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The Influence of Age on Central Effects of Methylnaltrexone in Patients with Opioid-Induced Constipation
Solomon S Liao1, Neal E Slatkin2,3, Nancy Stambler4
1Palliative Care Service Hospitalist Program, University of California Irvine Medical Center, 101 South City Drive, Bldg 26, ZC4076H, Orange, CA, 92868, USA. ssliao@hs.uci.edu.
Background:
Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist approved for the treatment of opioid-induced constipation (OIC), has restricted diffusion across the blood-brain barrier (BBB) and has not been demonstrated to impact opioid-induced central analgesia. Age-related changes in BBB permeability may compromise methylnaltrexone's restricted diffusion and alter opioid-induced central analgesic effects.
Objective:
This analysis evaluated whether opioid analgesia is compromised in older adults receiving methylnaltrexone for OIC.
Methods:
The analysis included adults diagnosed with OIC who received opioids for pain management and who had a terminal illness or chronic nonmalignant pain. Data were pooled from four randomized, double-blind trials and stratified by age (< 65 years and ≥ 65 years). Endpoints included pain intensity scores, symptoms of opioid withdrawal, treatment-related adverse events (TRAEs), and rescue-free laxation (RFL) within 4 h of treatment.
Results:
Overall, 1323 patients were < 65 years of age (n = 908, methylnaltrexone; n = 415, placebo) and 304 patients were ≥ 65 years of age (n = 171, methylnaltrexone; n = 133, placebo). Nonsignificant pain intensity score reductions were observed in all groups. In the older cohort, measures of opioid withdrawal did not show statistical differences from baseline in either the methylnaltrexone or placebo groups. The most frequently reported TRAEs were abdominal pain, flatulence, and nausea. Relative to the first dose, gastrointestinal TRAEs potentially related to opioid withdrawal declined with the second dose and were comparable with placebo, regardless of age. RFL response within 4 h of methylnaltrexone treatment increased significantly in both age cohorts relative to placebo.
Conclusions:
Methylnaltrexone use did not adversely affect pain control, opioid withdrawal effects, or AEs while providing effective RFL, regardless of age. These results suggest that age does not appear to influence the safety and efficacy of methylnaltrexone for OIC. Further research is needed to assess the impact of other factors that alter BBB permeability, such as dementia, stroke, or drug interactions, on the safety and efficacy of methylnaltrexone.
Clinical Trial Registration Numbers:
Study 302, NCT00402038; study 3200K1-4000, NCT00672477; study 3200K1-3356, NCT00529087; study 3201, NCT01186770.
Insights
Methylnaltrexone effectively treats opioid-induced constipation (OIC) without compromising pain relief or causing significant adverse effects in older adults. This study confirms methylnaltrexone
Area of Science:
- Pharmacology and Geriatric Medicine
- Investigating the safety and efficacy of peripherally acting µ-opioid receptor antagonists in elderly populations.
Background:
- Methylnaltrexone is approved for opioid-induced constipation (OIC) and has limited blood-brain barrier (BBB) penetration.
- Age-related changes in BBB permeability may affect methylnaltrexone's efficacy and opioid analgesia.
- Concerns exist regarding methylnaltrexone's impact on central analgesic effects in older adults.
Purpose of the Study:
- To evaluate if methylnaltrexone compromises opioid-induced analgesia in elderly patients with OIC.
- To assess the safety and efficacy of methylnaltrexone across different age groups.
Main Methods:
- Pooled data from four randomized, double-blind trials involving patients with OIC.
- Patients received opioids for pain management and were stratified by age (<65 and ≥65 years).
- Evaluated endpoints included pain intensity, opioid withdrawal symptoms, adverse events, and rescue-free laxation (RFL).
Main Results:
- Methylnaltrexone did not significantly alter pain intensity scores in any age group.
- Older adults (≥65 years) showed no significant opioid withdrawal symptoms with methylnaltrexone or placebo.
- Methylnaltrexone demonstrated effective RFL within 4 hours, comparable to placebo, across both age cohorts.
Conclusions:
- Methylnaltrexone is safe and effective for OIC in older adults, without negatively impacting pain control or causing significant adverse events.
- Age does not appear to influence the safety and efficacy of methylnaltrexone for OIC.
- Further research is recommended to explore the influence of factors affecting BBB permeability on methylnaltrexone's effects.
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