Clinical Overview and Considerations for the Management of Opioid-induced Constipation in Patients With Chronic Noncancer Pain

Abstract

Objectives:Opioid analgesics may be associated with chronic adverse effects, such as opioid-induced constipation (OIC). Available and emerging prescription medications for OIC in patients with chronic noncancer pain are described, including concerns and challenges associated with OIC management.Methods:Narrative review.Results:OIC is characterized by a change in bowel habits and defecation patterns that occurs when initiating opioid therapy and is associated with reduced bowel frequency, straining, sensation of incomplete evacuation, and/or patient distress related to bowel habits. Prescription medications are indicated when OIC persists despite conservative approaches (eg, increased fiber and fluid intake, exercise, over-the-counter laxatives and stool softeners). Phase 3 studies have demonstrated the efficacy of peripherally acting µ-opioid receptor antagonists (PAMORA; methylnaltrexone, naloxegol, naldemedine), and a chloride channel activator (lubiprostone) for improving OIC in patients with chronic noncancer pain. Although head-to-head studies are lacking, a meta-analysis demonstrated that μ-opioid receptor antagonists were more effective than placebo for the treatment of OIC. The most common adverse effects associated with prescription medications for OIC are gastrointestinal related (eg, nausea, diarrhea, abdominal pain, or distention), with most being mild or moderate in severity. Therapy currently in development for OIC includes the PAMORA axelopran.Discussion:Health care providers should be aware of this complication in patients receiving opioids and should monitor and address constipation-related symptoms to optimize pain management and improve patient quality of life.

What to Do and What Not to Do in the Management of Opioid-Induced Constipation: A Choosing Wisely Report

“…PAMORAs have not demonstrated significant efficacy for OIC prevention, but physicians should be aware of their excellent utility and tolerability for OIC management [41]. Physicians should however pay careful attention to the use of PAMORAs in patients with abdominal cancer or complete or partial bowel obstruction due to the risk of precipitating cramps or colicky pain [32,42].…”

<p>The Use of Peripheral μ-Opioid Receptor Antagonists (PAMORA) in the Management of Opioid-Induced Constipation: An Update on Their Efficacy and Safety</p>

“…69 It is not clear if PAMORAs have different effects depending on the type of opioid the patient is taking, but there is some limited evidence that methadone may inhibit the mechanism of action of lubiprostone 70 and there is a higher rate of adverse events when methadone patients use naloxegol. 69 Known or suspected gastrointestinal obstruction or the risk of recurrence for a past obstruction contraindicate the use of PAMORAs because of the risk for gastrointestinal perforation. 69 Opioid withdrawal symptoms are of concern when using PAMORAs as they are opioid antagonists being used in patients who are likely opioid dependent.…”

“…69 Known or suspected gastrointestinal obstruction or the risk of recurrence for a past obstruction contraindicate the use of PAMORAs because of the risk for gastrointestinal perforation. 69 Opioid withdrawal symptoms are of concern when using PAMORAs as they are opioid antagonists being used in patients who are likely opioid dependent. A few such cases have been observed in various studies, but they are rare.…”

Blood–brain barrier: mechanisms governing permeability and interaction with peripherally acting μ-opioid receptor antagonists

“… 72 82–84 PAMORAs are able to reduce the symptoms of OIC while maintaining the efficacy of opioid agonists in the CNS. 73 76 85 86 Three PAMORAs have been developed to treat OIC: methylnaltrexone (Relistor), 87 naloxegol (Movantik), 88 and naldemedine (Symproic). 89 A fourth PAMORA, alvimopan (Entereg), is indicated to accelerate the time to upper and lower gastrointestinal recovery following surgeries that include partial bowel resection with primary anastomosis.…”

“…However, there are several publications that have reviewed the efficacy and safety of this class. 73 91–94 …”