Koopmans, G., Simpson, K., De Andres, J., Lux, E. A., Wagemans, M., & Van Megen, Y. (2014). Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives. Current Medical Research and Opinion, 30, 2389–2396. 

DOI Link

Study Purpose

To determine the effect of a combination of oxycodone and naloxone prolonged release tablets (OXN PR) on opioid-induced constipation and pain in patients with moderate to severe cancer- or noncancer-related pain

Intervention Characteristics/Basic Study Process

Patients had received OXN PR in prior double-blinded, multicenter, randomized studies. In one previous study (also a pooled analysis of two Phase III studies), patients with noncancer-related pain received 12 weeks of OXN PR or oxycodone prolonged release (Oxy PR) at the dose equivalent of 20–50 mg per day or 60–120 mg per day. After a 7–28-day period, patients were titrated to an effective analgesic dose of Oxy PR. In a previous Phase II study, patients with moderate to severe cancer-related pain were screened for 3–10 days and then switched to OXN PR or Oxy PR for four weeks (20–120 mg per day). In all prior studies, bisacodyl at 10 mg per day could be taken orally as a rescue laxative 72 hours after a previous bowel movement or when the patient experienced discomfort for a maximum of five doses in seven consecutive days. In all previous studies, data were collected at screening, at the start of the intervention period, and at the end of the intervention period. Laxative use was documented throughout the intervention period in all studies.

Sample Characteristics

  • N = 75  
  • MEDIAN AGE = 62 years (range = 40–80 years)
  • MALES: Unknown, FEMALES: Unknown
  • OTHER KEY SAMPLE CHARACTERISTICS: 53.3% of patients had cancer-related pain.

Setting

  • SITE: Multi-site    
  • SETTING TYPE: Not specified  
  • LOCATION: Netherlands

Phase of Care and Clinical Applications

  • PHASE OF CARE: Multiple phases of care
  • APPLICATIONS: Elder care 

Study Design

Pooled analysis

Measurement Instruments/Methods

  • Bowel Function Index (BFI)
  • Brief Pain Inventory Short Form (BPI-SF)
  • Documentation of adverse effects 

Results

The overall BFI score at screening was 62.5 (SD = 18.7) in patients with and without cancer-related pain, and it was 66.4 in patients with cancer-related pain. Scores on the BFI scale decreased at the end of the intervention period (in the second study, patients with cancer) showing a decrease of 19 (SD = 28.9) after 24.7 days of treatment (p = .0002). The number of patients who had a BFI score within the normal range increased in patients with cancer-related pain from 5.1% prior to randomization to 27.8% on day 8 and 36.4% on day 15. Patients in all studies reported using at least two types of laxatives prior to study enrollment, and 64% of patients in both groups used the study laxative during the intervention period. Throughout the intervention period, 36% of patients in both groups (cancer- and noncancer-related pain) stopped using laxatives (p < .001). Laxative use was more frequent in patients with cancer-related pain (82.5%, median = 6 [range = 1–20] tablets) compared to noncancer-related pain (42.9%, median = 10 [range = 1–36] tablets). The mean daily dose of study laxative in patients with cancer-related pain was 2.1 mg.
 
No difference was seen in pain scores. A nonsignificant trend was seen in improving pain scores in patients with cancer-related pain (mean change = -0.4, p = .311). A significant decrease was seen in the median dose of rescue medication (OXY IR) in patients with cancer-related pain from days 1–7 (3.93 mg) to days 29–35 (1.25 mg, p = .0018). 27.5% of patients with cancer-related pain reported adverse events, and severe adverse events were more common in patients with cancer-related pain versus noncancer-related pain (25% versus 2.9%). The most common adverse events were constipation (9.3%), nausea (9.3%), and vomiting (8%).

Conclusions

The high BFI score at the time of screening indicated that both groups of patients experienced constipation and that patients with cancer-related pain experienced more symptoms. OXN PR clinically and statistically improved constipation in patients with chronic cancer- and noncancer-related pain. Laxative use decreased during the intervention period, and more patients fell within the range of normal bowel habits as the intervention progressed. Pain scores did not change during the intervention period although there was a nonsignificant trend of pain improvement in patients with cancer-related pain.

Limitations

  • Small sample (< 100)
  • Findings not generalizable
  • Other limitations/explanation: The studies that were used differed in length of treatment (4 versus 12 weeks). Demographic information was limited although the authors stated that there was no difference between the groups. Only 40 patients with cancer-related pain were included in the analysis. It appears as though some of the patients with cancer-related pain were receiving end-of-life care, but this is not entirely clear. Limited outcomes were reported for pain.

Nursing Implications

OXN PR may be a viable pharmacologic intervention to achieve pain control in patients with cancer-related pain while minimizing the symptoms of opioid-induced constipation. OXN PR reduced laxative use and increased the number of patients who reported normal bowel function. OXN PR did not change pain scores.