Page 26 - Delaware Medical Journal - March 2017
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Eluxadoline-Associated Pancreatitis in a Post-Cholecystectomy Patient: A Case Report
Anuj Chhaparia, MD; Muhammad B. Hammami, MD; Ashley Vareedayah, MD; Katie Schroeder, MD
Eluxadoline has emerged as
an effective treatment option
for patients with diarrhea- predominant irritable bowel syndrome (IBS-D). It was approved by the Food and Drug Administration (FDA) in May 2015 for treatment of IBS-D. It is a μ-opioid receptor agonist and δ-receptor antagonist that acts locally in the gastrointestinal
(GI) tract. In recently published phase III IBS-3001 and IBS-
3002 trials, eight patients experienced abdominal pain due to sphincter of Oddi dysfunction (SOD), and one patient had acute pancreatitis, thought to be related to eluxadoline. Here, we describe
a patient with eluxadoline-
induced pancreatitis, the first
case we know of to be reported outside of phase III clinical trials. Interestingly, only patients with prior cholecystectomy developed SOD and acute pancreatitis in the IBS 3001/3002 trials which also stands true with our patient. The enthusiasm with the efficacy of this drug should not have clinicians disregard the potential adverse effects, particularly serious ones, such as acute pancreatitis. We expect more cases of eluxadoline- induced pancreatitis and SOD
to be reported, and future studies should focus on better understanding this association so as to guide treatment recommendations.
Introduction
Irritable bowel syndrome (IBS) is a common entity encountered in clinical practice. Prevalence of IBS in the United States has been estimated to be between
5 percent and 9.9 percent.1 burden of IBS is enormous, with about
5.9 million IBS-related prescriptions reported in 2004.2 Patients with IBS present with abdominal pain or discomfort associated with alternating bowel habits. based on stool consistency. According
to the Rome III criteria, patients with
bowel movements or hard lumpy stools
with diarrhea (IBS-D).3 Pharmacologic therapy for IBS-D includes anti-diarrheal (e.g. Loperamide), anti-spasmodics (e.g. Dicyclomine) and 5-HT3 antagonists (e.g. Alosetron: approved for women with refractory IBS-D). The latest addition
to this list is eluxadoline. Eluxadoline
was FDA-approved for the treatment of IBS-D in May 2015.4 Eluxadoline has a divergent effect on various opioid receptors — it works as an agonist at the μ-opioid receptor.4 Activation of μ-opioid receptors in the gastrointestinal (GI) tract decreases peristalsis, delays passage of contents through the bowel, and thus increases 5 Interestingly, there
is evidence suggesting that antagonism of
binding and signaling, and concurrently decreases the tolerance or dependence associated with μ-agonists.6 Thus, the is a desirable one. Eluxadoline exerts these effects locally in the GI tract. Research has shown that bioavailability of eluxadoline
is poor in humans (1.02 percent) due to combination of low GI absorption and high 7
eluxadoline in IBS-D patients is exciting. In recently published IBS 3001 and IBS 3002 phase III clinical trials, patients who received eluxadoline (75mg or 100mg) had both abdominal pain and diarrhea, when compared to patients who received placebo. The most common side effects reported
in these trials were nausea, constipation, and abdominal pain.8 However, the most concerning side effect associated with eluxadoline is acute pancreatitis. In phase II randomized clinical trials, 807 patients were randomly assigned to twice daily doses of placebo, 5 mg, 25 mg, 100 mg, or 200 mg
of eluxadoline for 12 weeks. A total of four patients developed acute pancreatitis, three during the treatment period and one (in the 100 mg group) approximately 15 days after the treatment period. Two patients had acute pancreatitis in the 200 mg group; however, it must be noted that one of these patients had a positive blood ethanol level at the time of the event, along with a history of alcoholic pancreatitis. One patient developed acute pancreatitis with twice daily 25 mg dosing.
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Del Med J | March 2017 | Vol. 89 | No. 3
Abstract
