Abstract | BACKGROUND AND OBJECTIVES: In patients with chronic noncancer pain, subcutaneous methylnaltrexone for opioid-induced constipation (OIC) was examined in a randomized controlled trial (RCT) followed by an open-label extension (OLE). This study examined the reproducibility of RCT findings by analyzing data from placebo-treated patients who crossed over to methylnaltrexone. METHODS: Adults with less than 3 weekly rescue-free bowel movements (RFBMs), taking 50 mg or more of an oral morphine equivalent per day, were randomized to receive methylnaltrexone 12 mg or placebo for 4 weeks, followed by open-label methylnaltrexone 12 mg as needed for 8 weeks. RESULTS: A total of 134 placebo-treated patients (median morphine equivalent dose, 150 mg/d; mean of 1.1 RFBM per week) crossed over to methylnaltrexone in OLE. During the RCT, 9.7% of placebo-treated patients experienced an RFBM within 4 hours of first dose and 9.0% of all placebo injections resulted in an RFBM within 4 hours compared with 45.9% and 34.5%, respectively, with methylnaltrexone treatment in the OLE. When expressed as percentage of patients experiencing 3 or more RFBMs per week and a 1-RFBM increase over baseline, weekly values ranged from 35% to 40% during placebo treatment; at week 5 of OLE methylnaltrexone, this percentage increased to more than 70% and remained relatively stable throughout the OLE. The most common adverse events during methylnaltrexone treatment were abdominal pain (9.7% vs 1.5% for placebo) and nausea (5.2% vs 6.7%). CONCLUSIONS: Findings during placebo treatment further establish the profile of OIC and support that little or no gastrointestinal tolerance develops across time. Findings under open-label conditions established the reproducibility and durability of methylnaltrexone for OIC.
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Authors | Eugene R Viscusi, Andrew C Barrett, Craig Paterson, William P Forbes |
Journal | Regional anesthesia and pain medicine
(Reg Anesth Pain Med)
2016 Jan-Feb
Vol. 41
Issue 1
Pg. 93-8
ISSN: 1532-8651 [Electronic] England |
PMID | 26650429
(Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics, Opioid
- Narcotic Antagonists
- Quaternary Ammonium Compounds
- methylnaltrexone
- Naltrexone
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Analgesics, Opioid
(adverse effects)
- Chronic Pain
(diagnosis, drug therapy)
- Constipation
(chemically induced, diagnosis, drug therapy)
- Cross-Over Studies
- Double-Blind Method
- Female
- Humans
- Male
- Middle Aged
- Naltrexone
(analogs & derivatives, therapeutic use)
- Narcotic Antagonists
(therapeutic use)
- Quaternary Ammonium Compounds
(therapeutic use)
- Treatment Outcome
- Young Adult
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