Faculty Collaboration Database

Pharmacogenetics for Safe Codeine Use in Sickle Cell Disease. Pediatrics 2016 Jul;138(1)

Date

06/24/2016

Pubmed ID

27335380

Pubmed Central ID

PMC4925073

DOI

10.1542/peds.2015-3479

Scopus ID

2-s2.0-84976869634 (requires institutional sign-in at Scopus site)   81 Citations

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.

Author List

Gammal RS, Crews KR, Haidar CE, Hoffman JM, Baker DK, Barker PJ, Estepp JH, Pei D, Broeckel U, Wang W, Weiss MJ, Relling MV, Hankins J

Author

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenoidectomy
Adolescent
Analgesics, Opioid
Anemia, Sickle Cell
Child
Child, Preschool
Clinical Decision-Making
Codeine
Cytochrome P-450 CYP2D6
Decision Support Systems, Clinical
Female
Genetic Markers
Genotype
Genotyping Techniques
Humans
Infant
Male
Pain, Postoperative
Phenotype
Practice Patterns, Physicians'
Tennessee
Tonsillectomy