{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T11:13:24Z","timestamp":1793445204608,"version":"4.5.0"},"reference-count":36,"publisher":"The Pediatric Pharmacy Association","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>\n          <jats:bold>OBJECTIVES:<\/jats:bold> To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study.<\/jats:p>\n        <jats:p>\n          <jats:bold>METHODS:<\/jats:bold> Medications prescribed for \u22651% PICU patients (age &lt; 18 years) in 2010 were identified from 39 children's hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA).<\/jats:p>\n        <jats:p>\n          <jats:bold>RESULTS:<\/jats:bold> A total of 66,896 patients received \u22651 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2\u20136) unique drugs per patient were used off-label. Those who received \u22651 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p &lt; 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA\/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone.<\/jats:p>\n        <jats:p>\n          <jats:bold>CONCLUSIONS:<\/jats:bold> Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.<\/jats:p>","DOI":"10.5863\/1551-6776-20.3.186","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T19:49:09Z","timestamp":1603828149000},"page":"186-196","source":"Crossref","is-referenced-by-count":8,"title":["Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research"],"prefix":"10.5863","volume":"20","author":[{"given":"Angela S.","family":"Czaja","sequence":"first","affiliation":[{"name":"Division of Critical Care, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado"},{"name":"Critical Care, Children's Hospital Colorado, Aurora, Colorado"},{"name":"Center for Pharmaceutical Outcomes Research, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela D.","family":"Reiter","sequence":"additional","affiliation":[{"name":"Critical Care, Children's Hospital Colorado, Aurora, Colorado"},{"name":"Clinical Pharmacy, Children's Hospital Colorado, Aurora, Colorado"},{"name":"Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Lynn","family":"Schultz","sequence":"additional","affiliation":[{"name":"Clinical Informatics, Children's Hospital Colorado, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Valuck","sequence":"additional","affiliation":[{"name":"Center for Pharmaceutical Outcomes Research, Aurora, Colorado"},{"name":"Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3883","reference":[{"issue":"1","key":"i1551-6776-20-3-186-b1","series-title":"FDA Consum","first-page":"12","article-title":"Drug research and children","volume":"37","year":"2003","unstructured":"Meadows\n              M.\n            \n          \n          Drug research and children. FDA Consum. 2003;37(1):12\u201317."},{"issue":"2","key":"i1551-6776-20-3-186-b2","series-title":"Pediatrics","first-page":"285","article-title":"Pediatric versus adult drug trials for conditions with high pediatric disease burden","volume":"130","year":"2012","unstructured":"Bourgeois\n              FT, \n            \n              Murthy\n              S, \n            \n              Pinto\n              C\n            , \n          et al. Pediatric versus adult drug trials for conditions with high pediatric disease burden. Pediatrics. 2012;130(2):285\u2013292."},{"issue":"1 pt 1","key":"i1551-6776-20-3-186-b3","series-title":"Pediatrics","first-page":"181","article-title":"Uses of drugs not described in the package insert (off-label uses)","volume":"110","year":"2002","unstructured":"Committee on Drugs, American Academy of Pediatrics\n          . Uses of drugs not described in the package insert (off-label uses). Pediatrics. 2002;110(1 pt 1):181\u2013183."},{"issue":"18","key":"i1551-6776-20-3-186-b4","series-title":"JAMA","first-page":"1914","article-title":"Pediatric information in drug product labeling","volume":"307","year":"2012","unstructured":"Sachs\n              AN, \n            \n              Avant\n              D, \n            \n              Lee\n              CS\n            , \n          et al. Pediatric information in drug product labeling. JAMA. 2012;307(18):1914\u20131915."},{"issue":"1","key":"i1551-6776-20-3-186-b5","series-title":"Fundam Clin Pharmacol","first-page":"125","article-title":"Unlicensed and off-label uses of drugs in paediatrics: a review of the literature","volume":"17","year":"2003","unstructured":"Cuzzolin\n              L, \n            \n              Zaccaron\n              A, \n            \n              Fanos\n              V.\n            \n          \n          Unlicensed and off-label uses of drugs in paediatrics: a review of the literature. Fundam Clin Pharmacol. 2003;17(1):125\u2013131."},{"issue":"9","key":"i1551-6776-20-3-186-b6","series-title":"Eur J Pediatr","first-page":"552","article-title":"A literature review on off-label drug use in children","volume":"164","year":"2005","unstructured":"Pandolfini\n              C, \n            \n              Bonati\n              M.\n            \n          \n          A literature review on off-label drug use in children. Eur J Pediatr. 2005;164(9):552\u2013558."},{"issue":"5","key":"i1551-6776-20-3-186-b7","series-title":"Paediatr Drugs","first-page":"323","article-title":"Pharmacotherapy in pediatric critical illness: a prospective observational study","volume":"11","year":"2009","unstructured":"McDonnell\n              C, \n            \n              Hum\n              S, \n            \n              Frndova\n              H, \n            \n              Parshuram\n              CS.\n            \n          \n          Pharmacotherapy in pediatric critical illness: a prospective observational study. Paediatr Drugs. 2009;11(5):323\u2013331."},{"issue":"11","key":"i1551-6776-20-3-186-b8","series-title":"J Clin Pharmacol","first-page":"1305","article-title":"Drug utilization in the pediatric intensive care unit: monitoring prescribing trends and establishing prioritization of pharmacotherapeutic evaluation of critically ill children","volume":"45","year":"2005","unstructured":"Zuppa\n              AF, \n            \n              Adamson\n              PC, \n            \n              Mondick\n              JT\n            , \n          et al. Drug utilization in the pediatric intensive care unit: monitoring prescribing trends and establishing prioritization of pharmacotherapeutic evaluation of critically ill children. J Clin Pharmacol. 2005;45(11):1305\u20131312."},{"issue":"12","key":"i1551-6776-20-3-186-b9","series-title":"Can J Anaesth","first-page":"1078","article-title":"Off-label drug use in pediatric anesthesia and intensive care according to official and pediatric reference formularies","volume":"57","year":"2010","unstructured":"Doherty\n              DR, \n            \n              Pascuet\n              E, \n            \n              Ni\n              A, \n            \n              Stewart\n              P\n            , \n          et al. Off-label drug use in pediatric anesthesia and intensive care according to official and pediatric reference formularies. Can J Anaesth. 2010;57(12):1078\u20131088."},{"issue":"5","key":"i1551-6776-20-3-186-b10","series-title":"Pediatr Crit Care Med","first-page":"e195","article-title":"Food and Drug Administration approval for medications used in the pediatric intensive care unit: a continuing conundrum","volume":"12","year":"2011","unstructured":"Yang\n              CP, \n            \n              Veltri\n              MA, \n            \n              Anton\n              B\n            , \n          et al. Food and Drug Administration approval for medications used in the pediatric intensive care unit: a continuing conundrum. Pediatr Crit Care Med. 2011;12(5):e195\u2013e199."},{"issue":"7","key":"i1551-6776-20-3-186-b11","series-title":"WMJ","first-page":"343","article-title":"Off-label medication use in an academic hospital pediatric critical care unit","volume":"108","year":"2009","unstructured":"Hsu\n              B, \n            \n              Brazelton\n              T.\n            \n          \n          Off-label medication use in an academic hospital pediatric critical care unit. WMJ. 2009;108(7):343\u2013348."},{"issue":"9000","key":"i1551-6776-20-3-186-b12","series-title":"Lancet","first-page":"549","article-title":"Use of \u201coff-label\u201d and unlicensed drugs in paediatric intensive care unit","volume":"347","year":"1996","unstructured":"Turner\n              S, \n            \n              Gill\n              A, \n            \n              Nunn\n              T\n            , \n          et al. Use of \u201coff-label\u201d and unlicensed drugs in paediatric intensive care unit. Lancet. 1996;347(9000):549\u2013550."},{"issue":"11","key":"i1551-6776-20-3-186-b13","series-title":"Am J Health Syst Pharm","first-page":"1062","article-title":"Evaluating the off-label use of medications in children","volume":"63","year":"2006","unstructured":"Eiland\n              LS, \n            \n              Knight\n              P.\n            \n          \n          Evaluating the off-label use of medications in children. Am J Health Syst Pharm. 2006;63(11):1062\u20131065."},{"issue":"1 pt 2","key":"i1551-6776-20-3-186-b14","series-title":"Pediatrics","first-page":"205","article-title":"Pediatric deaths attributable to complex chronic conditions: a population-based study of Washington State, 1980\u20131997","volume":"106","year":"2000","unstructured":"Feudtner\n              C, \n            \n              Christakis\n              DA, \n            \n              Connell\n              FA.\n            \n          \n          Pediatric deaths attributable to complex chronic conditions: a population-based study of Washington State, 1980\u20131997. Pediatrics. 2000;106(1 pt 2):205\u2013209."},{"issue":"4","key":"i1551-6776-20-3-186-b15","series-title":"Pediatrics","first-page":"647","article-title":"Children with complex chronic conditions in inpatient hospital settings in the United States","volume":"126","year":"2010","unstructured":"Simon\n              TD, \n            \n              Berry\n              J, \n            \n              Feudtner\n              C\n            , \n          et al. Children with complex chronic conditions in inpatient hospital settings in the United States. Pediatrics. 2010;126(4):647\u2013655."},{"issue":"5","key":"i1551-6776-20-3-186-b16","series-title":"J Pediatr","first-page":"595","article-title":"Importance of organ dysfunction in determining hospital outcomes in children","volume":"144","year":"2004","unstructured":"Johnston\n              JA, \n            \n              Yi\n              MS, \n            \n              Britto\n              MT, \n            \n              Mrus\n              JM.\n            \n          \n          Importance of organ dysfunction in determining hospital outcomes in children. J Pediatr. 2004;144(5):595\u2013601."},{"issue":"3","key":"i1551-6776-20-3-186-b17","series-title":"Pediatrics","first-page":"849","article-title":"Readmission and late mortality after pediatric severe sepsis","volume":"123","year":"2009","unstructured":"Czaja\n              AS, \n            \n              Zimmerman\n              JJ, \n            \n              Nathens\n              AB.\n            \n          \n          Readmission and late mortality after pediatric severe sepsis. Pediatrics. 2009;123(3):849\u2013857."},{"key":"i1551-6776-20-3-186-b18","article-title":"Drug Information Website","unstructured":"US Food and Drug Administration\n          . Drug Information Website. Drugs@FDA. http:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/index.cfm. Accessed May 2013."},{"key":"i1551-6776-20-3-186-b19","article-title":"List of High-Alert Medication","unstructured":"Institue for Safe Medication Practices\n          . List of High-Alert Medication. http:\/\/www.ismp.org\/Tools\/institutionalhighAlert.asp. Accessed June 6, 2013."},{"key":"i1551-6776-20-3-186-b20","article-title":"BPCA Priority List of Pediatric Therapeutic Needs","unstructured":"BPCA Priority List of Pediatric Therapeutic Needs. http:\/\/bpca.nichd.nih.gov\/prioritization\/status.cfm. Accessed June 6, 2013."},{"issue":"1","key":"i1551-6776-20-3-186-b21","series-title":"Int J Epidemiol","first-page":"158","article-title":"Principles of multilevel modelling","volume":"29","year":"2000","unstructured":"Greenland\n              S.\n            \n          \n          Principles of multilevel modelling. Int J Epidemiol. 2000;29(1):158\u2013167."},{"issue":"22","key":"i1551-6776-20-3-186-b22","series-title":"Arch Intern Med","first-page":"2554","article-title":"Positive outcomes through the appropriate use of off-label prescribing","volume":"166","year":"2006","unstructured":"Bright\n              JL.\n            \n          \n          Positive outcomes through the appropriate use of off-label prescribing. Arch Intern Med. 2006;166(22):2554\u20132555; author reply 2555."},{"issue":"1","key":"i1551-6776-20-3-186-b23","series-title":"Drugs","first-page":"57","article-title":"Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension","volume":"67","year":"2007","unstructured":"Leibovitch\n              L, \n            \n              Matok\n              I, \n            \n              Paret\n              G.\n            \n          \n          Therapeutic applications of sildenafil citrate in the management of paediatric pulmonary hypertension. Drugs. 2007;67(1):57\u201373."},{"issue":"3","key":"i1551-6776-20-3-186-b24","series-title":"Pediatrics","first-page":"530","article-title":"Improving pediatric dosing through pediatric initiatives: what we have learned","volume":"121","year":"2008","unstructured":"Rodriguez\n              W, \n            \n              Selen\n              A, \n            \n              Avant\n              D\n            , \n          et al. Improving pediatric dosing through pediatric initiatives: what we have learned. Pediatrics. 2008;121(3):530\u2013539."},{"issue":"3","key":"i1551-6776-20-3-186-b25","series-title":"Arch Dis Child","first-page":"305","article-title":"Association between licence status and medication errors","volume":"96","year":"2011","unstructured":"Conroy\n              S.\n            \n          \n          Association between licence status and medication errors. Arch Dis Child. 2011;96(3):305\u2013306."},{"issue":"13","key":"i1551-6776-20-3-186-b26","series-title":"Drug Saf","first-page":"1059","article-title":"The impact of unlicensed and off-label drug use on adverse drug reactions in paediatric patients","volume":"27","year":"2004","unstructured":"Neubert\n              A, \n            \n              Dormann\n              H, \n            \n              Weiss\n              J\n            , \n          et al. The impact of unlicensed and off-label drug use on adverse drug reactions in paediatric patients. Drug Saf. 2004;27(13):1059\u20131067."},{"issue":"9","key":"i1551-6776-20-3-186-b27","series-title":"Acta Paediatr","first-page":"965","article-title":"Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study","volume":"88","year":"1999","unstructured":"Turner\n              S, \n            \n              Nunn\n              AJ, \n            \n              Fielding\n              K, \n            \n              Choonara\n              I.\n            \n          \n          Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study. Acta Paediatr. 1999;88(9):965\u2013968."},{"issue":"4","key":"i1551-6776-20-3-186-b28","series-title":"Crit Care Med","first-page":"1317","article-title":"Prospective evaluation of sedation-related adverse events in pediatric patients ventilated for acute respiratory failure","volume":"40","year":"2012","unstructured":"Grant\n              MJ, \n            \n              Scoppettuolo\n              LA, \n            \n              Wypij\n              D, \n            \n              Curley\n              MA.\n            \n          \n          Prospective evaluation of sedation-related adverse events in pediatric patients ventilated for acute respiratory failure. Crit Care Med. 2012;40(4):1317\u20131323."},{"issue":"3","key":"i1551-6776-20-3-186-b29","series-title":"Crit Care Clin","first-page":"593","article-title":"Delirium: an emerging frontier in the management of critically ill children","volume":"25","year":"2009","unstructured":"Smith\n              HA, \n            \n              Fuchs\n              DC, \n            \n              Pandharipande\n              PP\n            , \n          et al. Delirium: an emerging frontier in the management of critically ill children. Crit Care Clin. 2009;25(3):593\u2013614, x."},{"issue":"1","key":"i1551-6776-20-3-186-b30","series-title":"Paediatr Drugs","first-page":"45","article-title":"The National Institutes of Health and the Best Pharmaceuticals for Children Act","volume":"11","year":"2009","unstructured":"Zajicek\n              A.\n            \n          \n          The National Institutes of Health and the Best Pharmaceuticals for Children Act. Paediatr Drugs. 2009;11(1):45\u201347."},{"issue":"7","key":"i1551-6776-20-3-186-b31","series-title":"JAMA","first-page":"905","article-title":"Pediatric drug labeling: improving the safety and efficacy of pediatric therapies","volume":"290","year":"2003","unstructured":"Roberts\n              R, \n            \n              Rodriguez\n              W, \n            \n              Murphy\n              D, \n            \n              Crescenzi\n              T.\n            \n          \n          Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA. 2003;290(7):905\u2013911."},{"issue":"6","key":"i1551-6776-20-3-186-b32","series-title":"Clin Ther","first-page":"808","article-title":"Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications","volume":"35","year":"2013","unstructured":"Dimasi\n              JA.\n            \n          \n          Innovating by developing new uses of already-approved drugs: trends in the marketing approval of supplemental indications. Clin Ther. 2013;35(6):808\u2013818."},{"key":"i1551-6776-20-3-186-b33","article-title":"Pediatric Trials Network","unstructured":"Pediatric Trials Network. https:\/\/pediatric-trials.org\/. Accessed June 6, 2013."},{"issue":"suppl 6","key":"i1551-6776-20-3-186-b34","series-title":"Crit Care Med","first-page":"S83","article-title":"Adverse drug events in intensive care units: risk factors, impact, and the role of team care","volume":"38","year":"2010","unstructured":"Kane-Gill\n              SL, \n            \n              Jacobi\n              J, \n            \n              Rothschild\n              JM.\n            \n          \n          Adverse drug events in intensive care units: risk factors, impact, and the role of team care. Crit Care Med. 2010;38(suppl 6):S83\u2013S89."},{"issue":"3","key":"i1551-6776-20-3-186-b35","series-title":"Clin Pediatr (Phila)","first-page":"208","article-title":"Parental preferences for FDA-approved medications prescribed for their children","volume":"50","year":"2011","unstructured":"Yoon\n              EY, \n            \n              Clark\n              SJ, \n            \n              Butchart\n              A\n            , \n          et al. Parental preferences for FDA-approved medications prescribed for their children. Clin Pediatr (Phila). 2011;50(3):208\u2013214."},{"issue":"2","key":"i1551-6776-20-3-186-b36","series-title":"Eur J Clin Pharmacol","first-page":"141","article-title":"Children's views on unlicensed\/off-label paediatric prescribing and paediatric clinical trials","volume":"68","year":"2012","unstructured":"Mukattash\n              T, \n            \n              Trew\n              K, \n            \n              Hawwa\n              AF, \n            \n              McElnay\n              JC.\n            \n          \n          Children's views on unlicensed\/off-label paediatric prescribing and paediatric clinical trials. Eur J Clin Pharmacol. 2012;68(2):141\u2013148."}],"container-title":["The Journal of Pediatric Pharmacology and Therapeutics"],"original-title":[],"link":[{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/20\/3\/article-p186.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/meridian.allenpress.com\/jppt\/article-pdf\/20\/3\/186\/1786598\/1551-6776-20_3_186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/20\/3\/article-p186.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/20\/3\/article-p186.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:37:25Z","timestamp":1747355845000},"score":1,"resource":{"primary":{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/20\/3\/article-p186.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015]]},"references-count":36,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.5863\/1551-6776-20.3.186","relation":{},"ISSN":["1551-6776"],"issn-type":[{"value":"1551-6776","type":"print"}],"subject":[],"published":{"date-parts":[[2015]]}}}