Eluxadoline (Truberzi▼): risk of pancreatitis; do not use in patients who have undergone cholecystectomy or in those with biliary disorders

Cases of pancreatitis, with or without sphincter of Oddi spasm, have been reported in patients taking eluxadoline. Some cases have resulted in hospitalisation and death, primarily in patients who have undergone cholecystectomy.

Advice for healthcare professionals:

  • eluxadoline (Truberzi▼), licensed for irritable bowel syndrome with diarrhoea, should be initiated and supervised by a specialist physician experienced in diagnosis and management of gastrointestinal disorders

  • do not use in patients without a gallbladder or in patients with known or suspected biliary tree or pancreatic duct obstruction (eg, gallstones, tumour, periampullary duodenal diverticulum) or sphincter of Oddi disease or dysfunction

  • tell patients to avoid drinking alcohol during treatment with eluxadoline

  • inform patients about symptoms suggestive of pancreatitis—eg, abdominal pain that may radiate to the back or shoulder, nausea, and vomiting

  • instruct patients to stop taking eluxadoline and seek immediate medical attention if these symptoms develop

  • report all suspected adverse drug reactions to Black Triangle drugs such as Truberzi to the Yellow Card Scheme

Background

Eluxadoline (Truberzi▼) was approved in 2017 for the treatment of irritable bowel syndrome with diarrhoea (IBS-D) in adults.

On 30 August 2017, the National Institute of Health and Care Excellence (NICE) recommended that eluxadoline could be prescribed on the NHS in England if other pharmacological treatments for IBS-D did not work or were unsuitable and if it was started in secondary care. Use of eluxadoline in the UK is so far extremely low (it is approximated that no more than 20 patients in the UK have started the medicine).

Cases of pancreatitis in patients taking eluxadoline

A routine European review identified 230 cases of, or reactions suggestive of, pancreatitis in patients taking eluxadoline over an estimated exposure of 26,363 patient-years. All cases of pancreatitis came from the USA where, before April 2017, a contraindication in patients without a gallbladder was not in place. Gallbladder status was known in 140 of the cases and of these, most (76%) had undergone cholecystectomy and did not have a gallbladder. Of these, 4 cases were severe: 2 cases in which eluxadoline appears to have contributed to the patient’s death, 1 case of necrotising pancreatitis with an unknown outcome, and 1 case involving acute kidney injury due to dehydration and acute respiratory insufficiency due to atelectasis, which were suspected to have been secondary to pancreatitis. Dehydration and pulmonary complications of acute pancreatitis have been reported in the literature.

Most of the reported cases of pancreatitis occurred within 1 week of starting treatment with eluxadoline and some patients developed symptoms even after 1 to 2 doses. However, cases of pancreatitis after longer duration of treatment have also been reported.

In most cases, eluxadoline treatment was withdrawn. At the time of review, out of the reports with an outcome reported (123 reports), most patients (107) had recovered from the pancreatitis or their condition was improving.

Actions taken following review

A letter has been sent to healthcare professionals on this issue and the product information (Summary of Product Characteristics and Patient Information Leaflet) has been updated to include the above warnings and new contraindications, as well as to add a restriction that therapy with eluxadoline should be initiated and supervised by a physician experienced in diagnosis and management of gastrointestinal disorders.

Consult the full list of contraindications in the Summary of Product Characteristics before prescribing eluxadoline.

Article citation: Drug Safety Update volume 11 issue 5; December 2017: 4.

Published 14 December 2017