Document resource
Opioids are one of the most effective therapies for treating cancer-associated pain in many patients. However, the safety and effectiveness vary between individual patients. Part of the variability is attributable to genetic variability. There are several genes that may be involved, but the strongest evidence supports the role of CYP2D6. Hepatic CYP2D6 is implicated due to its role in activating several opioids to metabolites that are more active opioid receptor agonists. The strongest evidence for CYP2D6 is for tramadol and codeine; however, hydrocodone and oxycodone are also metabolized to more active metabolites. In addition to the genetic variants, concurrent medications that inhibit CYP2D6 activity are also implicated in opioid response. Considering that evidence, clinical pharmacogenetic prescribing guidelines are published by organizations including the National Comprehensive Cancer Network (NCCN) for adult patients with cancer pain and the Clinical Pharmacogenetic Implementation Consortium (CPIC) to guide opioid therapy. The implementation of these guidelines are expected to improve pain control and reduce the side effects caused by opioid therapy.The presentation will discuss the evidence supporting the role of CYP2D6 pharmacogenetics in opioid therapies. The pharmacologic aspects underlying the contribution of CYP2D6 opioid response variability will be presented. Recent clinical trial and real-world evidence will be highlighted. Gaps in evidence and challenges in implementation studies will be described to guide future research needs. Collectively, the presentation will highlight the evidence and the opportunities to use pharmacogenetics to improve the safety and effectiveness of opioid therapies.