CPIC authors respond to CYP2D6–codeine clinical perspective article

Published: June 1st, 2015

Category: Stories

The Clinical Pharmacogenetics Implementation Consortium (CPIC) published guidelines for use of codeine in patients with variable CYP2D6 metabolism in January 2014. These guidelines recommended a codeine alternative in CYP2D6 ultrarapid and poor metabolizers. Guideline authors recently responded1 to a February 2015 perspective article in which Formea and Nicholson2 raised questions about the clinical use of these guidelines.

In their response, authors emphasized the role of CPIC guidelines in clinical practice, noting that they serve to provide guidance to clinicians on interpreting and applying genetic test results to optimize therapy. Authors also addressed Formea and Nicholas’ concerns about the need to “step up” patients with CYP2D6 genetic variability to medications usually used for severe pain. CPIC authors noted that the guideline is “recommending these alternatives for the minority of the population with a pharmacogenetic profile that poses them at risk of therapeutic failure or adverse effects. It is exactly these patients who may require step 3 analgesics.“ Authors further noted that the clinical challenges associated with use of more potent opioid agents should not prevent clinicians from pursuing optimal pain management strategies in at-risk CYP2D6 patients.

Clinical Implications

Thoughtful conversations such as these among clinicians and researchers are essential to inform the future use of pharmacogenetic data in routine clinical practice. As clinical use of pharmacogenetic data becomes more commonplace, there will be an increasing need for insight on strategies for applying guideline recommendations to clinical practice.

Find out more about the clinical effects of pharmacogenetic variability for codeine and other drugs through the PharmGKB and CPIC guidelines.


  1. Crews et al. Considerations for the utility of the CPIC guideline for CYP2D6 genotype and codeine therapy [Letter]. Clin Chem. 2015;61:775-6.
  2. Nicholson WT et al. Clinical perspective on the Clinical Pharmacogenetics Implementation Consortium updated 2014 guidelines for CYP2D6 and codeine. Clin Chem. 2015;61:319-21.