FDA Warning on Eluxadoline (Viberzi)

Briefly noted: The FDA has issued a safety warning for patients with irritable bowel syndrome who have had their gallbladder removed.

FDA Warns of Increased Risk of Serious Pancreatitis with irritable bowel drug eluxadoline (Viberzi) in patients without a gallbladder

An excerpt:

Viberzi is a prescription medicine used to treat irritable bowel syndrome in adults when the main symptom is diarrhea (IBS-D)…From May 2015, when Viberzi was first approved, through February 2017, FDA received 120 reports of serious cases of pancreatitis or death.* Among the 68 patients who reported their gallbladder status, 56 of them did not have a gallbladder and received the currently recommended dosage of Viberzi. Seventy-six patients were hospitalized, of which two patients died.

My take: Now that this warning has been issued, there may be additional cases identified. While this medication is mainly used in adults, pediatric gastroenterologists need to be aware of this risk in counseling potential patients.

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Eluxadoline for Irritable Bowel Syndrome with Diarrhea

A recent study (AJ Lembo et al. NEJM 2016; 374: 242-53) found that eluxadoline, an oral agent with mixed opioid effects was helpful in some with irritable bowel syndrome with diarrhea (IBS-D).

Study methods: 2427 adults with IBS-D received either 75 mg, 100 mg of study medication or placebo twice daily for 26 weeks.  The primary endpoint was a composite response of decreased abdominal pain and stool consistency.

Eluxadoline in IBS

Eluxadoline in IBS.  Primary efficacy end point was defined as the proportion of patients who recorded a reduction of 30% or more from baseline in the daily average score for their worst abdominal pain for at least 50% of days assessed and, on the same days, a daily stool consistency score of less than 5.  Panel A: weeks 1-12.  Panel B for weeks 1-26.

While the absolute difference in response compared to placebo appears modest (see Figure above), the authors note that the treatment effects “were similar to those reported with alosetron and rifaximin.” Adverse effects included nausea (7.5% in 100 mg group compared with 5.1% in placebo), constipation (8.6%% in 100 mg group compared with 2.5% in placebo), and abdominal pain (7.2% in 100 mg group compared with 4.1% in placebo).  Pancreatitis developed in 5 patients in the treatment group (0.3%).

My take: While Eluxadoline helped some with IBS-D, better, more effective treatments are needed.

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FDA Approves Rifaximin and Eluxadoline for IBS-D

From FDA (5/27/15): Two New FDA-Approved Treatments for adults with IBS-D

Excerpt:

The U.S. Food and Drug Administration today approved Viberzi (eluxadoline) and Xifaxan (rifaximin), two new treatments, manufactured by two different companies, for irritable bowel syndrome with diarrhea (IBS-D) in adult men and women….

“For some people, IBS can be quite disabling, and no one medication works for all patients suffering from this gastrointestinal disorder,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in FDA’s Center for Drug Evaluation and Research. “The approval of two new therapies underscores the FDA’s commitment to providing additional treatment options for IBS patients and their doctors.”

Viberzi, which contains a new active ingredient, is taken orally twice daily with food. Viberzi activates receptors in the nervous system that can lessen bowel contractions. Viberzi is intended to treat adults with IBS-D.

Xifaxan can be taken orally three times a day for 14 days, for the treatment of abdominal pain and diarrhea in patients with IBS-D. Patients who experience a recurrence of symptoms can be retreated with a 14 day treatment course, up to two times. Xifaxan, an antibiotic derived from rifampin, was previously approved as treatment for travelers’ diarrhea caused by E. coli and for reduction of the risk in adult patients of recurring overt hepatic encephalopathy, the changes in brain function that occur when the liver is unable to remove toxins from the blood. The exact mechanism of action of Xifaxan for treatment of IBS-D is not known, but is thought to be related to changes in the bacterial content in the gastrointestinal tract.

The safety and effectiveness of Viberzi for treatment of IBS-D were established in two double-blind, placebo-controlled clinical trials…Results showed Viberzi was more effective in simultaneously reducing abdominal pain and improving stool consistency than placebo over 26 weeks of treatment.

The safety and effectiveness of Xifaxan for treatment of IBS-D were established in three double-blind, placebo-controlled trials.

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