Increased risk of serious pancreatitis with Eluxadoline in patients without a gallbladder

ADR Bulletin, by Shinu.C

Increased risk of serious pancreatitis with Eluxadoline in patients without a gallbladder

Eluxadoline is approved for use in adults for the treatment of irritable bowel syndrome with diarrhea (IBSD). It is a tablet taken by mouth twice a day with food. It works by activating opioid receptors in the gut to decrease bowel contractions, which leads to less diarrhea. It can also help to ease stomach-area or abdomen pain and improve stool consistency. It is a controlled substance (CIV) and may be abused or lead to drug dependence. Alcohol and other diarrhea medicines should be avoided while taking the drug. Use the drug along with lifestyle changes, such as limiting foods that aggravate your symptoms, eating more slowly and not overeating, and avoiding carbonated drinks, which can lead to gas and cramping. Common side effects of the medicine include constipation, nausea, and stomach-area or abdomen pain.

FDA is warning that eluxadoline should not be used in patients who do not have a gallbladder. An FDA review found these patients have an increased risk of developing serious pancreatitis that could result in hospitalization or death. Pancreatitis may be caused by spasm of a certain digestive system muscle in the small intestine. Eluxadoline is a prescription medicine used to treat irritable bowel syndrome in adults when the main symptom is diarrhea (IBS-D). IBS-D affects the large intestine and causes cramping, stomacharea or abdomen pain, bloating, gas, and diarrhea. The cause of IBS-D is not known. It works by decreasing bowel contractions, which leads to less diarrhea. In patients with IBS-D, the drug  can help ease stomach-area or abdomen pain and improve stool consistency.

Studies from May 2015 to 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 drug. Seventy-six patients were hospitalized, of which two patients died. These two patients did not have a gallbladder. Some cases of serious pancreatitis or death also reported sphincter of Oddi spasm (n=6) or abdomen pain (n=16)

ADDITIONAL INFORMATION TO PATIENTS •Patients who do not have a gallbladder should not take eluxadoline. •Patients who do not have a gallbladder who are taking eluxadoline have an increased risk of developing new or worsening stomach-area or abdomen pain due to pancreatitis with or without sphincter of Oddi spasm. •Hospitalizations related to pancreatitis, including deaths, have been reported with eluxadoline in patients who do not have a gallbladder. •Stop taking the drug right away and get emergency medical care if you develop new or worsening stomach-area or abdomen pain, or pain in the upper right side of your stomach-area or abdomen that may move to your back or shoulder, with or without nausea and vomiting. •Talk to your health care professional before you take any over-the-counter (OTC) medicines to treat diarrhea, constipation, or other problems with your bowels or colon, can cause severe constipation. •Before starting treatment with eluxadoline, patients should tell their health care professional if they: •Have no gallbladder •Have or may have had a blockage in your gallbladder or a sphincter of Oddi problem •Have had inflammation of your pancreas

•Have serious liver problems •Have a history of chronic constipation •Have or may have had a bowel blockage •Have a habit of drinking more than three alcoholic beverages a day •Lifestyle changes, such as limiting foods that aggravate your symptoms, eating more slowly and not overeating, and avoiding carbonated drinks which can lead to gas and cramping, can help reduce the symptoms of IBS-D. •Report side effects from the drug.

ADDITIONAL INFORMATION TO HEALTH CARE PROFESSIONAL •Pancreatitis with and without sphincter of Oddi spasm can occur even after the first or second dose of drug, independent of gallbladder status. •Do not use the drug in the following patients: •Who do not have a gallbladder •Have or may have had a blockage of the gallbladder or a sphincter of Oddi problem •Have had pancreatitis or other pancreas problems, including a blockage of the pancreas •History of serious liver problems •History of chronic or severe constipation •Have or may have had intestinal obstruction •History of alcohol abuse, alcohol addiction, or drinks more than three alcoholic beverages a day •Counsel patients on managing stress and making changes in diet and lifestyle to help control symptoms of IBS-D. •Tell patients to talk with a health care professional before taking any anti-diarrhea medicine, including over-the-counter medicines. •Report adverse events of eluxadoline.