FDA Okays Naloxegol (Movantik) in Opioid-Induced Constipation

The US Food and Drug Administration (FDA) has approved naloxegol (Movantik, AstraZeneca Pharmaceuticals), a peripherally acting opioid receptor antagonist, for the treatment of opioid-induced constipation (OIC) in adults with chronic noncancer pain.

OIC is a common adverse effect of opioid use. An estimated 40% to 80% of patients receiving long-term opioid therapy experience OIC, which can be severe enough to cause discontinuation of opioid therapy.

The problem is caused by binding of opioids to peripheral opioid receptors in the gastrointestinal (GI) tract, resulting in absorption of electrolytes, such as chloride, with a subsequent reduction in small intestinal fluid. Activation of enteric opioid receptors also results in abnormal GI motility.

“Supportive care products such as Movantik can lessen the constipating side effects of opioids,” said Julie Beitz, MD, director, Office of Drug Evaluation, FDA’s Center for Drug Evaluation and Research, in an FDA statement.

The safety and effectiveness of naloxegol were established in 2 multicenter clinical trials of 1352 adult participants who had taken opioids for at least 4 weeks for non–cancer-related pain and had opioid-induced constipation. At least 50% of the patients had an inadequate response to laxatives.

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% of participants receiving 25 mg of naloxegol and 41% of those receiving 12.5 mg of naloxegol experienced an increase in number of bowel movements per week, compared with 29% of participants receiving placebo. The second trial showed similar results.

The most common adverse effects with treatment included abdominal pain, diarrhea, headache, and excessive gas in the stomach or intestinal area.

The FDA is requiring a postmarketing study to further evaluate the potential risk for cardiovascular adverse events in patients taking naloxegol. In June, the FDA held a public meeting to discuss what studies might be required to assess the cardiac safety of peripherally acting opioid receptor antagonists, including this one, intended to treat OIC.

Last year, the FDA approved lubiprostone (Amitiza, Sucampo Pharmaceuticals Inc/Takeda Pharmaceuticals USA Inc), the first oral treatment for OIC in adults with chronic noncancer pain. The drug is a specific activator of CIC-2 chloride channels in the intestinal epithelium and bypasses the antisecretory action of opiates by activation of apical CIC-2 channels.

Approval was based on results from 12-week phase 3 studies in patients taking opioids, including morphine, oxycodone, and fentanyl, for chronic noncancer pain and from a long-term open-label safety study.

In a statement, AstraZeneca notes that Movantik is expected to be available to patients in the first half of 2015.

“During the review of the New Drug Application, the FDA evaluated the abuse potential of Movantik and the approved labelling indicates that Movantik has no risk of abuse or dependency,” the company notes in a statement. “AstraZeneca submitted a petition for the descheduling of Movantik to the US Drug Enforcement Administration (DEA) in March 2012, which was accepted for review and will be considered by the DEA as part of the process for addressing the descheduling request.”