A service improvement project to review prescribing information provided by general practitioners for new referrals to a UK National Health Service hospital pain clinic: potential implications of CYP2D6 enzyme inhibition

Abstract

Introduction: Chronic pain is often managed using co-prescription of analgesics and adjuvants, with concomitant medication prescribed for comorbidities. Patients may have suboptimal response to some analgesics or be at risk of drug interactions or adverse drug reactions (ADRs) due to polypharmacy affecting CYP2D6 enzyme activity. The aim of the service improvement project was to determine the proportion of patients referred to a specialist pain service in the UK National Health Service (NHS) by general practitioners (GPs) who may be at risk of suboptimal analgesic response or ADRs due to CYP2D6 inhibition through polypharmacy. This was achieved by reviewing clinical prescribing information provided by GPs at time of referral. It was hoped that the findings could be used to aid clinical and prescribing decisions without conducting CYP2D6 genotyping or phenotyping. Methods: A review of letters from 250 patients referred to an NHS hospital pain service from GPs over a 3-month period was undertaken. Information about current and concomitant medications was analysed to identify the potential for CYP2D6 inhibition and adverse events. Results: Letters failed to provide information about current pain medication for 20 (8%) patients or non-pain concomitant medication for 54 (21.6%) patients. Of 176 patients, 52 (29.5%) patients with information about non-pain concomitant medication had been prescribed at least one known CYP2D6 inhibitor. A total of 35 (19.9%) patients were identified as being at risk of an adverse drug reaction and 33 (18.75%) patients at risk of suboptimal analgesic response due to co-administration of CYP2D6 inhibitors. Conclusion:The review revealed the need for improved detail in GP referral letters used to transfer care to UK NHS hospital pain clinics. There is a need to consider an individual's CYP2D6 phenotype when prescribing analgesic prodrugs to manage persistent pain. Caution is needed when patients are co-prescribed codeine or tramadol with selective serotonin reuptake inhibitors (SSRIs).

CYP2D6-guided opioid therapy improves pain control in CYP2D6 intermediate and poor metabolizers: a pragmatic clinical trial

“…Phenoconversion is likely common, as data indicate approximately 20–30% of patients treated for pain are prescribed a CYP2D6 inhibitor. 18,19…”

A Single Site Population Study to Investigate CYP2D6 Phenotype of Patients with Persistent Non-Malignant Pain

“…At enrolment, 59% of our sample had been prescribed analgesics dependent on CYP2D6 activity such as co-codamol and tramadol, a similar percentage to a recent service improvement project that reviewed prescribing information provided by general practitioners (GP) for new referrals to a UK National Health Service hospital pain clinic [37]. Prescribers are advised to review medication within 2–4 weeks after titration to identify patients that are unlikely to respond [51], although in our sample 70% of participants reported that they had previously failed to respond to one or more CYP2D6 analgesics despite still consuming such medication.…”

“…However, CYP2D6 screening is not part of current clinical practice. We previously reported that 19.9% of patients referred by primary care physicians to a secondary care specialist pain management clinic were at risk of drug interactions associated with co-prescription of analgesic prodrugs reliant on CYP2D6 and CYP2D6 inhibitors [37]. A method of inferring phenotype without the need for genotyping is needed at the point of care.…”

Personalised medicine and medicines optimisation

“…This issue of the British Journal of Pain ( BJP ) includes a service evaluation by Johnson et al 1 which identified that 8% of referral letters did not even contain information about current analgesics and 20% did not contain information about other medicines. Around a one-fifth of patients were at risk of suboptimal analgesic response or developing side effects due to interaction with other medicines metabolised by the CYP450 2D6 isoenzyme.…”