Lipman, A.G., Karver, S., Cooney, G.A., Stambler, N., & Israel, R.J. (2011). Methylnaltrexone for opioid-induced constipation in patients with advanced illness: A 3-month open-label treatment extension study. Journal of Pain and Palliative Care Pharmacotherapy, 25, 136-145.

To provide access to methylnaltrexone for patients who participated in a prior study of the agent, and to continue to evaluate the safety and efficacy of methylnaltrexone in patients with opioid-induced constipation.

This open-label drug extension study recruited participants from both the control and active treatment groups of a prior methylnaltrexone study. All patients were at the end of life, were not pregnant, and were using birth control. Patient received methylnaltrexone 0.15 mg/kg subcutaneously as needed once per day. The dose was increased to 0.3 mg/kg if the agent was not effective in four hours.  The dose was reduced to 0.075 mg/kg if the patient had adverse events. 

• The study reported on a sample of 89 participants (39% male and 61% female).
• Mean age was older than 65 years (range 66.9–68.9).
• Most participants (55.9%) were diagnosed with cancer.

• Multi-site
• Inpatient and outpatient
• United States
   

• Patients were undergoing the end-of-life phase of care.
• The study has clinical applicability for end-of-life and palliative care.

This was a nonrandomized, single-arm, drug continuation study.

• Rescue-free laxation time period    
• Efficacy endpoints identified by the research team
• Modified Himmelsbach Scale
• Global Clinical Impression of Change
   

All patients (control group and active treatment group, as defined in the prior study) received a minimum of one drug dose. Patient laxation effect was similar between the active treatment (45.3%) and control (48.3%) groups. Most patients had an effect in less than one hour. Side effects included abdominal pain, nausea, and vomiting. Serious adverse events considered drug related were muscle spasms, abdominal pain, and pain exacerbation. The effect on patient pain levels was minimal. Opioid withdrawal symptoms ranged from none to mild.  

Patients obtained benefit from methylnaltrexone for up to three months, and the agent was well tolerated.

•  The sample size was small (less than 100).
•  The study had no true control group, as control patients also received methylnaltrexone in this extension study.
   

Patients at the end of life who have an ongoing need for methylnaltrexone may continue to receive an effect from the drug for up to three months when it is used as needed.