Drug–Drug Interactions Associated with Introduction of Oxycodone for Management of Cancer-Related Pain in Hospitalized Patients

Dear Editor:

Cancer-related pain is one of the most frequent symptoms in cancer patients. It is reported in 30% to 50% of patients undergoing cancer treatment and in >70% of patients with advanced cancer. ¹ Oxycodone is widely used to manage cancer-related pain because of its rapid analgesic effect and tolerability, ² and is mainly metabolized by cytochrome P450 (CYP) through CYP3A4 and CYP2D6. ³ The number of elderly patients with cancer is currently rising due to an increase in the aging population. As a result, drug–drug interactions (DDIs) occur increasingly often among these patients, as they are concomitantly prescribed drugs to treat multiple comorbidities. Therefore, we surveyed potential DDIs during the introduction of oral oxycodone to treat cancer pain in hospitalized patients.

We reviewed 236 cancer patients who first received oral oxycodone on hospitalization at the Tokyo Metropolitan Bokutoh Hospital between August 2018 and December 2020. The potential major DDIs between orally administered oxycodone and other prescribed drugs were determined using IBM Micromedex^® Drug Interactions (Product of IBM Watson Health). ⁴

The median age of these patients was 72 years (range 35–93 years). The median number of additional drugs administered were 8 (range 1–22). A total of 411 potential DDIs were detected. Of the 236 patients, 198 (83.9%) had at least one potential DDI. Potential DDIs relating to CYP were the inhibition of oxycodone metabolism through CYP3A4 in 44 cases (9.4%) and induction of oxycodone metabolism through CYP3A4 in 29 cases (6.2%). Among the drugs causing potential DDIs, prochlorperazine was the most used concomitantly in 127 cases (27.2%), followed by metoclopramide in 41 cases (8.6%) and zolpidem in 39 cases (8.4%) (Table 1).

We found that the prevalence of potential DDIs of oral oxycodone with other concomitantly administered drugs was 83.9%. A previous study suggested that the prevalence of potential DDIs identified with Micromedex was 61.3% in elderly cancer patients, and that 23% of the DDIs were opioid related. ⁵ Among the 411 cases, the prevalence of potential DDIs through CYP was only 15.8%. The majority of DDIs occurred due to pharmacodynamic interactions. In our study, because potential DDIs were assessed at the time of oxycodone introduction, the high prescription of prochlorperazine and metoclopramide for nausea and vomiting may contribute to the high prevalence of potential DDIs. Potential DDIs that may cause increased central nervous system depression were identified in 88 cases (18.8%) in which concomitant medications included zolpidem, tramadol, pregabalin, trazodone, and lorazepam. These drugs are frequently prescribed to patients with advanced cancer; unlike prochlorperazine and metoclopramide, a longer duration of opioid use may increase potential DDIs. We aim to evaluate the relationship between the duration of oral oxycodone use and DDIs in the future.

To the best of our knowledge, this is the first report to find a high potential prevalence of DDIs at the time of oxycodone therapy on admission. The incidence of adverse events associated with DDIs may be higher in clinical practice. Future studies should assess the impact of DDIs due to oxycodone on clinical outcomes.