New guidelines for the treatment of opioid-induced constipation recommend peripherally-acting mu-opioid receptor antagonist (PAMORA) drugs, such as naloxegol (Movantik) in patients who do not respond to laxatives.

The clinical guidelines released by the American Gastroenterology Association, make evidence-based recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Developed in response to the growing use of opioids in the US, the guidelines presume that patients have been appropriately diagnosed and that they have either a prolonged requirement or dependence on opioids.

Before using laxatives or drugs to manage opioid-induced constipation the guideline recommends that physicians  ensure that patients are on the lowest possible dose of opioids needed. There may also be benefit in “opioid switching” to a less constipating formulation.

Traditional laxatives are recommended as first-line agents, with  mu-opioid receptor antagonists reserved for second line treatment.

The guideline authors say this class of drugs has shown to improve bowel symptoms without compromise to pain relief, although there can be associated side effects, including diarrhoea and abdominal pain.

For intestinal secretagogues such as lubiprostone and selective 5HT agonists such as prucalopride, the quality of evidence is low and therefore the AGA makes no recommendation.

“Opioid overuse has become a public health crisis in America. What the public often doesn’t hear about are just how common gastrointestinal side effects, especially constipation, are in opioid users,” says Dr Seth D. Crockett, lead author of the guidelines, University of North Carolina School of Medicine, Chapel Hill.

“Physicians have struggled with treating this condition due to previous lack of clinical guidance. The new AGA guideline clarifies existing data and provides clear direction for physicians on how to best treat opioid-induced constipation.”

Opioid-induced constipation is estimated to affect 40-60% of patients taking chronic opioid therapy, and up to 5% of Americans are currently taking opioids regularly.

The guidelines define opioid-induced constipation as, “a change when initiating opioid therapy from baseline bowel habits that is characterised by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool frequency.”

The guideline focuses on the medical management of opioid-induced constipation and does not address the role of psychological therapy, alternative medicine approaches, surgery or devices.

In Australia, guidelines for opioid-induced constipation refer only to oral and rectal laxatives.

For medical management of opioid-induced constipation (OIC), the AGA guidelines are:

1. In patients with OIC, the AGA recommends use of laxatives as first-line agents. Strong recommendation, moderate-quality evidence
2. In patients with laxative refractory OIC, the AGA recommends naldemedine over no treatment. Strong recommendation, high-quality evidence.
3. In patients with laxative refractory OIC, the AGA recommends naloxegol over no treatment. Strong recommendation, moderate-quality evidence
4. In patients with laxative refractory OIC, the AGA suggests methylnatrexone over no treatment. Conditional recommendation, low-quality evidence
5. In patients with OIC, the AGA makes no recommendation for the use of lubiprostone. No recommendation, evidence gap.
6. In patients with OIC, the AGA makes no recommendation for the use of prucalopride. No recommendation, evidence gap