Subcutaneously administered methylnaltrexone (MNTX) (Relistor), a peripherally performing µ-opioid receptor antagonist, relieves opioid-induced constipation (OID) in each continual, noncancer-related sickness and cancer-related sickness, a brand new evaluation concludes.

“Whereas these are two very totally different affected person teams, the power to have one thing to deal with OIC in noncancer sufferers who keep on opioids for no matter motive helps, as a result of [otherwise] these sufferers usually are not doing nicely,” mentioned lead creator Eric Shah, MD, motility director for the Dartmouth program, Dartmouth Hitchcock Well being, Lebanon, New Hampshire.

Importantly, peripherally performing µ-opioid receptor antagonists reminiscent of MNTX don’t have an effect on general ache management to any vital extent, which is “reassuring,” he informed Medscape Medical Information.

These medication lower the constipating results of opioids with out reversing central nervous system–mediated opioid results, he defined.

“Methylnaltrexone has already been accredited for the therapy of OIC in adults with continual noncancer ache in addition to for OIC in adults with superior sickness who’re receiving palliative care, which is commonly the case in sufferers with cancer-related ache,” he famous.

Shah was discussing the brand new evaluation throughout PAINWeek 2020, the American Society of Regional Anesthesia and Ache Drugs (ASRA) nineteenth Annual Ache Drugs Assembly.

The evaluation was based mostly on a evaluation of information collected in two beforehand reported randomized, placebo-controlled research (examine 302 and 4000), which had been used to realize approval.

The brand new evaluation reveals that “the drug works up entrance, and the impact is ready to be maintained,” he mentioned. “I believe the research are clinically related in that sufferers are in a position to have a bowel motion rapidly after you give them an injectable formulation when they’re vomiting or in any other case cannot tolerate a tablet and they’re feeling depressing,” Shah commented. Many sufferers with OIC are constipated for causes aside from from opioid use. They typically produce other unwanted effects from opioids, together with bloating, nausea, and vomiting.

“When sufferers go to the emergency room, it isn’t simply that they don’t seem to be in a position to have a bowel motion; they’re typically additionally vomiting, so it is necessary to have brokers that may be given in a way that avoids the necessity for oral remedy,” Shah mentioned. MNTX is the one peripherally performing opioid antagonist obtainable in a subcutaneous formulation.

Furthermore, if sufferers are in a position to management these signs at residence with an injectable formulation, they might not must go to the emergency division for therapy of their gastrointestinal misery, he added.

Viable Product

Approached for remark, Darren Brenner, MD, affiliate professor of medication and surgical procedure, Northwestern College, Chicago, Illinois, who has labored with this subcutaneous formulation, mentioned it’s “positively a viable product.

“The information offered right here had been in sufferers with superior sickness receiving palliative care when different laxatives have failed, and the distinction and the potential profit for MNTX is that it’s the solely peripherally performing µ-opioid receptor antagonist that’s accredited for superior most cancers,” he added. The opposite merchandise which are at present accredited, naloxegol (Movantik) and naldemedine (Symproic), are each indicated for continual, noncancer ache.

The opposite potential good thing about subcutaneous MNTX is that it may possibly work very quickly for the sufferers who reply to it. “One of many issues investigators didn’t point out in these two trials however which has been proven in earlier research is that nearly half of sufferers who reply to this drug reply inside the first half-hour of receiving the injection,” Brenner informed Medscape Medical Information.

This may be very helpful in an emergency setting, as a result of it could keep away from having sufferers admitted to hospital. They are often discharged and despatched residence with sufficient drug to make use of on demand, Brenner prompt.

‘—we ingastroenterology usually are not prescribing them—however whatever the atients keep wholesome at residence and haefects from OICand the SC formulation helps too if sufferers can’t tolerate oral brokers,” he mentioned.

New Evaluation of Knowledge From Research 302 and 4000

Each research had been carried out in adults with superior sickness and OIC whose situations had been refractory to laxative use. Each of the research had been placebo managed.

Research 302 concerned 78 sufferers with most cancers and 56 sufferers with noncancer-related OIC. MNTX was given at a dose of 0.15 mg/kg subcutaneously each different day for two weeks.

Research 4000 included 152 sufferers with most cancers and OIC and 78 sufferers with noncancer-related OIC. On this examine, the dose of MNTX was based mostly on physique weight. Seven or fewer doses of both 8 mg or 12 mg got subcutaneously for two weeks.

The principle endpoints of each research was the proportion of sufferers who achieved a rescue-free laxation (RFL) response inside 4 hours after the primary dose and the proportion of sufferers with an RFL response inside 4 hours for 2 or extra of the primary 4 doses inside 24 hours.

Shah defined that RFL is a significant medical endpoint. Sufferers may obtain a bowel motion with the 2 prespecified time endpoints in each research.

Not all sufferers had been hospitalized for OIC, Shah famous. Entry standards had been strict and included having fewer than three bowel actions throughout the earlier week and no clinically vital laxation (defecation) inside 48 hours of receiving the primary dose of examine drug.

“In each research, a considerably better proportion of sufferers handled with MNTX vs placebo achieved an RFL inside 4 hours after the primary dose amongst each most cancers and noncancer sufferers,” the investigators reported.

Desk 1. Proportion of Sufferers Who Achieved an RFL Response Inside 4 Hours of the First Dose

  Research 302 P worth Research 4000 P worth
Most cancers sufferers: MNTX 51.4%   69.6%  
Most cancers sufferers: placebo 14,6% <.05 15,1% <.001
Noncancer sufferers: MNTX 44%   70.3%  
Noncancer sufferers: placebo 16,7% <.05 22% <.001


Outcomes had been comparatively comparable between most cancers and noncancer sufferers who had been handled for OIC in examine 4000, the investigators word.

Desk 2. Repeat Dosing With Subcutaneous Mntx: RFL Response Inside 4 Hours for Two or Extra of the First 4 Injections, Maintained at 24 Hours

  Research 302 P worth Research 4000 P worth
Most cancers sufferers: MNTX 51.4%   59.5%  
Most cancers sufferers: placebo 7.3% ≤0.0001 6.8% 0
Noncancer sufferers: MNTX 48%   70.3%  
Noncancer sufferers: placebo 10% ≤0.0001 14.6% 0


Each research had been sponsored by Salix Prescribed drugs. Shah has obtained journey charges from Salix Prescribed drugs. Brenner has served as a advisor for Salix Prescribed drugs, AstraZeneca, and Purdue Pharma. AstraZeneca developed naloxegol.

American Society of Regional Anesthesia and Ache Drugs (ASRA) nineteenth Annual Ache Drugs Assembly: Summary 1347. Offered November 21, 2020.