Bull, J., Wellman, C.V., Israel, R., Barrett, A.C., Paterson, C., & Forbes, W.P. (2015). Fixed-dose subcutaneous methylnaltrexone in patients with advanced illness and opioid-induced constipation: Results of a randomized, placebo-controlled study and open-label extension. Journal of Palliative Medicine, 18, 593–600. 

DOI Link

Study Purpose

To determine safety and efficacy of fixed doses of methylnaltrexone (MNTX) in patients with advanced disease

Intervention Characteristics/Basic Study Process

After participation in a two-week placebo randomized controlled trial (RCT), patients were eligible to enroll in a 10-week open-label extension study to evaluate the use of MNTX at a fixed dose based on weight using as-needed dosing. Patients were dosed at 8 mg SC for weight of 38 kg to less than 62 kg or, if 62 kg or greater, at a dose of 12 mg. Doses were administered as needed but not more often than daily. Rescue doses of other bowel medications were permitted if the MNTX was not effective. Patients were taking stable laxative regimens and a stable dose of opioids.

Sample Characteristics

  • N = 230  
  • MEAN AGE = 65.9 years
  • MALES: 50.9%-51.7%, FEMALES: 48.3%-49.1%
  • KEY DISEASE CHARACTERISTICS: Advanced illness, with 57%-66% having a cancer diagnosis

Setting

  • SITE: Multi-site    
  • SETTING TYPE: Multiple settings  
  • LOCATION: United States

Phase of Care and Clinical Applications

  • PHASE OF CARE: End-of-life care
  • APPLICATIONS: Palliative care 

Study Design

  • Open-label extension study following a prior clinical trial using MNTX for the management of opioid-induced constipation

Measurement Instruments/Methods

  • Diary of bowel function
  • Clinic visits

Results

MNTX was effective in the management of opioid-induced constipation in both the RCT and the open-label extension study. The results were based on rescue free bowel movements after doses of MNTX. For the MNTX arm in the RCT component, 62.9% of patients had bowel function compared with 9.6% of the placebo control group (p < 0.0001). Weight did not have an effect on outcome. Secondary end points were all in favor of MNTX, including time to bowel function after first dose. The most common side effects were abdominal pain and nausea.

Conclusions

A fixed dose of MNTX is safe and effective in the management of opioid-induced constipation in patients with advanced disease.

Limitations

  • Risk of bias (no blinding)
  • Patients under 38 kg were not eligible
  • Short study duration

Nursing Implications

This study adds support to the data that MNTX is safe and effective for opioid-induced constipation.