Does pharmacogenomics have a role in opioid prescribing?
An article written by Dr. Aaron K Wong
Pharmacogenomics is an increasingly important and effective method used to guide objective, safe, and effective personalised prescribing. The term ‘pharmacogenomics’ refers to the impact of multigene variations in DNA and RNA on drug response. Personalised prescribing has revolutionised treatments in the past decade, allowing clinicians to maximise drug efficacy and minimise adverse effects based on a person’s genetic profile. We recently reviewed the potential of pharmacogenomics to improve the effective use of opioids within the palliative care population. [1] Opioids, the gold standard for cancer pain relief, are among the commonest medications prescribed in palliative care practice.
In the advanced cancer population where the prognosis is short, there is little time to waste experiencing unnecessary morbidity from side effects. An experimental approach to prescribing for pain is particularly undesirable. A personalised treatment plan is critical in this setting. A simple blood or saliva genetic test that could determine the strong likelihood of clinical benefit or adverse effects from a certain opioid would help to significantly improve patient pain and symptom outcomes.
Pharmacogenomic evidence guiding opioid prescribing is currently available for codeine and tramadol, which relates to the drug metabolising enzyme CYP2D6 gene variants. There are two drug-gene pairs (codeine-CYP2D6 and tramadol-CYP2D6), which consist of clinically actionable variants with strong recommendations to guide/alter prescribing. However, these medications are less commonly prescribed for pain in palliative care. Research is accelerating with other opioids, including oxycodone (CYP2D6) and methadone (CYP2B6, ABCB1). Further effects have also been observed for opioid transporters, receptors, signal transduction pathways, and neurotransmitter enzymes.
For example, OPRM1 (opioid receptor) and COMT (neurotransmitter enzyme) are receiving increasing attention and have implications for all opioids. OPRM1 has a functional variant (rs1799971), most commonly found in East Asians (e.g. Japanese, Chinese, and Koreans) (49%), which is associated with increases in morphine requirements. COMT has a functional variant (rs4680), which leads to a three- to four-fold reduction in COMT enzyme activity, leading to greater dopamine levels, and is associated with favourable analgesic response to opioid use, and variations in pain perception. These and other gene variants that may contribute to opioid response are currently being studied but more work is needed to clinically validate any associations and to inform prescribing. Current evidence indicates that the incorporation of pharmacogenomic testing into opioid prescribing practice should focus on the CYP2D6 gene and its actionable variants.
Although opioid pharmacogenomic tests are not widely used in clinical practice, decreasing costs and rapid turnover means greater accessibility and affordability for patients.
With increasing research and clinical potential, it is likely that pharmacogenomic parameters will provide clinicians with upfront confidence in deciding which opioids to preference or avoid, and reassurance on the speed at which these opioids may be titrated to deliver optimal analgesia as quickly as possible. This could mitigate the need for switching between multiple potentially ineffective or intolerable opioids, thus reducing suffering, time, and healthcare costs.
Palliative care, like other areas of medicine, will increasingly influence and be influenced by this body of science. The challenge for those working at the intersection of palliative care and pharmacogenomics is to ensure key findings that influence practice are communicated in a manner that are readily accessible to clinicians as they navigate this emerging area of care.
References
- Wong AK, Somogyi AA, Rubio J, Philip J. The Role of Pharmacogenomics in Opioid Prescribing. Curr Treat Options Oncol. 2022 Oct;23(10):1353-1369. doi: 10.1007/s11864-022-01010-x. Epub 2022 Aug 24.
Dr. Aaron K Wong | MBBS, BMedSci, FRACP, FAChPM, GCertClinTeach
Palliative Medicine Physician & Medical Oncologist
Clinical Trials Lead, Palliative Care | Peter MacCallum Cancer Centre & The Royal Melbourne Hospital
NHMRC Postgraduate PhD Scholar (Opioid Pharmacogenomics) | University of Melbourne