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Genet Med. 2019 Jan 23. doi: 10.1038/s41436-018-0431-8. [Epub ahead of print]

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial.

Author information

1
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
2
Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA.
3
Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA.
4
Division of General Internal Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
5
Department of Health Policy and Management, Indiana University, Indianapolis, IN, USA.
6
Department of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
7
University of Florida Health Pathology Laboratories, Gainesville, FL, USA.
8
Department of Pathology, Immunology & Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, USA.
9
Department of Community Dentistry and Behavioral Science, College of Dentistry, Gainesville, FL, USA.
10
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA. lcavallari@cop.ufl.edu.
11
Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USA. lcavallari@cop.ufl.edu.
12
Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA. lcavallari@cop.ufl.edu.

Abstract

PURPOSE:

CYP2D6 bioactivates codeine and tramadol, with intermediate and poor metabolizers (IMs and PMs) expected to have impaired analgesia. This pragmatic proof-of-concept trial tested the effects of CYP2D6-guided opioid prescribing on pain control.

METHODS:

Participants with chronic pain (94% on an opioid) from seven clinics were enrolled into CYP2D6-guided (n = 235) or usual care (n = 135) arms using a cluster design. CYP2D6 phenotypes were assigned based on genotype and CYP2D6 inhibitor use, with recommendations for opioid prescribing made in the CYP2D6-guided arm. Pain was assessed at baseline and 3 months using PROMIS® measures.

RESULTS:

On stepwise multiple linear regression, the primary outcome of composite pain intensity (composite of current pain and worst and average pain in the past week) among IM/PMs initially prescribed tramadol/codeine (n = 45) had greater improvement in the CYP2D6-guided versus usual care arm (-1.01 ± 1.59 vs. -0.40 ± 1.20; adj P = 0.016); 24% of CYP2D6-guided versus 0% of usual care participants reported ≥30% (clinically meaningful) reduction in the composite outcome. In contrast, among normal metabolizers prescribed tramadol or codeine at baseline, there was no difference in the change in composite pain intensity at 3 months between CYP2D6-guided (-0.61 ± 1.39) and usual care (-0.54 ± 1.69) groups (adj P = 0.540).

CONCLUSION:

These data support the potential benefits of CYP2D6-guided pain management.

KEYWORDS:

CYP2D6; chronic pain; opioids; pharmacogenetics; precision medicine

PMID:
30670877
DOI:
10.1038/s41436-018-0431-8

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