Subcutaneously administered methylnaltrexone (MNTX) (Relistor), a peripherally acting mu-opioid receptor antagonist, relieves opioid-induced constipation (OID) in both chronic, noncancer-related illness and cancer-related illness, a new analysis concludes.
“While these are two very different patient groups, the ability to have something to treat OIC in noncancer patients who stay on opioids for whatever reason helps, because [otherwise] these patients are not doing well,” said lead author Eric Shah, MD, motility director for the Dartmouth program at Dartmouth Hitchcock Health, Lebanon, N.H.
Importantly, peripherally acting mu-opioid receptor antagonists such as MNTX do not affect overall pain control to any significant extent, which is “reassuring,” he said in an interview.
These drugs decrease the constipating effects of opioids without reversing CNS-mediated opioid effects, he explained.
“Methylnaltrexone has already been approved for the treatment of OIC in adults with chronic noncancer pain as well as for OIC in adults with advanced illness who are receiving palliative care, which is often the case in patients with cancer-related pain,” he noted.
Dr. Shah discussed the new analysis during PAINWeek 2020, the American Society of Regional Anesthesia and Pain Medicine 19th Annual Pain Medicine Meeting.
The analysis was based on a review of data collected in two previously reported randomized, placebo-controlled studies (study 302 and 4000), which were used to gain approval.
The new analysis shows that “the drug works up front, and the effect is able to be maintained. I think the studies are clinically relevant in that patients are able to have a bowel movement quickly after you give them an injectable formulation when they are vomiting or otherwise can’t tolerate a pill and they are feeling miserable,” Dr. Shah commented. Many patients with OIC are constipated for reasons other than from opioid use. They often have other side effects from opioids, including bloating, nausea, and vomiting.
“When patients go to the emergency room, it’s not just that they are not able to have a bowel movement; they are often also vomiting, so it’s important to have agents that can be given in a manner that avoids the need for oral medication,” Dr. Shah said. MNTX is the only peripherally acting opioid antagonist available in a subcutaneous formulation.
Moreover, if patients are able to control these symptoms at home with an injectable formulation, they may not need to go to the ED for treatment of their gastrointestinal distress, he added.
Viable product
In a comment, Darren Brenner, MD, associate professor of medicine and surgery, Northwestern University, Chicago, who has worked with this subcutaneous formulation, said it is “definitely a viable product.
“The data presented here were in patients with advanced illness receiving palliative care when other laxatives have failed, and the difference and the potential benefit for MNTX is that it is the only peripherally acting mu-opioid receptor antagonist that is approved for advanced cancer,” he added. The other products that are currently approved, naloxegol (Movantik) and naldemedine (Symproic), are both indicated for chronic, noncancer pain.
The other potential benefit of subcutaneous MNTX is that it can work very rapidly for the patients who respond to it. “One of the things investigators did not mention in these two trials but which has been shown in previous studies is that almost half of patients who respond to this drug respond within the first 30 minutes of receiving the injection,” Dr. Brenner said in an interview.
This can be very beneficial in an emergency setting, because it may avoid having patients admitted to hospital. They can be discharged and sent home with enough drug to use on demand, Dr. Brenner suggested.