Narabayashi, M., Saijo, Y., Takenoshita, S., Chida, M., Shimoyama, N., Miura, T., … Advisory Committee for Oxycodone Study. (2008). Opioid rotation from oral morphine to oral oxycodone in cancer patients with intolerable adverse effects: An open-label trial. Japanese Journal of Clinical Oncology, 38(4), 296–304.

To investigate the efficacy and safety of switching from oral morphine to oral oxycodone and to evaluate this regimen in patients with renal impairment

Patients were rotated from controlled-release (CR) oral morphine to oral oxycodone CR via a 3:2 ratio. Immediate-release (IR) oxycodone was used for breakthrough pain (BTP) at 1/6 of the 24-hour oxycodone dose. If pain intensity was rated as moderate to severe or if more than 3 rescue doses of IR oxycodone were administered in 24 hours, oxycodone was titrated upward. If untoward side effects were experienced, the oxycodone dose was titrated downward. Patients were deemed successful if pain control was adequate for 10 days. Pharmacokinetic evaluation for renal impairment was conducted on patients with adequate relief.

• The sample consisted of 25 patients.
• Mean age was 62.8 years (SD = 11.6 years).
• The sample was 24% female and 76% male.
• Cancer diagnoses included lung, breast, and pancreas.
• All patients were receiving morphine for cancer pain and were either having difficulty controlling pain with morphine or had intolerable side effects.

This study was a multisite, outpatient setting study conducted at 14 sites in Japan.

This was a multicenter, open label, dose-titration study.

• Pain control rate (i.e., the rate in which patients achieved stable and adequate pain control) was defined as CR oxycodone unchanged for 48 hours or more, slight or no pain intensity, fewer than two rescue doses in 24 hours, and tolerable side effects.
• A 0–100 mm pain intensity visual analog scale (VAS) was used with every administration. 
• Categorical acceptability was rated on a scale from 1 (very poor) to 5 (excellent).
• Safety was evaluated based on frequency, severity, seriousness, causality, and tolerability of adverse events.
• Serum creatinine and creatinine clearance were measured.

• The study yielded an adequate pain control rate of 84%, and time to adequate relief was 2.3 days.
• Pain intensity at study entry was 1.9 (moderate pain). Intensity significantly decreased by the end of the study (p < 0.0001).
• Average VAS went from 53.5 mm at study entry to 27.6 mm at study end (p < 0.0001).
• Acceptability was rated as very poor (12%) to poor (64%) at the beginning of the study. At end, acceptability was rated as very poor (8.3%), poor (16.7%), fair (45.8%), and good (29.2%). Mean acceptability was 2.1 at entry and 3.0 at end (p = 0.0004).
• Nausea was rated 2.3 with morphine and decreased to 0.4 with oxycodone (p = 0.0005), drowsiness went from 2.1 to 0.9 (p = 0.0313), vomiting went from 2.2 to 0.2, and constipation went from 2.2 to 1.6.
• M3G and M6G metabolites were increased at study initiation in patients with renal compromise; oxycodone metabolites were not increased in patients with renal compromise at the end of the study.

Rotation to oral oxycodone for patients who had inadequate pain control or significant adverse events with morphine was successful. Retention of oxycodone metabolites did not seem to exist in patients with renal compromise.

• The sample size was small, with fewer than 30 patients.
• The sample was not randomized, there was no control, and it was a convenience sample.
• Assessment for adverse events was subjective.

Oxycodone can be recommended as an alternative to morphine, and patients may experience fewer adverse events with oxycodone. Patients with renal compromise may benefit from oxycodone over morphine as morphine contributes to metabolite accumulation, leading to potential oversedation or adverse events.