Oxycodone is an opiate analgesic. Naloxone is a competitive opioid-receptor antagonist. At therapeutic oral doses, naloxone exerts a local inhibitory effect on opioid action in the gastrointestinal system. Researchers have studied oxydocone-naloxone, a combination medication, in regard to pain management and in regard to potential to reduce gastrointestinal side effects, such as constipation, in patients who require opioids for pain management.
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Research Evidence Summaries
Nadstawek, J., Leyendecker, P., Hopp, M., Ruckes, C., Wirz, S., Fleischer, W., & Reimer, K. (2008). Patient assessment of a novel therapeutic approach for the treatment of severe, chronic pain. International Journal of Clinical Practice, 62, 1159–1167.doi: 10.1111/j.1742-1241.2008.01820.x
- To assess the analgesic efficacy of prolonged-release (PR) oxycodone in combination with orally administered naloxone PR in patients with severe, chronic pain; to evaluate the efficacy of that combination in improving bowel function
- To evaluate the optimal dose ratio of oxycodone PR to naloxone PR
- To evaluate patients’ and investigators’ treatment preference
Intervention Characteristics/Basic Study Process:
In this three-phase study, patients with inadequate pain control entered the titration period, with stabilization at 40, 60, or 80 mg oxycodone PR/day. Those on stable oxycodone dosing who used laxatives to have three bowel movements per week were entered in the maintenance phase after a seven-day run-in period. After patients were stabilized, they were randomized into three naloxone treatment groups or a placebo group. Oxycodone was given open label; naloxone was given in double-blind fashion. After a patient was in the maintenance phase, no titration of oxycodone PR doses was allowed. Those using laxatives were advised to stop unless no bowel movement had occurred for three days. Patients were studied for four weeks, then assessed in a two-week follow-up phase. In the follow-up phase, no one received naloxone PR.
- The intent-to-treat (ITT) group, defined as those who were randomized and received at least one dose of naloxone or placebo and had at least one efficacy assessment, comprised 196 patients; 166 patients completed the study.
- Patients were older than 18 years.
- The sample was 62.9% female and 37.1% male.
- Specific cancer type was not reported.
- Twenty-eight centers in Germany, May 2002 to April 2003
Prospective randomized double-blind, parallel-group, phase II trial
- Rating scale (1 = very good, 7 = very poor), to measure efficacy and tolerability, used independently by investigators and patients
- Preference, in regard to tolerability and efficacy, for maintenance phase or titration–run-in phase (1 = titration–run-in, 2 = maintenance, 3 = no preference)
- The efficacy of the 2:1 dose ratio of oxycodone PR to naloxone PR was ranked as good or very good by 70.4% of patients and investigators.
- The tolerability of the 2:1 dose ratio was ranked as good or very good by 81.5% of patients and investigators.
- The majority of patients in the treatment arm preferred the maintenance phase, in which they received both medications.
- Naloxone PR had no impact on the analgesic efficacy of oxycodone PR; naloxone PR improved bowel function and reduced laxative intake.
Concurrent administration of oxycodone PR and naloxone PR is effective for the treatment of patients with severe chronic pain, cancer-related or not. Patients tolerated naloxone PR well; naloxone created no additional untoward effects.
- Exclusion of patients with severe cardiovascular or pulmonary issues limits the applicability of findings to patients with advanced cancers and those taking more than five medications per week to control breakthrough pain.
- Oxycodone PR dosing was limited to 40–80 mg/day.
This study's results relate to pain control and bowel function of patients with cancer. Additional research, to investigate widening application of the findings, is warranted.
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.doi: 10.1185/03007991003787318
To evaluate the safety and efficacy of combined prolonged-release (PR) oxycodone and PR naloxone for treatment of cancer-related pain in daily practice
Intervention Characteristics/Basic Study Process:
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.
- Germany (6,496 sites)
- 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.