Two new choices for patients with IBS-D
Eluxadoline (Viberzi—Patheon), a novel medication, and rifaximin (Xifaxan—Salix), a previously approved agent, have received FDA approval for the treatment of adult patients with irritable bowel syndrome with diarrhea (IBS-D). The condition affects an estimated 15 million patients in the United States, with women twice as likely as men to have IBS-D.
New indication for rifaximin
Rifaximin was previously approved for the treatment of travelers’ diarrhea caused by noninvasive strains of Escherichia coli in adult and pediatric patients 12 years of age and older, and for the reduction in risk of overt hepatic encephalopathy recurrence in adults. The recommended dose of rifaximin for IBS-D is one 550-mg tablet three times a day for 14 days, with a repeat regimen recommended for patients who experience recurrence. Patients can be retreated up to two times with the same regimen of rifaximin. The following content will focus on eluxadoline, since it is a novel agent.
Eluxadoline is a mu-opioid receptor agonist that interacts with opioid receptors in the gut. In addition, this agent has delta opioid receptor antagonist and kappa opioid receptor agonist activity. Currently, it is classified as a controlled substance; however, the specific schedule is still pending. Two human abuse–potential studies have shown that eluxadoline can cause more feelings of euphoria and positive subjective measures such as “drug liking” and “high” compared with placebo.
Clinical data. Approval of eluxadoline was based on data from two large, 26-week, double-blind, placebo-controlled studies that included more than 2,400 patients with Rome III criteria for IBS-D.
Eligible patients were those with loose or watery stools 25% of the time or more, and hard or lumpy stools less than 25% of the time. In addition, patients were required to have an average worst abdominal pain score in the past 24 hours of greater than 3 on a 0–10 scale over the week prior to randomization, and an average daily stool consistency score of 5.5 or more and at least 5 days with a score of 5 or more on a 1–7 scale over the week prior to randomization.
In both studies, eluxadoline demonstrated significant superiority over placebo on the overall composite responder primary endpoint, defined as simultaneous improvement in abdominal pain and diarrhea at both the 75-mg and 100-mg twice-daily doses. After 12 weeks, composite responses ranged from 24% to 30% for eluxadoline doses compared with 16% to 17% for placebo. After 26 weeks, composite responses ranged from 23% to 33% for eluxadoline doses compared with 19% to 20% for placebo.
Adverse events. Constipation (7% to 8% for eluxadoline vs. 3% for placebo) and nausea (7% to 8% for eluxadoline vs. 5% for placebo) were the most common adverse events in the two trials. Severe constipation was rare, occurring in less than 1% of patients receiving eluxadoline.
Drug class: Mu-opioid receptor agonist
Indication: Adult patients with irritable bowel syndrome with diarrhea
Dosage: 100 mg twice daily with food
- An initial dose of 75 mg twice daily is recommended for patients who do not have a gallbladder, are unable to tolerate the 100-mg dose, are receiving concomitant OATP1B1 inhibitors, or have mild or moderate hepatic impairment.
- Treatment should be stopped in patients who develop severe constipation for more than 4 days.
- Of note: Contraindications to therapy include known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction; alcoholism, alcohol abuse, or addiction or consumption of more than three alcoholic drinks per day; a history of pancreatitis or structural disease of the pancreas; severe hepatic impairment (Child–Pugh Class C); or severe constipation or sequelae from constipation.
- Patients should be monitored closely for sphincter of Oddi spasm and pancreatitis. Assess patients for new or worsening abdominal pain, with or without nausea and vomiting, or acute biliary pain with liver or pancreatic enzyme elevations. Treatment should be discontinued if any of these symptoms occur; patients who experience them should contact their primary care provider.
Refer patients to the approved Medication Guide and counsel them on proper dosing (i.e., twice daily with food) and potential adverse events. Advise patients to avoid chronic or excessive alcohol use while taking eluxadoline. Explain that if they miss a dose, they should take the next dose at the regular time and not double up doses. Tell patients to stop taking eluxadoline if they experience unusual or severe abdominal pain or severe constipation for more than 4 days and to contact their primary care provider if they experience these symptoms.