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author Ramsey, Laura B.
Ong, Henry H.
Schildcrout, Jonathan S.
Shi, Yaping
Tang, Leigh Anne
Hicks, J. Kevin
El Rouby, Nihal
Cavallari, Larisa H.
Tuteja, Sony
Aquilante, Christina L.
Beitelshees, Amber L.
Lemkin, Daniel L.
Blake, Kathryn V.
Williams, Helen
Cimino, James J.
Davis, Brittney H.
Limdi, Nita A.
Empey, Philip E.
Horvat, Christopher M.
Kao, David P.
Lipori, Gloria P.
Rosenman, Marc B.
Skaar, Todd C.
Teal, Evgenia
Winterstein, Almut G.
Owusu Obeng, Aniwaa
Salyakina, Daria
Gupta, Apeksha
Gruber, Joshua
McCafferty-Fernandez, Jennifer
Bishop, Jeffrey R.
Rivers, Zach
Benner, Ashley
Tamraz, Bani
Long-Boyle, Janel
Peterson, Josh F.
Van Driest, Sara L.
author_facet Ramsey, Laura B.
Ong, Henry H.
Schildcrout, Jonathan S.
Shi, Yaping
Tang, Leigh Anne
Hicks, J. Kevin
El Rouby, Nihal
Cavallari, Larisa H.
Tuteja, Sony
Aquilante, Christina L.
Beitelshees, Amber L.
Lemkin, Daniel L.
Blake, Kathryn V.
Williams, Helen
Cimino, James J.
Davis, Brittney H.
Limdi, Nita A.
Empey, Philip E.
Horvat, Christopher M.
Kao, David P.
Lipori, Gloria P.
Rosenman, Marc B.
Skaar, Todd C.
Teal, Evgenia
Winterstein, Almut G.
Owusu Obeng, Aniwaa
Salyakina, Daria
Gupta, Apeksha
Gruber, Joshua
McCafferty-Fernandez, Jennifer
Bishop, Jeffrey R.
Rivers, Zach
Benner, Ashley
Tamraz, Bani
Long-Boyle, Janel
Peterson, Josh F.
Van Driest, Sara L.
author_sort Ramsey, Laura B.
collection PubMed
description IMPORTANCE: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. OBJECTIVE: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children’s hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. EXPOSURES: Prescription of 38 level A medications based on electronic health records. MAIN OUTCOMES AND MEASURES: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. RESULTS: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. CONCLUSIONS AND RELEVANCE: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.
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spelling pubmed-77370912020-12-17 Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients Ramsey, Laura B. Ong, Henry H. Schildcrout, Jonathan S. Shi, Yaping Tang, Leigh Anne Hicks, J. Kevin El Rouby, Nihal Cavallari, Larisa H. Tuteja, Sony Aquilante, Christina L. Beitelshees, Amber L. Lemkin, Daniel L. Blake, Kathryn V. Williams, Helen Cimino, James J. Davis, Brittney H. Limdi, Nita A. Empey, Philip E. Horvat, Christopher M. Kao, David P. Lipori, Gloria P. Rosenman, Marc B. Skaar, Todd C. Teal, Evgenia Winterstein, Almut G. Owusu Obeng, Aniwaa Salyakina, Daria Gupta, Apeksha Gruber, Joshua McCafferty-Fernandez, Jennifer Bishop, Jeffrey R. Rivers, Zach Benner, Ashley Tamraz, Bani Long-Boyle, Janel Peterson, Josh F. Van Driest, Sara L. JAMA Netw Open Original Investigation IMPORTANCE: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. OBJECTIVE: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children’s hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. EXPOSURES: Prescription of 38 level A medications based on electronic health records. MAIN OUTCOMES AND MEASURES: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. RESULTS: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. CONCLUSIONS AND RELEVANCE: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants. American Medical Association 2020-12-14 /pmc/articles/PMC7737091/ /pubmed/33315113 http://dx.doi.org/10.1001/jamanetworkopen.2020.29411 Text en Copyright 2020 Ramsey LB et al. JAMA Network Open. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Ramsey, Laura B.
Ong, Henry H.
Schildcrout, Jonathan S.
Shi, Yaping
Tang, Leigh Anne
Hicks, J. Kevin
El Rouby, Nihal
Cavallari, Larisa H.
Tuteja, Sony
Aquilante, Christina L.
Beitelshees, Amber L.
Lemkin, Daniel L.
Blake, Kathryn V.
Williams, Helen
Cimino, James J.
Davis, Brittney H.
Limdi, Nita A.
Empey, Philip E.
Horvat, Christopher M.
Kao, David P.
Lipori, Gloria P.
Rosenman, Marc B.
Skaar, Todd C.
Teal, Evgenia
Winterstein, Almut G.
Owusu Obeng, Aniwaa
Salyakina, Daria
Gupta, Apeksha
Gruber, Joshua
McCafferty-Fernandez, Jennifer
Bishop, Jeffrey R.
Rivers, Zach
Benner, Ashley
Tamraz, Bani
Long-Boyle, Janel
Peterson, Josh F.
Van Driest, Sara L.
Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
title Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
title_full Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
title_fullStr Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
title_full_unstemmed Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
title_short Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
title_sort prescribing prevalence of medications with potential genotype-guided dosing in pediatric patients
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737091/
https://www.ncbi.nlm.nih.gov/pubmed/33315113
http://dx.doi.org/10.1001/jamanetworkopen.2020.29411
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