversion file to ensure therateoutcomebasedonage,wealso accompanied by a large percentage accuracy of the product name and conducted post hoc analyses by age increase among 5- to 9-year-old children newly added fields. The CDC MME grouped 0 to 8 years old and 9 to 18 (Supplemental Table 3). For ages 9 to conversion file was the primary source years old. For the daily MME outcome, 18, however, there was an annual to obtain the strength per unit, unit of we prespecified age groupings of 0 to decline in dispensed opioid measure, and MME conversion factor 4,5to9,10to14,and15to18 prescriptions, with each 1-year group for each opioid product.19 The use of years. We used univariate generalized reaching its lowest level in 2017. The these data was approved by the South linear regression (accounting for largest declines were among those aged Carolina DHEC, and the institutional autocorrelation) to determine if the 12 to 18 years, who experienced review board at our institution rate of opioid analgesic dispensing had declines of 32% to 41% over the 8 years deemed this not human research. declined significantly from 2010 to 2017 studied (all P values , .05; Table 1). Age

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 147, number 3, March 2021 3 and reveals that the greatest decline in daily MME occurred among infants and children 0 to 4 years old. In addition, the daily MME dispensed from 2010 to 2013 varied considerably from year to year among children 0 to 4 years old, in some years reaching daily MME equal to the daily MME of children 10 to 14 years old. However, by 2014, the year-to-year variability in the mean daily MME became less pronounced and was comparatively much lower for children 0 to 4 than for the older age groupings. Among children aged 10 to 14 and 15 to 18 years, there was little change in mean daily MME over the years studied.

FIGURE 1 DISCUSSION Number and quarterly rate of opioid analgesics dispensed per 1000 state residents 0 to 18 years The number of ambulatory opioid old, South Carolina PDMP data, 2010–2017. Rates are expressed as the number of prescriptions dispensed to children in the age group of interest per quarter per 1000 mid-year US Census Bureau analgesic prescriptions dispensed to population of children in the referenced age group. The table portion includes rates among all children 0 to 18 years old in South children 0 to 18 years old. Q, quarter. Carolina declined significantly between the first quarter of 2010 and the last quarter of 2017, with was positively associated with rate, 18 years old, from 40.7 daily MMEs in the largest declines among teenagers. regardless of calendar year (Table 1). 2010 to 37.6 daily MMEs in 2017 Consistent with previous research, (generalized linear regression, P , the rate of dispensed opioid From 2010 to 2017, the mean daily .001). Figure 2 displays the mean prescriptions was positively MME dispensed per prescription daily MME of dispensed prescriptions correlated with patient age.14,20,21 declined by 7.6% among children 0 to by calendar year and by age group Although a decrease in overall rate of opioid prescriptions dispensed TABLE 1 Annual Rates of Opioid Analgesics Dispensed per 1000 State Residents by 1-Year Age Strata, 0–18 Years Old, South Carolina PDMP Data, 2010–2017 to children is encouraging, that observation is coupled with only Age Group 2010 2011 2012 2013 2014 2015 2016 2017 Change P a minimal decline in the mean daily 0–12 mo 10 9 9 9 12 10 14 14 Increasing .02 MME dispensed, and the majority of 13–24 mo 3 3 2 3 9 7 9 10 Increasing ,.01 the decline in MME per day was seen 25–36 mo 2 2 2 2 8 7 7 6 Increasing ,.01 3 y 2 1 2 2 9 7 8 7 Increasing .02 among those 0 to 9 years old. 4 y 3 2 2 3 10 9 10 8 Increasing .01 There are many factors that likely 5 y 3 2 3 2 11 10 11 10 Increasing ,.01 6 y 4 3 3 5 12 12 14 12 Increasing ,.01 contribute to the decline in the rate 7 y 7 5 5 5 14 14 14 14 Increasing .01 of dispensed opioid prescriptions 8 y 10 9 9 9 17 16 16 14 Increasing .03 during the study period. Although our 9 y 20 17 15 15 22 18 20 17 No change .68 study was not designed as a time- 10 y 28 32 25 23 30 28 25 22 No change .18 series analysis, there were increasing 11 y 43 41 42 37 40 36 34 28 Decreasing ,.01 12 y 65 65 60 59 57 50 49 39 Decreasing ,.001 reports about the adverse effects 13 y 89 87 87 80 82 69 63 53 Decreasing ,.001 of opioids on children throughout 14 y 122 127 119 115 104 97 86 72 Decreasing ,.001 the 2000s, and states instituted 15 y 176 177 173 156 155 132 127 112 Decreasing ,.001 increasingly robust PDMPs during the 16 y 228 237 227 217 207 184 169 155 Decreasing ,.001 22–24 , same years. In 2012 and 2013, 17 y 302 299 294 278 267 228 219 186 Decreasing .001 fi 18 y 325 333 318 299 278 248 215 191 Decreasing ,.001 speci c warnings against using All children 78 78 75 70 71 63 60 52 Decreasing ,.001 codeine for control included a US Rates are expressed as the number of prescriptions dispensed to children in the age group of interest per year per 1000 Food and Drug Administration mid-year US Census Bureau population of children in the referenced age group. (FDA)–issued black box warning

Downloaded from www.aappublications.org/news by guest on September 30, 2021 4 BASCO et al FIGURE 2 Mean daily MME of opioid analgesics dispensed per prescription, by age group, South Carolina PDMP, 2010–2017. Data source: South Carolina DHEC; received: July 18, 2018. against the use of codeine post- Department of Health and Human obtained by using a large administrative tonsillectomy because of the Services for all Schedule II–Schedule database revealed that children heightened risk of respiratory IV controlled substance prescriptions. receiving 30 to 59 daily MME experiencedanadjustedoddsof among children who We found that the mean daily MME overdose of 1.18 (95% confidence rapidly metabolize the prodrug dispensed decreased by only 7.6% interval: 1.05–1.31) compared with (codeine) to the active molecule during the study years, and the decline 25,26 subjects receiving ,30 daily MME.13 (morphine). Robust PDMP in mean daily MME occurred primarily There are also building data that programs are associated with in children ,10 years old, with little 27 nonsteroidal anti-inflammatory agents decreased opioid prescribing. change among those 12 to 18 years old fi can be as effective as opioids Speci c to South Carolina, in 2016, (Fig 2). Without diagnostic data, it is postprocedure.29–33 Therefore, even if some private insurers began not possible to know whether the opioids are prescribed for appropriate requiring that providers check the mean daily MME dispensed was indications such as posttrauma or PDMP database before prescribing appropriate or why it changed less for postoperative pain, providers should opioids and other controlled the children older than 9 years, but the focus on appropriate daily MME dosing substances for durations of .5 days mean values in these dispensed for children to reduce adverse events and at 3-month intervals for any prescriptions were near the CDC- and reduce the amount of unused opioid patient who received long-term suggested threshold of 50 MME per doses in homes and communities. controlled substances, quickly day,apointabovewhichpatientsmay followed by similar requirements experience increased risk of adverse The finding of temporal increases in mandated by the South Carolina events.28 Data from 2009 to 2017 dispensed opioids among children aged

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 147, number 3, March 2021 5 0 to 8 years was unexpected and not All pediatric providers should focus increase in dispensing among children consistent with other published data on opioid stewardship. Human aged 0 to 8 years difficult to interpret. on opioid prescribing rates in younger epidemiology studies have revealed The days’ supply variable is entered by children, although those studies did not a relationship between adolescent the pharmacist at dispensing, and use PDMP data and excluded children opioid exposure and enhanced risk for pharmacists may have to estimate days’ aged ,2years.11,12,14 In post hoc development of a substance use supply on the basis of frequency noted analyses of the specific compounds disorder in adulthood,34,35 with on a prescription and the number of appearing in the database, the previous medical use of opioids noted doses on the prescription if specific increased dispensed opioid rate among as a risk factor for progression to days’ supply data are not included children0to8yearsoldwasdriven opioid misuse and addiction.10,36 by the prescriber. We also do not know primarily by increased dispensing of However, risk for prolonged use, how many of the drugs were prescribed acetaminophen-hydrocodone misuse, and abuse is variable among to be taken on a scheduled versus as- combination products and, to a lesser adolescents, so exposure to opioids needed basis, so we do not know if the extent, hydrochloride. alone does not appear to be the sole patients actually were intended to Although acetaminophen-codeine driver of opioid misuse after childhood receive the calculated mean daily MME. combination products declined and adolescence.37–41 Therefore, Provider type and treatment setting, between 2010–2013 and 2014–2017, clinical decisions regarding opioid missing from these data, are also as might be expected because of the prescribing during childhood and important in devising stewardship FDA action, the absolute decline of adolescence should be made cautiously, efforts because other studies have acetaminophen-codeine combination weighing individually conferred risks revealed that provider type (eg, “non- product dispensing was eclipsed against potential benefits of use.9,42 pediatrician”)andlocation(eg,ED by increases in acetaminophen- versus ambulatory) are associated with hydrocodone combination product One strength of this study is that different rates of opioid prescribing.12,44 dispensing (Supplemental Table 3). the findings represent a broad, There are several possible temporal population-based estimate for a single CONCLUSIONS explanations for this shift. Tramadol state, evaluating dispensed opioid Therateofopioidanalgesic became a controlled substance in analgesic prescriptions regardless of prescriptions dispensed to children 2014, perhaps leading to substitution location of care or source of payment, 0 to 18 years old in South Carolina of acetaminophen-hydrocodone including opioids paid for in cash. declined by 35.6% overall between combination products for Tramadol. In Nevertheless, the study has several 2010 and 2017, and the slope of the addition, the FDA rule changes for limitations. The data are from a single decline suggests that the rate will codeine-containing products may have southern state, and pediatric opioid- continue to decrease. However, the also pushed providers to use more dispensing data reveal regional mean daily MME dispensed declined acetaminophen-hydrocodone variability.15 The population minimally during the same time frame, combination products. There were denominator was the mid-year census suggesting that more can be done to no changes in the availability of population for the respective year and improve responsible opioid liquid hydrocodone preparations or agegroup.Censusdatahavebeen prescribing and dispensing. changes in FDA indications for revealed to undercount children, hydrocodone during these years, and particularly young children, a fact that its schedule changed from III to II would bias our estimated rates toward ABBREVIATIONS 43 just after the change in Tramadol being higher than actual rates. CDC: Centers for Disease Control schedule. Nevertheless, it is possible However, the dispensed opioid rates and Prevention that providers saw acetaminophen- were so much lower among subjects DHEC: Department of Health and hydrocodone combination products 0to8yearsoldthan9to18yearsold Environmental Control as the most logical alternative, that underestimating the young ED: emergency department givenrestrictionsoncodeineand child denominator would not FDA: US Food and Drug Tramadol prescribing. The fact substantially alter the rate trend among Administration that acetaminophen-hydrocodone all children. Because the study MME: morphine milligram equivalent combination products composed excluded opioid-containing cough and NDC: National Drug Code .70% of opioids dispensed to cold , the rate outcome PDMP: prescription drug monitor- children0to4yearsoldbetween undercounts total opioid-dispensing ing program 2014 and 2017 may also explain the events. However, the CDC indicators SCRIPTS: South Carolina Reporting large reduction in variability of mean focus on analgesic preparations. The & Identification Tracking daily MME after 2014 seen among absence of indication data makes System subjects 0 to 4 years old (Fig 2). interpretation of the unexpected

Downloaded from www.aappublications.org/news by guest on September 30, 2021 6 BASCO et al PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2021 by the American Academy of Pediatrics FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: Supported by a contract from the South Carolina Department of Health and Environmental Control and in part by the National Institutes of Health National Center for Advancing Translational Sciences through grant UL1 TR001450, the National Institute on Drug Abuse through grant K23 DA036566, and the Centers for Disease Control and Prevention Prescription Drug Overdose Prevention for States Program through grant U17CD002730. Funded by the National Institutes of Health (NIH). POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

REFERENCES 1. Hedegaard HM, Warner M, Miniño AM. 9. Coffin P, Banta-Green C. The dueling 2012–2017. N Engl J Med. 2019;380(11): Drug Overdose Deaths in the United obligations of opioid stewardship. Ann 1043–1052 States, 1999–2017. In: NCHS Data Brief. Intern Med. 2014;160(3):207 17. Centers for Disease Control and 2018:1–8 10. Miech R, Johnston L, O’Malley PM, Keyes Prevention. CDC’s 2. Feder KA, Letourneau EJ, Brook J. KM, Heard K. Prescription opioids in Indicator Support Toolkit: Guidance for Children in the opioid epidemic: adolescence and future opioid misuse. Building and Reporting on Opioid- addressing the next generation’s public Pediatrics. 2015;136(5). Available at: Related Mortality, Morbidity, and PDMP health crisis. Pediatrics. 2019;143(1): www.pediatrics.org/cgi/content/full/ Indicators. Atlanta, GA: Centers for e20181656 136/5/e1169 Disease Control and Prevention; 2018 3. Gaither JR, Shabanova V, Leventhal JM. 11. Kaiser SV, Asteria-Penaloza R, 18. IBM Micromedex RED BOOK. US national trends in pediatric deaths Vittinghoff E, Rosenbluth G, Cabana MD, International business machines. from prescription and illicit opioids, Bardach NS. National patterns of Available at: https://www.ibm.com/us- 1999–2016. JAMA Netw Open. 2018;1(8): codeine prescriptions for children in en/marketplace/micromedex-red-book. e186558 the emergency department. Pediatrics. Accessed July 24, 2019 2014;133(5). Available at: www. 4. Winkelman TNA, Villapiano N, 19. Centers for Disease Control and pediatrics.org/cgi/content/full/133/5/ Kozhimannil KB, Davis MM, Patrick SW. Prevention; National Center for Injury e1139 Incidence and costs of neonatal Prevention and Control. CDC abstinence syndrome among infants 12. Meckler GD, Sheridan DC, Charlesworth Compilation of Benzodiazepines, Muscle with Medicaid: 2004–2014. Pediatrics. CJ, Lupulescu-Mann N, Kim H, Sun BC. Relaxants, , Zolpidem, and 2018;141(4):e20173520 Opioid prescribing practices for Opioid Analgesics with Oral Morphine pediatric . J Pediatr. 2019;204: Milligram Equivalent Conversion 5. Gaither JR, Leventhal JM, Ryan SA, 240–244.e2 Factors, 2017 Version. Atlanta, GA: Camenga DR. National trends in Centers for Disease Control and hospitalizations for opioid poisonings 13. Chua KP, Brummett CM, Conti RM, Prevention; 2017 among children and adolescents, 1997 Bohnert A. Association of opioid to 2012. JAMA Pediatr. 2016;170(12): prescribing patterns with prescription 20. Van Winkle PJ, Ghobadi A, Chen Q, 1195–1201 opioid overdose in adolescents and Menchine M, Sharp AL. Association of young adults. JAMA Pediatr. 2020; age and opioid use for adolescents and 6. Kane JM, Colvin JD, Bartlett AH, Hall M. 174(2):141–148 young adults in community emergency Opioid-related critical care resource departments. Am J Emerg Med. 2019; use in US children’s hospitals. 14. Chung CP, Callahan ST, Cooper WO, et al. 37(8):1397–1403 [published correction appears in Outpatient opioid prescriptions for Pediatrics. 2018;141(6):e20180935]. children and opioid-related adverse 21. Tomaszewski DM, Arbuckle C, Yang S, Pediatrics. 2018;141(4):e20173335 events. Pediatrics. 2018;142(2): Linstead E. Trends in opioid use in e20172156 pediatric patients in US emergency 7. Curtin SC, Tejada-Vera B, Warmer M. departments from 2006 to 2015. JAMA Drug overdose deaths among 15. Hudgins JD, Porter JJ, Monuteaux MC, Netw Open. 2018;1(8):e186161 adolescents aged 15–19 in the United Bourgeois FT. Trends in opioid States: 1999–2015. NCHS Data Brief. prescribing for adolescents and 22. Ciszkowski C, Madadi P, Phillips MS, 2017;(282):1–8 young adults in ambulatory care Lauwers AE, Koren G. Codeine, settings. Pediatrics. 2019;143(6): ultrarapid- genotype, and 8. Seth P, Scholl L, Rudd RA, Bacon S. e20181578 postoperative death. N Engl J Med. Overdose deaths involving opioids, 2009;361(8):827–828 , and psychostimulants - United 16. Zhu W, Chernew ME, Sherry TB, Maestas States, 2015–2016. MMWR Morb Mortal N. Initial opioid prescriptions among US 23. Bailey JE, Campagna E, Dart RC; RADARS Wkly Rep. 2018;67(12):349–358 commercially insured patients, System Poison Center Investigators. The

Downloaded from www.aappublications.org/news by guest on September 30, 2021 PEDIATRICS Volume 147, number 3, March 2021 7 underrecognized toll of prescription in children: a randomized trial. CMAJ. subsequent abuse of prescription opioid abuse on young children. Ann 2014;186(18):1358–1363 opioids in young adults. J Adolesc – – Emerg Med. 2009;53(4):419 424 31. Walrave Y, Maschi C, Bailleux S, et al. Health. 2013;52(2):158 163 24. Meyer D, Tobias JD. Adverse effects Pain after tonsillectomy: effectiveness 38. Groenewald C, Palermo T. Legitimate following the inadvertent of current guidelines? Eur Arch opioid prescription increases the risk administration of opioids to infants and Otorhinolaryngol. 2018;275(1):281–286 for future opioid misuse in some children. Clin Pediatr (Phila). 2005; 32. Sobieraj DM, Martinez BK, Miao B, et al. adolescents. Evid Based Nurs. 2016; 44(6):499–503 Comparative effectiveness of analgesics 19(3):83 25. Kuehn BM. FDA: No codeine after to reduce acute pain in the prehospital 39. Osborne V, Serdarevic M, Crooke H, tonsillectomy for children. JAMA. 2013; setting. Prehosp Emerg Care. 2020; Striley C, Cottler LB. Non-medical opioid – 309(11):1100 24(2):163 174 use in youth: gender differences in risk 33. Zhu A, Benzon HA, Anderson TA. factors and prevalence. Addict Behav. 26. Kelly LE, Rieder M, van den Anker J, Evidence for the efficacy of systemic 2017;72:114–119 et al. More codeine fatalities after opioid-sparing analgesics in pediatric tonsillectomy in North American 40. Schepis TS, Wilens TE, McCabe SE. surgical populations: a systematic children. Pediatrics. 2012;129(5). Prescription drug misuse: sources of review. Anesth Analg. 2017;125(5): Available at: www.pediatrics.org/cgi/ controlled medications in adolescents. 1569–1587 content/full/129/5/e1343 J Am Acad Child Adolesc Psychiatry. 34. McCabe SE, Schulenberg JE, O’Malley 2019;58(7):670–680.e4 27. Haffajee RL, Mello MM, Zhang F, PM, Patrick ME, Kloska DD. Non-medical Zaslavsky AM, Larochelle MR, Wharam 41. Yang S, Werner BC. Risk factors for use of prescription opioids during the JF. Four states with robust prescription prolonged postoperative opioid use transition to adulthood: a multi-cohort drug monitoring programs reduced after spinal fusion for adolescent national longitudinal study. Addiction. opioid dosages. Health Aff (Millwood). idiopathic scoliosis. J Pediatr Orthop. 2014;109(1):102–110 2018;37(6):964–974 2019;39(10):500–504 35. McCabe SE, Veliz PT, Boyd CJ, Schepis 28. Dowell D, Haegerich TM, Chou R. CDC TS, McCabe VV, Schulenberg JE. A 42. Thienprayoon R, Porter K, Tate M, Ashby fi guideline for prescribing opioids for prospective study of nonmedical use of M, Meyer M. Risk strati cation for - United States, 2016. prescription opioids during opioid misuse in children, adolescents, [published correction appears in adolescence and subsequent substance and young adults: a quality MMWR Recomm Rep. 2016;65(11):295]. use disorder symptoms in early midlife. improvement project. Pediatrics. 2017; – MMWR Recomm Rep. 2016;65(1):1 49 Drug Depend. 2019;194:377–385 139(1):e20160258 29. Poonai N, Datoo N, Ali S, et al. Oral 36. McCabe SE, West BT, Veliz P, McCabe VV, 43. O’Hare WP. The Undercount of Young morphine versus Stoddard SA, Boyd CJ. Trends in Children in the US Decennial Census, administered at home for postoperative medical and nonmedical use of 1st ed. New York, NY: Springer Briefs in orthopedic pain in children: prescription opioids among US Population Series, Springer a randomized controlled trial. CMAJ. adolescents: 1976–2015. Pediatrics. International; 2015 2017;189(40):E1252–E1258 2017;139(4):e20162387 44. Phang KG, Roberts JR, Ebeling M, 30. Poonai N, Bhullar G, Lin K, et al. Oral 37. Fiellin LE, Tetrault JM, Becker WC, Fiellin Garner SS, Basco WT Jr.. Opioids or administration of morphine versus DA, Hoff RA. Previous use of alcohol, steroids for or . ibuprofen to manage postfracture pain cigarettes, and marijuana and Pediatrics. 2020;146(2):e20193690

Downloaded from www.aappublications.org/news by guest on September 30, 2021 8 BASCO et al Trends in Dispensed Opioid Analgesic Prescriptions to Children in South Carolina: 2010−2017 William T. Basco Jr, Jenna L. McCauley, Jingwen Zhang, Patrick D. Mauldin, Kit N. Simpson, Khosrow Heidari, Justin E. Marsden and Sarah J. Ball Pediatrics originally published online February 1, 2021;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2021/01/28/peds.2 020-0649 References This article cites 35 articles, 11 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2021/01/28/peds.2 020-0649#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): http://www.aappublications.org/cgi/collection/pharmacology_sub Public Health http://www.aappublications.org/cgi/collection/public_health_sub Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on September 30, 2021 Trends in Dispensed Opioid Analgesic Prescriptions to Children in South Carolina: 2010−2017 William T. Basco Jr, Jenna L. McCauley, Jingwen Zhang, Patrick D. Mauldin, Kit N. Simpson, Khosrow Heidari, Justin E. Marsden and Sarah J. Ball Pediatrics originally published online February 1, 2021;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2021/01/28/peds.2020-0649

Data Supplement at: http://pediatrics.aappublications.org/content/suppl/2021/01/29/peds.2020-0649.DCSupplemental

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2021 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on September 30, 2021