Starting April 6, 2015, University of Florida Health Pathology Laboratories, in collaboration with the UF Health Personalized Medicine Program, will offer CYP2D6 genetic testing. CYP2D6 genotype has important relevance for response to codeine and tramadol and possibly hydrocodone and oxycodone, which depends on CYP2D6 for bioactivation. CYP2D6 genotype may also have relevance for additional drugs metabolized by the CYP2D6 pathway.
Approximately five to 10 percent of patients have a genotype leading to no CYP2D6 activity and are referred to as poor metabolizers (PMs). PMs cannot metabolize codeine or tramadol into their more active forms (morphine or O-desmethyltramadol, respectively) and, therefore, have insufficient pain relief from codeine- or tramadol-containing analgesics. At the other end of the spectrum, another five percent of patients have too much CYP2D6 activity and are referred to as ultrarapid metabolizers (UMs). UMs quickly convert codeine or tramadol to their more active compounds, which can lead to toxic opioid levels with usual drug doses. Hydrocodone and oxycodone are also metabolized to more active forms by CYP2D6, but the impact of genetic variability on these agents is less clear.
Additional drugs metabolized by the CYP2D6 pathway include SSRIs (e.g., paroxetine), SNRIs (e.g., venlafaxine), TCAs (e.g., nortriptyline), and other psychiatric medications (e.g., aripiprazole). Consultation with a clinical pharmacist is recommended if the results indicate an abnormal CYP2D6 genotype and assistance is needed with interpretation and/or therapeutic options.
For questions on testing and interpretation, call or e-mail:
- UF Health Pathology Laboratories: 352.265.9900 (email@example.com)
- UF Health Personalized Medicine Program: 352.380.1441 (firstname.lastname@example.org)
This test could be collected as either a buccal or blood sample. Blood is preferable but buccal will suffice if it is in the best interest of the patient. Both will return the same accuracy of results.
- Blood: Purple-top tube 3 mL (1 mL minimum)
- Buccal: Four brushes
Genotype and phenotype with a detailed report will be available in Epic in the lab result section. The projected turnaround-time is 7 – 10 days.
Interpretation of Results
Based on genotype, persons are classified by their phenotype as follows:
- Extensive metabolizer (EM)
- Intermediate metabolizer (IM)
- Poor metabolizer (PM)
- Ultra-rapid metabolizer (UM)
- Extensive metabolizer (EM) to ultra-rapid metabolizer (UM)
- Intermediate metabolizer (IM) to extensive metabolizer (EM)
- Crews KR, Gaedigk A, Dunnenberger HM, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for Cytochrome P450 2D6 Genotype and Codeine Therapy: 2014 Update.Clinical Pharmacology and Therapeutics. 2014;95(4):376-382. doi:10.1038/clpt.2013.254.