Plain language summary
Mu-opioid antagonists for bowel dysfunction due to opioids in people with cancer and people receiving palliative care
Opioids (morphine-like drugs) are used to treat severe pain. Unfortunately, they cause side effects. Opioid-induced bowel dysfunction (OIBD) is a term used to describe constipation, incomplete evacuation of the bowels, bloating, and increased reflux (flowing back) of stomach contents. OIBD may be so severe that a person chooses to limit opioid treatment to improve bowel function. OIBD is common in people with cancer and people receiving palliative care (care given to people with a terminal illness when a cure is no longer possible). Laxatives are often the first-choice treatment for OIBD. They may not always work. Mu-opioid antagonists (MOA) are specific medicines for OIBD. Clinical guidelines may recommend them when laxatives fail.
The aim of this updated review was to determine what we know about the effectiveness and safety of MOA for the management of OIBD in people with cancer and people receiving palliative care and for whom laxatives have failed. A possible side effect of an MOA is reduced pain relief from opioids; therefore, we looked at its impact on pain relief. We only included randomised controlled trials (RCTs), which are well-designed clinical trials that provide the most reliable evidence. RCTs needed to evaluate an MOA, such as the medicines naldemedine, methylnaltrexone, and naloxone. The trial comparison groups could be a placebo (a substance with no known active effect), usual care, or another treatment such as a different type of MOA.
Our search to August 2017 found eight trials involving 1022 adults. The MOAs evaluated in people with cancer were oral naldemedine and naloxone taken in combination with an opioid treatment (for pain). Methylnaltrexone given by injection was evaluated in palliative care where most participants had advanced cancer.
The results were naldemedine or methylnaltrexone compared with placebo. For naloxone, they were either in comparison with a placebo or with opioid treatment only.
We rated the quality of the evidence from studies as very low to moderate. Very low means that we are very uncertain about the results. High means that we are very confident in the results. There were problems with the design of studies, including under-reporting of trial methods.
Bowel movements within 24 hours and up to two weeks
There was moderate-quality evidence that naldemedine increased bowel movements up to two weeks. Trials did not measure the effects of naloxone on bowel movements at two weeks. Methylnaltrexone increased bowel movements or laxations (softer stools) within 24 hours and up to two weeks (moderate-quality evidence).
There was moderate-quality evidence that naldemedine did not change pain relief. Trials did not measure pain intensity with naldemedine. There was very low-quality evidence that naloxone taken on its own did not change pain relief. There was moderate-quality evidence that naloxone taken with an opioid treatment did not change pain relief. There was moderate- to low-quality evidence that methylnaltrexone did not change pain relief.
Risk of serious side effects (hospitalisation, life-threatening, or fatal) and other side effects
There was low-quality evidence that naldemedine and naloxone in combination with an opioid treatment did not increase the risk of serious side effects. For naldemedine, there were five serious side effects in the trial, although none were described as relating to the study drug. Methylnaltrexone probably did not increase the risk of serious side effects (moderate-quality evidence).
There was moderate-quality evidence that naldemedine increased the risk of side effects. There was moderate-quality evidence that naloxone taken with oxycodone (an opioid painkiller) did not increase the risk of side effects. There was low-quality evidence that methylnaltrexone did not increase the overall risk of a side effect. Methylnaltrexone increased the risk of abdominal pain and flatulence.
There was moderate-quality evidence to suggest that naldemedine improved bowel function over two weeks in adults with cancer and OIBD but increased the risk of side effects; and that methylnaltrexone improved bowel function in people receiving palliative care and low-quality evidence that methylnaltrexone did not increase side effects. The results of this review need to be interpreted with caution as they were not obtained from high-quality evidence. There were no studies in children.