In the Journals

AGA Provides Guidance on Managing GI Side Effects of Opioids

Michael Camilleri, MD
Michael Camilleri

A new American Gastroenterological Association Clinical Practice Update provides guidance on managing the gastrointestinal symptoms and side effects of opioids.

Michael Camilleri, MD, of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., and co-authors emphasized that considering the widespread use of opioids in the U.S., gastroenterologists should understand the beneficial or adverse effects these medications can have on the GI tract, and how to prevent and effectively treat them.

“Opioids are frequently encountered in clinical practice either as cause of patients’ symptoms or as the treatment for symptoms,” Camilleri told Healio Gastroenterology and Liver Disease. “Opioids have pharmacological effects on the entire gastrointestinal tract from the lower esophageal sphincter to the anorectum, and including the gall bladder and biliary tract.”

As opioid receptors are densely populated in the GI tract, patients taking opioids commonly experience conditions like opioid-induced constipation (OIC), esophageal dysmotility, delayed gastric emptying, and a unique condition called narcotic bowel syndrome, the authors wrote.

“Increasingly, the opioid epidemic is manifested in patients seen in gastroenterology practice as OIC and narcotic bowel syndrome,” Camilleri said. “Clinical guidelines on treatment of these conditions are available and help optimize patient management.”

Opioid-induced constipation

OIC is caused by mu opioids increasing fluid absorption and inhibiting colonic motility, and is generally defined as a change in bowel habits and defecation patterns after a patient starts taking opioids, Camilleri and colleagues wrote. The condition is characterized as having fewer than three weekly spontaneous bowel movements, straining, sensing incomplete evacuation and harder stool consistency. The authors noted that even low doses of opioids can cause OIC, and it can occur any time after a patient begins taking opioids.

Regarding prevention and treatment strategies for OIC, they recommended that laxatives should be a first-line treatment, or even be given prophylactically, although this is rarely done. If laxatives provide insufficient clinical benefit, they advised that prescription OIC treatments should be considered. These include Amitiza (lubiprostone, Sucampo/Takeda), Relistor (methylnaltrexone, Salix Pharmaceuticals), and Movantik (naloxegol, AstraZeneca). The FDA also recently approved Symproic (naldemedine, Shionogi/Purdue) for OIC, but this was not included in the article as it was not available for prescription at the time the article was submitted for publication.

Camilleri and colleagues also mentioned that naloxone, the IV drug used to treat opioid overdoses, has been shown to improve OIC symptoms when taken orally, and suggested that using Nucynta (tapentadol, Ortho-McNeil-Janssen Pharmaceuticals) or Targiniq ER (Purdue Pharma), a fixed-dose combination of oxycodone and naloxone, as alternatives to other opioids may be effective, as they have fewer GI adverse effects.

Narcotic bowel syndrome

The authors also described narcotic bowel syndrome, which involves persistent moderate-to-severe abdominal pain occurring daily for more than 3 months in patients taking more than 100 mg of morphine equivalent per day. In this syndrome, the abdominal pain does not respond to narcotics, and may even intensify in response to increasing doses.

While the underlying mechanisms of narcotic bowel syndrome remain unclear, it differs from general causes of pain in those taking opiates “because it is a disease of nociception independent of the opioid effects on gut motility and secretion,” Camilleri and colleagues wrote.

Unfortunately, treatment is difficult, and requires detoxification and substitution of opioids, which is best handled by specialists with expertise in opiate dependence, they noted.

Irritable bowel syndrome

The authors also described the use of Viberzi (eluxadoline, Allergan), a mixed opioid receptor agonist and antagonist, for treating diarrhea-predominant irritable bowel syndrome (IBS-D), including abdominal pain. They identify FDA recommended contraindications on the use of eluxadoline in clinical practice. Further, they emphasized that while mu opioid agonists like Imodium (loperamide, Johnson and Johnson) can treat diarrhea in IBS patients, there is no evidence for their use in treating chronic pain in these patients.

Camilleri and colleagues concluded that with 4% of adults in the U.S. taking chronic opioid therapy, “it is imperative to consider whether any presentation with gastrointestinal symptoms may be related to the intake of opioids.” – by Adam Leitenberger

Disclosures: Camilleri reports he has served as a consultant for AstraZeneca and as an advisory board member for Shionogi. Please see the full review for a list of all other authors’ relevant financial disclosures.

Michael Camilleri, MD
Michael Camilleri

A new American Gastroenterological Association Clinical Practice Update provides guidance on managing the gastrointestinal symptoms and side effects of opioids.

Michael Camilleri, MD, of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., and co-authors emphasized that considering the widespread use of opioids in the U.S., gastroenterologists should understand the beneficial or adverse effects these medications can have on the GI tract, and how to prevent and effectively treat them.

“Opioids are frequently encountered in clinical practice either as cause of patients’ symptoms or as the treatment for symptoms,” Camilleri told Healio Gastroenterology and Liver Disease. “Opioids have pharmacological effects on the entire gastrointestinal tract from the lower esophageal sphincter to the anorectum, and including the gall bladder and biliary tract.”

As opioid receptors are densely populated in the GI tract, patients taking opioids commonly experience conditions like opioid-induced constipation (OIC), esophageal dysmotility, delayed gastric emptying, and a unique condition called narcotic bowel syndrome, the authors wrote.

“Increasingly, the opioid epidemic is manifested in patients seen in gastroenterology practice as OIC and narcotic bowel syndrome,” Camilleri said. “Clinical guidelines on treatment of these conditions are available and help optimize patient management.”

Opioid-induced constipation

OIC is caused by mu opioids increasing fluid absorption and inhibiting colonic motility, and is generally defined as a change in bowel habits and defecation patterns after a patient starts taking opioids, Camilleri and colleagues wrote. The condition is characterized as having fewer than three weekly spontaneous bowel movements, straining, sensing incomplete evacuation and harder stool consistency. The authors noted that even low doses of opioids can cause OIC, and it can occur any time after a patient begins taking opioids.

Regarding prevention and treatment strategies for OIC, they recommended that laxatives should be a first-line treatment, or even be given prophylactically, although this is rarely done. If laxatives provide insufficient clinical benefit, they advised that prescription OIC treatments should be considered. These include Amitiza (lubiprostone, Sucampo/Takeda), Relistor (methylnaltrexone, Salix Pharmaceuticals), and Movantik (naloxegol, AstraZeneca). The FDA also recently approved Symproic (naldemedine, Shionogi/Purdue) for OIC, but this was not included in the article as it was not available for prescription at the time the article was submitted for publication.

Camilleri and colleagues also mentioned that naloxone, the IV drug used to treat opioid overdoses, has been shown to improve OIC symptoms when taken orally, and suggested that using Nucynta (tapentadol, Ortho-McNeil-Janssen Pharmaceuticals) or Targiniq ER (Purdue Pharma), a fixed-dose combination of oxycodone and naloxone, as alternatives to other opioids may be effective, as they have fewer GI adverse effects.

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Narcotic bowel syndrome

The authors also described narcotic bowel syndrome, which involves persistent moderate-to-severe abdominal pain occurring daily for more than 3 months in patients taking more than 100 mg of morphine equivalent per day. In this syndrome, the abdominal pain does not respond to narcotics, and may even intensify in response to increasing doses.

While the underlying mechanisms of narcotic bowel syndrome remain unclear, it differs from general causes of pain in those taking opiates “because it is a disease of nociception independent of the opioid effects on gut motility and secretion,” Camilleri and colleagues wrote.

Unfortunately, treatment is difficult, and requires detoxification and substitution of opioids, which is best handled by specialists with expertise in opiate dependence, they noted.

Irritable bowel syndrome

The authors also described the use of Viberzi (eluxadoline, Allergan), a mixed opioid receptor agonist and antagonist, for treating diarrhea-predominant irritable bowel syndrome (IBS-D), including abdominal pain. They identify FDA recommended contraindications on the use of eluxadoline in clinical practice. Further, they emphasized that while mu opioid agonists like Imodium (loperamide, Johnson and Johnson) can treat diarrhea in IBS patients, there is no evidence for their use in treating chronic pain in these patients.

Camilleri and colleagues concluded that with 4% of adults in the U.S. taking chronic opioid therapy, “it is imperative to consider whether any presentation with gastrointestinal symptoms may be related to the intake of opioids.” – by Adam Leitenberger

Disclosures: Camilleri reports he has served as a consultant for AstraZeneca and as an advisory board member for Shionogi. Please see the full review for a list of all other authors’ relevant financial disclosures.