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Cancer-related pain and opioids
About 10%–15% of adults experience some chronic pain.1 The prevalence is considerably higher in certain populations like cancer, where pain affects more than two-thirds with advanced disease and one-third after curative treatment.2 Roughly one-third of ambulatory patients with solid tumours experiencing pain achieve significant pain reduction while one-fifth experience pain deterioration using conventional strategies within 1 month of initial assessment.3 Uncontrolled pain negatively affects quality of life and may reduce survival.4 Inadequate pain relief may be due to infrequent monitoring, lack of knowledge regarding opioid pharmacology, minority race, older age and pain assessment failure.3
Genetics and variability in opioid responses
Opioids are recommended for first-line treatment of moderate to severe pain. However, there is large interindividual variability in response. Data suggest pharmacogenomics may partially explain this, where genetic differences affect opioid pharmacokinetics and pharmacodynamics.5 6
Over 90% of patients have pharmacogenetic variant(s) which impact drug responses and over one-fourth a variant that may contribute to opioid response.7 The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published more than 45 drug-specific, peer-reviewed guidelines on how to best apply pharmacogenomics to guide therapy (more than a dozen relate to supportive care, including opioids).8 Integration of pharmacogenetic-guided treatment pathways can personalise drug selection in supportive oncology and help determine the magnitude of drug–drug and drug–drug–gene interactions.5 6 Table 1 summarises key genes and their clinical implications on opioid response.
Opioids and pharmacogenetics: best practices
Actionable genes: Cytochrome P450 2D6
Cytochrome P450 2D6 (CYP2D6) hepatically metabolises codeine, hydrocodone, oxycodone and tramadol to more potent metabolites: morphine, hydromorphone, oxymorphone and o-desmethyltramadol, respectively. CYP2D6 gene polymorphisms alter enzyme activity and can affect opioid response.5 6 It is expected that 8%–10% of the general population are poor metabolisers (PMs), 4%–6% ultrarapid metabolisers (UMs) and 25%–30% intermediate metabolisers (IMs) (frequencies vary depending on race/ethnicity).9 Codeine-related fatalities in children with the CYP2D6 …
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
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