title: Pharmacogenetics for Safe Codeine Use in Sickle Cell Disease.
abstract: After postoperative deaths in children who were prescribed codeine, several pediatric hospitals have removed it from their formularies. These deaths were attributed to atypical cytochrome P450 2D6 (CYP2D6) pharmacogenetics, which is also implicated in poor analgesic response. Because codeine is often prescribed to patients with sickle cell disease and is now the only Schedule III opioid analgesic in the United States, we implemented a precision medicine approach to safely maintain codeine as an option for pain control. Here we describe the implementation of pharmacogenetics-based codeine prescribing that accounts for CYP2D6 metabolizer status. Clinical decision support was implemented within the electronic health record to guide prescribing of codeine with the goal of preventing its use after tonsillectomy or adenoidectomy and in CYP2D6 ultra-rapid and poor metabolizer (high-risk) genotypes. As of June 2015, CYP2D6 genotype results had been reported for 2468 unique patients. Of the 830 patients with sickle cell disease, 621 (75%) had a CYP2D6 genotype result; 7.1% were ultra-rapid or possible ultra-rapid metabolizers, and 1.4% were poor metabolizers. Interruptive alerts recommended against codeine for patients with high-risk CYP2D6 status. None of the patients with an ultra-rapid or poor metabolizer genotype were prescribed codeine. Using genetics to tailor analgesic prescribing retained an important therapeutic option by limiting codeine use to patients who could safely receive and benefit from it. Our efforts represent an evidence-based, innovative medication safety strategy to prevent adverse drug events, which is a model for the use of pharmacogenetics to optimize drug therapy in specialized pediatric populations.
authors.affiliation: Departments of Pharmaceutical Sciences.
authors.forename: Roseann S
authors.initials: RS
authors.lastname: Gammal
authors.affiliation: Departments of Pharmaceutical Sciences, kristine.crews@stjude.org.
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Crews
authors.affiliation: Departments of Pharmaceutical Sciences.
authors.forename: Cyrine E
authors.initials: CE
authors.lastname: Haidar
authors.affiliation: Departments of Pharmaceutical Sciences.
authors.forename: James M
authors.initials: JM
authors.lastname: Hoffman
authors.affiliation: Departments of Pharmaceutical Sciences.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Baker
authors.affiliation: Departments of Pharmaceutical Sciences.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Barker
authors.affiliation: Hematology, and.
authors.forename: Jeremie H
authors.initials: JH
authors.lastname: Estepp
authors.affiliation: Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee; and.
authors.forename: Deqing
authors.initials: D
authors.lastname: Pei
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Broeckel
authors.affiliation: Hematology, and.
authors.forename: Winfred
authors.initials: W
authors.lastname: Wang
authors.affiliation: Hematology, and.
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Weiss
authors.affiliation: Departments of Pharmaceutical Sciences.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Relling
authors.affiliation: Hematology, and.
authors.forename: Jane
authors.initials: J
authors.lastname: Hankins
mesh_terms: D000233:Adenoidectomy; D000293:Adolescent; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D000066491:Clinical Decision-Making / Q000379:methods*; D003061:Codeine / Q000627:therapeutic use*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D020000:Decision Support Systems, Clinical; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy; D010641:Phenotype; D010818:Practice Patterns, Physicians'; D013714:Tennessee; D014068:Tonsillectomy
chemical_list: D000701:Analgesics, Opioid; D005819:Genetic Markers; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine