Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy

Abstract

Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinical effect and safety of these drugs. Other genes that have been studied for their association with opioid clinical effect or adverse events include OPRM1 (mu receptor) and COMT (catechol‐O‐methyltransferase). This guideline updates and expands the 2014 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and codeine therapy and includes a summation of the evidence describing the impact of CYP2D6, OPRM1, and COMT on opioid analgesia and adverse events. We provide therapeutic recommendations for the use of CYP2D6 genotype results for prescribing codeine and tramadol and describe the limited and/or weak data for CYP2D6 and hydrocodone, oxycodone, and methadone, and for OPRM1 and COMT for clinical use.

Perioperative Pain Management and Opioid Stewardship: A Practical Guide

“…Empiric opioid selection should align with generally preferred agents, patient-specific pharmacologic needs, and the oral route of administration. Oxycodone, hydrocodone, and hydromorphone should be used preferentially due to their decreased propensities for active metabolites, accumulation in end organ dysfunction, drug-drug interactions, and histamine release (Table 9) [410][411][412][413][414]. Morphine, tramadol, and codeine are significantly metabolized to active metabolites and heavily renally eliminated, increasing the risk of adverse effects in some patient populations [410,415].…”

“…Individual patient response to preferred opioids still varies substantially. Genetic polymorphisms affecting opioid metabolism are not uncommon, so rotation to an agent utilizing an alternative metabolic pathway should be considered in patients with unexplained lack of response and/or significant intolerance (e.g., extreme nausea and vomiting with or without insufficient analgesia from oxycodone may be remedied by change to hydrocodone or hydromorphone) (Table 9) [414,418,419]. Newer opioid agonists can also be considered.…”

“…Abbreviations: CYP = cytochrome P450 enzyme superfamily, i.e., hepatic enzymes responsible for phase I metabolism. References: [178,[410][411][412]414,415,423,425,426,429,430].…”

Pharmacogenomics in cancer supportive care: key issues and future directions

“…CYP2D6 poor metabolizers are at risk of underexposure of the active metabolite and thus reduced analgesia, whereas ultrarapid metabolizers are at risk of overexposure and increased toxicity. CPIC guidelines suggest using an alternative opioid not metabolized by CYP2D6 [27]. Of note, hydrocodone and oxycodone have varying levels of CYP2D6-mediated metabolism and may be prone to PGx variation, although the data is less clear.…”

“…Of note, hydrocodone and oxycodone have varying levels of CYP2D6-mediated metabolism and may be prone to PGx variation, although the data is less clear. Pharmacodynamic based genes, such as those encoding for the mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT), may also affect opioid sensitivity and morphine equivalents required for pain relief, although guidelines suggest these are not actionable and dosing should be based on tolerability alone [27].…”