Schutter, U., Grunert, S., Meyer, C., Schmidt, T., & Nolte, T. (2010). Innovative pain therapy with a fixed combination of prolonged-release oxycodone/naloxone: A large observational study under conditions of daily practice. Current Medical Research and Opinion, 26, 1377–1387.

To evaluate the safety and efficacy of combined prolonged-release (PR) oxycodone and PR naloxone for treatment of cancer-related pain in daily practice

Patients with severe chronic pain requiring strong analgesics entered a four-week observational period, during which they received PR oxycodone–PR naloxone. The physician determined dosage. Dose adjustments, comedication, rescue medication, and other treatments were also at the discretion of the physician. Follow-up visits occurred after the first week and at the end of the four-week observation. Data were gathered using interviewer-administered questionnaires.

• The sample was composed of 7,836 patients.
• Mean patient age was 65.8 years (SD = 13.6 years).
• Approximately 61% of patients were female and 39% were male.
• Of all patients, 17% had cancer; other diagnoses were musculoskeletal and nervous system disorders.
• Of all patients, 75% had been treated with opioids and 25% were opioid naive.
• Patients were treated by primary care physicians, anesthesiologists, and physicians with pain specialization.

• Multisite
• Outpatient
• Germany (6,496 sites)

Observational

• Brief Pain Inventory (BPI)
• Numeric pain rating scale, 0–100
• Bowel Function Index (BFI)
• Global rating scale (1 = very good, 5 = very bad)

• At baseline, the strongest pain score was 6.8 (SD = 1.8). That score declined to 3.9 (SD = 2.1) at the final follow-up visit (p < 0.001). A similar decline occurred in least, current, and mean pain intensity scores (p < 0.001).
• Rescue medication was prescribed to 11.5% of patients at the first visit and 9.5% at the first follow-up visit, one week later.
• Authors observed significant improvement in bowel function as measured by the BFI (p < 0.001). Improvement in bowel function was greater in those previously treated with opioids.
• Other symptoms associated with opioid use also declined.
• A total of 3,881 adverse events occurred in 1,566 patients (20% of patients).
• The most frequent adverse events were nausea, constipation, and diarrhea.
• Treatment with PR oxycodone–PR naloxone was discontinued in 1,157 patients (14.8%) because of adverse events or lack of efficacy.
• At the third follow-up visit, 54.5% of patients were receiving 10 mg-5 mg (PR oxycodone–PR naloxone) twice a day and 31.3% were receiving 20 mg-10 mg twice a day.

PR oxycodone–PR naloxone was associated with effective analgesia and reduction in symptoms of opioid-induced bowel dysfunction. This combination was associated with minimal adverse events.

• The study had risk of bias due to no appropriate control group.
• The design was observational, with a limited follow-up period.
• Authors did not discuss rescue medication or how rescue medications, medication changes, or other treatments may have affected results.
• A relatively small proportion of patients had cancer. Authors provided no subgroup analysis of different groups of patients.

The fixed combination of PR oxycodone–PR naloxone may be effective in managing chronic pain and cause few problems, such as constipation, which opioids typically cause.