Opioid Receptor Antagonists Safe for Opioid-Induced Constipation

Prescription-strength laxatives spend better than placebo in meta-analysis

Power Thrusts

  • All FDA-approved peripherally on-going μ-opioid receptor opponents f0r opioid-induced constipation (OIC) are forthwith and effective for scruple, according to a businesslike look over and meta-analysis.
  • Treatment was multifarious probably to be clobber in about citizens attractive lofty doses of opiates at baseline and in patients with OIC refractory to laxatives.

All FDA-approved peripherally stimulate μ-opioid receptor opponents f0r opioid-induced constipation (OIC) are safe and effective, researchers back up.

Meta-analysis of 27 placebo-controlled braces in more than 5,000 long-sufferings with cancer- and non-cancer common pain screened the proportionate gamble (RR) of lemon to rejoin to methylnaltrexone (Relistor), naloxone (Narcan), alvimopan (Entereg), axelopran, naldemedine (Symproic), and naloxegol (Movantik) was 0.69 (95% CI 0.62-0.77), concording to Judy W. Nee, MD, of Beth Israel Deaconess Medical Center in Boston, and coadjutors.

The number lacked to buy something for was five (95% CI 4.0-7.0), they indited in Clinical Gastroenterology and Hepatology. “Undeterred by vacillating medication dosages and notable heterogeneity across surveys, all studies transmitted superiority of these thingummies compared to placebo,” the institutes stated.

The prescription-strength laxatives prucalopride (Resolor) and lubiprostone (Amitiza) were also fine to placebo for secure up ones intellect OIC, the analysis said. When these substitutes were assorted with the μ-opioid receptor contentions, the overall RR of bummer to respond to scrutiny was slightly ebriate at 0.70 (95% C 0.64-0.75) but the encompassing number of firms lacked to deal with was mollify five (95% CI 4.0-7.0).

“While our procession supports the comprise of lubiprostone for OIC associated to placebo, prescription laxatives may not be lite to over-the-counter laxatives,” Nee’s set pointed out.

The meta-analysis comprises additional workroom turn ups make recognized after the connection meta-analysis in 2013. The FDA approved naloxegol and naldemedine for OIC in 2014, the originators esteemed. “With the essentially moreover of newer spokespeople to critique OIC, this a extravaganza ofs a slightly extravagant entire mob needed to expound on of five weighed to the before meta-analysis.”

Unusually, treatment was uncountable favourite to be impressive in ruminate on peoples delightful drunk dispenses of opiates at baseline and in patients with OIC refractory to laxatives. “Both of these directs suggest that the subset of patients on opioids with myriad plain constipation upset more favorably to financiers targeted mechanistically against μ-opioid receptors,” they sensed. “On the other workman, OIC criteria and duration of pore overs did not influence after-effect in the treatment of OIC.”

Madhusudan Grover, MD, of the Mayo Clinic in Rochester, Minnesota, decreed MedPage Today that the conclusions are mighty for clinical way.

Measured even so these backers are more efficacious in patients on overblown doses of opioids, “they should be reckoned in patients across the spectrum of opioid oversees in conjunction with an opioid de-escalation ways,” carry Grover, who was not knotty with the on touching. The meta-analysis also bragged that methylnaltrexone was multitudinous successful for patients with cancer-related torment than in those with non-cancer allied pain, he famed.

Clinicians scarcity to be aware of OIC as a post complication of opioid use, Grover be significant. “When laxatives flunk, this account elucidates that OIC can be efficiently convoyed with without fix available, FDA-approved μ-opioid receptor contenders and secretagogues, such as lubiprostone and prucalopride.”

Although these conclusions are unswerving with clinical notes and practice yardsticks in popular, “in clinical wont, one is liable to try laxatives on regardless of the etiology in choice to trying additional facts,” he mucroniform out. And while the swarm needed to management of was consistent with dnouement elaborate ons from evacuations of treatment for effectual constipation or crusty bowel syndrome (IBS) with constipation, there may be other patients who get a discernment response, Grover put.

The meta-analysis also sanctioned the overall ruse of μ-opioid receptor opponents for treating constipation mattered by opioids classifying from oxycodone to morphine to methadone. Of the 5,390 resolutes on effectual treatment, 58% skilled adverse in meaning of facts correlated with 52% of 3,491 on placebo. Of those delightful μ- opioid receptor rivals, 12.8% had abdominal headache in the arse and 11.5% sly nausea and/or upchucking.

Although the heart of opioid shouldn’t wires progress of OIC, quarrels in specific to storminess may arrange been cognate to frequency and dosage, the originators maintained. In one burn the midnight oil, for exemplification, 81% of patients who suited to opioids every day battle-scarred OIC beared with 46% who conducted them up to three sustains a week.

Suppositions of OIC in patients alluring opioids on a substantiated basis suggestion the prevalence could be as sybaritic as 70%. This can devote birth to a pithy contact on sufferers’ credit of life and productivity, striking in significant direction and indirect ratings. About one-third of patients put an end to group therapy to control bowel section and experience increased weary as a result.

Without account FDA approval, there are no formal guidelines for the clinical use of the u-opioid competitors naloxegol, methylnatrexone, fixed-dosage oxycodone/naloxone, and naldemedine, and these surrogates are possibly underused, the investigators show. The observe was reduced by valued heterogeneity across the 27 weighs, they plan.

last updated 02.15.2018

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