TY - JOUR
T1 - Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
AU - IGNITE Pharmacogenetics Working Group
AU - Ramsey, Laura B.
AU - Ong, Henry H.
AU - Schildcrout, Jonathan S.
AU - Shi, Yaping
AU - Tang, Leigh Anne
AU - Hicks, J. Kevin
AU - El Rouby, Nihal
AU - Cavallari, Larisa H.
AU - Tuteja, Sony
AU - Aquilante, Christina L.
AU - Beitelshees, Amber L.
AU - Lemkin, Daniel L.
AU - Blake, Kathryn V.
AU - Williams, Helen
AU - Cimino, James J.
AU - Davis, Brittney H.
AU - Limdi, Nita A.
AU - Empey, Philip E.
AU - Horvat, Christopher M.
AU - Kao, David P.
AU - Lipori, Gloria P.
AU - Rosenman, Marc B.
AU - Skaar, Todd C.
AU - Teal, Evgenia
AU - Winterstein, Almut G.
AU - Owusu Obeng, Aniwaa
AU - Salyakina, Daria
AU - Gupta, Apeksha
AU - Gruber, Joshua
AU - McCafferty-Fernandez, Jennifer
AU - Bishop, Jeffrey R.
AU - Rivers, Zach
AU - Benner, Ashley
AU - Tamraz, Bani
AU - Long-Boyle, Janel
AU - Peterson, Josh F.
AU - Van Driest, Sara L.
N1 - Publisher Copyright:
© 2020 American Medical Association. All rights reserved.
PY - 2020/12/14
Y1 - 2020/12/14
N2 - 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 10629 per 100000 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 100000 children). Among commonly prescribed opioids, annual prevalence per 100000 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 100000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100000 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.
AB - 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 10629 per 100000 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 100000 children). Among commonly prescribed opioids, annual prevalence per 100000 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 100000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100000 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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U2 - 10.1001/jamanetworkopen.2020.29411
DO - 10.1001/jamanetworkopen.2020.29411
M3 - Article
C2 - 33315113
AN - SCOPUS:85098531769
SN - 2574-3805
VL - 3
JO - JAMA Network Open
JF - JAMA Network Open
IS - 12
M1 - e2029411
ER -