CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

Jennifer St. Sauver, Janet E Olson, Veronique Lee Roger, Wayne T. Nicholson, John L. Black, Paul Y Takahashi, Pedro Caraballo, Elizabeth J. Bell, Debra J. Jacobson, Nicholas Larson, Suzette J Bielinski

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression. Results: Overall, 257 (25% of RIGHT Protocol participants) patients received at least one opioid prescription; of these, 40 (15%) were poor metabolizers, 146 (57%) were intermediate to extensive metabolizers, and 71 (28%) were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38). After adjusting for age and sex, patients with a poor or ultrarapid phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95% CI: 1.39, 5.17; p=0.003). Conclusion: Our results suggest that >30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39% of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene–drug interactions could be substantial.

Original languageEnglish (US)
Pages (from-to)217-227
Number of pages11
JournalPharmacogenomics and Personalized Medicine
Volume10
DOIs
StatePublished - Jul 24 2017

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Cytochrome P-450 CYP2D6
Opioid Analgesics
Phenotype
Pain
Prescriptions
Hydrocodone
Oxycodone
Tramadol
Codeine
Electronic Health Records
Chi-Square Distribution
Nausea
Population
Primary Health Care
Logistic Models
Odds Ratio

Keywords

  • Adverse effects
  • CYP2D6
  • Opioid
  • Phenotype

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

@article{24f1e84820694ce3ae5cccbc159fffba,
title = "CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications",
abstract = "Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression. Results: Overall, 257 (25{\%} of RIGHT Protocol participants) patients received at least one opioid prescription; of these, 40 (15{\%}) were poor metabolizers, 146 (57{\%}) were intermediate to extensive metabolizers, and 71 (28{\%}) were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38). After adjusting for age and sex, patients with a poor or ultrarapid phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95{\%} CI: 1.39, 5.17; p=0.003). Conclusion: Our results suggest that >30{\%} of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39{\%} of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene–drug interactions could be substantial.",
keywords = "Adverse effects, CYP2D6, Opioid, Phenotype",
author = "{St. Sauver}, Jennifer and Olson, {Janet E} and Roger, {Veronique Lee} and Nicholson, {Wayne T.} and Black, {John L.} and Takahashi, {Paul Y} and Pedro Caraballo and Bell, {Elizabeth J.} and Jacobson, {Debra J.} and Nicholas Larson and Bielinski, {Suzette J}",
year = "2017",
month = "7",
day = "24",
doi = "10.2147/PGPM.S136341",
language = "English (US)",
volume = "10",
pages = "217--227",
journal = "Pharmacogenomics and Personalized Medicine",
issn = "1178-7066",
publisher = "Dove Medical Press Ltd.",

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TY - JOUR

T1 - CYP2D6 phenotypes are associated with adverse outcomes related to opioid medications

AU - St. Sauver, Jennifer

AU - Olson, Janet E

AU - Roger, Veronique Lee

AU - Nicholson, Wayne T.

AU - Black, John L.

AU - Takahashi, Paul Y

AU - Caraballo, Pedro

AU - Bell, Elizabeth J.

AU - Jacobson, Debra J.

AU - Larson, Nicholas

AU - Bielinski, Suzette J

PY - 2017/7/24

Y1 - 2017/7/24

N2 - Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression. Results: Overall, 257 (25% of RIGHT Protocol participants) patients received at least one opioid prescription; of these, 40 (15%) were poor metabolizers, 146 (57%) were intermediate to extensive metabolizers, and 71 (28%) were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38). After adjusting for age and sex, patients with a poor or ultrarapid phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95% CI: 1.39, 5.17; p=0.003). Conclusion: Our results suggest that >30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39% of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene–drug interactions could be substantial.

AB - Background: Variation in the CYP2D6 gene may affect response to opioids in both poor and ultrarapid metabolizers, but data demonstrating such associations have been mixed, and the impact of variants on toxicity-related symptoms (e.g., nausea) is unclear. Therefore, we examined the association between CYP2D6 phenotype and poor pain control or other adverse symptoms related to the use of opioids in a sample of primary care patients. Materials and methods: We identified all patients in the Mayo Clinic RIGHT Protocol who were prescribed an opioid medication between July 01, 2013 and June 30, 2015, and categorized patients into three phenotypes: poor, intermediate to extensive, or ultrarapid CYP2D6 metabolizers. We reviewed the electronic health record of these patients for indications of poor pain control or adverse symptoms related to medication use. Associations between phenotype and outcomes were assessed using Chi-square tests and logistic regression. Results: Overall, 257 (25% of RIGHT Protocol participants) patients received at least one opioid prescription; of these, 40 (15%) were poor metabolizers, 146 (57%) were intermediate to extensive metabolizers, and 71 (28%) were ultrarapid metabolizers. We removed patients that were prescribed a CYP2D6 inhibitor medication (n=38). After adjusting for age and sex, patients with a poor or ultrarapid phenotype were 2.7 times more likely to experience either poor pain control or an adverse symptom related to the prescription compared to patients with an intermediate to extensive phenotype (odds ratio: 2.68; 95% CI: 1.39, 5.17; p=0.003). Conclusion: Our results suggest that >30% of patients with a poor or ultrarapid CYP2D6 phenotype may experience an adverse outcome after being prescribed codeine, tramadol, oxycodone, or hydrocodone. These medications are frequently prescribed for pain relief, and ~39% of the US population is expected to carry one of these phenotypes, suggesting that the population-level impact of these gene–drug interactions could be substantial.

KW - Adverse effects

KW - CYP2D6

KW - Opioid

KW - Phenotype

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U2 - 10.2147/PGPM.S136341

DO - 10.2147/PGPM.S136341

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