Methylnaltrexone rapidly relieves Opioid-Induced Constipation, finds study
Subcutaneous administration of Methylnaltrexone, in both chronic, noncancer-related illness and cancer-related illness, relieves Opioid Induced Constipation suggests a study which was presented in 19th Annual Pain Medicine Meeting at American Society of Regional Anesthesia and Pain Medicine.
Opioid medications have long been a cornerstone of cancer pain treatment, despite the risks of adverse effects, addiction and development of tolerance associated with chronic use. Constipation is one of the most common side effects of opioid treatment, with an incidence of up to 60% in patients treated for cancer-related pain. Surveys have shown that approximately one quarter to one-half of patients has skipped, decreased or discontinued opioid use because of constipation, in essence accepting one discomfort in hopes of relieving another. Methylnaltrexone a selective, peripherally acting μ-opioid receptor antagonist improves GI motility and transit time without affecting μ-opioid receptor-mediated analgesia. Methylnaltrexone (MNTX) is the only FDA approved formulation for OIC for patients with cancer.
Researchers conducted a post hoc analysis comprising two Phase III, multicenter, double-blind, randomized studies of advanced-illness patients who received methylnaltrexone subcutaneous injection or placebo (study 302 [NCT00402038] and study 4000 [NCT00672477]).
The study 302 involved patients from 27 sites (26 US; 1 Canada).A total of 78 cancer patients (MNTX n=37; placebo n=41) and 56 non cancer patients (MNTX n=26; placebo n=30) were randomized to receive MNTX subcutaneous (SC) 0.15 mg/kg or placebo every other day for 2 weeks.
Study 4000 involves patients from 48 US and international sites.About 152 cancer patients (MNTX n=79; placebo n=73) and 78 noncancer patients (MNTX n=37; placebo n=41) were randomized to receive MNTX SC based on body weight (8 or 12 mg) or placebo for less than or equal 7 doses for 14 days.
The main endpoints of both studies were the proportion of patients who achieved a rescue-free laxation (RFL) response within 4 hours after the first dose and the proportion of patients with an RFL response within 4 hours for two or more of the first four doses within 24 hours.
Key findings of the study were:
- ♦Upon analysis, the researchers observed in both studies, a significantly greater proportion of patients treated with MNTX versus placebo achieved an RFL (rescue-free laxation) within 4 hours after the first dose among cancer and noncancer patients.
- ♦They noted repeat administration of MNTX SC also maintained bowel symptom response within 4 hours in both cohorts.
- ♦However, they didn't observe any significant changes in pain scores between treatment groups.
- ♦The most common adverse events observed were abdominal pain, flatulence, and nausea.
Proportion of Patients with an RFL Response Within 4 Hours of the First Dose in %
Study 302 | Study 4000 | |
Cancer patients: MNTX | 51.4% | 69.6% |
Cancer patients: placebo | 14.6% | 15.1% |
Noncancer patients: MNTX | 44% | 70.3% |
Noncancer patients: placebo | 16.7% | 22% |
Proportion of patients with an RFL Response Within 4 Hours for Two or More of the First Four Injections (Repeat dosing)
Study 302 | Study 4000 | |
Cancer patients: MNTX | 51.4% | 59.5% |
Cancer patients: placebo | 7.3% | 6.8% |
Noncancer patients: MNTX | 48% | 70.3% |
Noncancer patients: placebo | 10% | 14.6% |
The authors concluded, "In 2 individual studies, MNTX use effectively reduced OIC within 4 hours of the first dose and maintained bowel symptom response with repeat dosing in cancer and non-cancer patients without affecting central opioid receptor-mediated analgesia".
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