GASTROENTEROLOGY/HEPATOLOGY

William D. Chey, M.D., led research at U-M that resulted in FDA approval of a novel drug for treatment of opioid-induced constipation.

Comfort zone

Naloxegol now approved for the treatment of adults with opioid-induced constipation

issue 23 | spring 2015

Research led by gastroenterologist William D. Chey, M.D., professor of Internal Medicine at U-M, recently resulted in the U.S. Food and Drug Administration's approval of naloxegol (Movantik, AstraZeneca Pharmaceuticals). The peripherally acting opioid receptor antagonist for the treatment of opioid-induced constipation in adults is on track for spring 2015 availability.

In the United States alone, more than 240 million opioid prescriptions are written annually. Of those on long-term opioid therapy, an estimated 40 to 90 percent of patients suffer opioid-induced constipation (OIC).

"Symptoms can range from a little nuisance to significant disability that makes functioning difficult — and may even cause some patients to discontinue their opioid therapy," Chey stresses. "For many patients, that makes naloxegol an important advancement, since it does not interfere with the narcotic's analgesic properties, but it does inhibit the gastrointestinal tract side effects."

Opioids work by binding to mu-receptors in the brain, blocking the brain's ability to perceive pain. However, opioids also bind to mu-receptors in the bowel, which is what causes OIC. Naloxegol limits the effects of opioids on the gastrointestinal tract without impacting the opioid receptors in the brain.

Naloxegol's safety and effectiveness was determined in two Phase III studies, both funded by AstraZeneca Pharmaceuticals and designed, executed and interpreted with the assistance of Chey and his team. The studies included 1,352 adult participants who had taken opioids for at least four weeks for non-cancer-related pain and had OIC. Participants were randomly assigned to receive 12.5 mg or 25 mg of naloxegol or placebo daily for 12 weeks.

In the first trial, 44 percent of participants receiving 25 mg of naloxegol and 41 percent of those receiving 12.5 mg of naloxegol experienced an increase in the number of bowel movements per week, compared with 29 percent of participants receiving placebo. The second trial showed similar results. Naloxegol's most commonly reported side effects were abdominal pain, diarrhea, nausea, vomiting and flatulence, all of which appear to be dose-related, as side effects occurred more commonly in the 25 mg group.

Chey offers a word of caution concerning naloxegol. "Constipation is a generic symptom for which there are many causes. So it's important to get a patient's medical history. If someone did not have constipation before starting prescription opioid pain medicines, then naloxegol is an excellent place to start. If, however, the patient has a history of constipation, you may not be looking at true opioid-induced constipation and naloxegol may not be the solution."