Clinical use of CYP2D6–codeine guidelines

Published: November 15th, 2014

Category: Stories

The analgesic properties of codeine result from its activation by the CYP2D6 enzyme to morphine, which has 200-fold greater affinity for opioid receptors. The metabolism and activity of some other opioids (i.e., tramadol, hydrocodone, and oxycodone) are also affected by CYP2D6 variability. The Clinical Pharmacogenetics Implementation Consortium (CPIC) published updated guidelines for use of codeine in patients with variable CYP2D6 metabolism in January 2014. These guidelines recommended using an alternative to codeine in CYP2D6 ultrarapid and poor metabolizers.

In a perspective article published in Clinical Chemistry, Nicholson and Formea highlighted questions that may arise when applying CYP2D6–codeine guidelines to opioid drug therapy changes. Authors noted that the World Health Organization stepwise approach to pain management categorizes opioids as those commonly used for moderate pain (e.g., codeine, tramadol, hydrocodone) versus those often reserved for severe pain (e.g., morphine, oxymorphone, fentanyl, methadone, and hydromorphone). Authors wrote that in an outpatient setting, agents in this latter group are commonly reserved for severe, chronic pain in opioid-tolerant patients and many providers may not use them routinely in practice. Conversely, opioids often reserved for very severe pain in the outpatient setting may be more readily used in some acute inpatient scenarios (e.g., fentanyl during a surgical procedure). These factors may affect drug therapy choices when applying CYP2D6–codeine guidelines in practice.

Clinical Implications

As pharmacogenetic data are increasingly incorporated into the clinical decision making process, clinicians will rely on guidelines such as those available from CPIC and others to inform drug therapy changes. This article provides insight into the next logical step in implementing pharmacogenetics guidelines—integration of these guidelines into frontline clinical practice.

As medication experts, clinical pharmacists are poised to play an essential role in educating and equipping other health care providers to interpret and apply CPIC guidelines in clinical practice. Pharmacists can find out more about the clinical effects of pharmacogenetic variability for codeine and other drugs through the Pharmacogenomics KnowledgeBase, CPIC guidelines, and other clinician resources such as those offered by the American Society of Health-System Pharmacists and through the UF Health website.


Nicholson WT et al. Clinical perspective on the Clinical Pharmacogenetics Implementation Consortium updated 2014 guidelines for CYP2D6 and codeine. Clin Chem. 2014;61:2 [Epub ahead of print].

See other articles on the pharmacogenomics of pain management.