Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome

Özdener, Ayşe Elif; Rivkin, Anastasia

doi:10.2147/dddt.s127405

Cited by 14 publications

(21 citation statements)

References 27 publications

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“…It is believed to decrease visceral hypersensitivity without completely inhibiting GI motility as compared to selective mu receptor agonists [4]. Mu receptor agonism improves abdominal pain and diarrhea in IBS-D by decreasing GI motility and visceral hypersensitivity whereas delta receptor antagonism prevents mu receptor-mediated unopposed inhibition of GI motility and prevents constipation while enhancing mu receptor mediated analgesia [5-6].…”

Section: Discussionmentioning

confidence: 99%

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Eluxadoline-induced Recurrent Pancreatitis in a Young Female without a Gallbladder: A Case Report and Literature Review

Khetpal¹,

Yadav²,

Khalid³

et al. 2018

Cureus

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Eluxadoline is a mixed opioid receptor agonist and antagonist approved for the treatment of diarrhea-predominant irritable bowel syndrome (IBS). It is believed to decrease visceral hypersensitivity without completely inhibiting intestinal motility. Pooled safety data from two phase three randomized trials have reported few cases of pancreatitis especially in patients with sphincter of Oddi (SO) dysfunction and cholecystectomy patients. We present a rare case of eluxadoline-induced recurrent pancreatitis in a 31-year-old female without a gallbladder. Her medical history was significant for irritable bowel syndrome with diarrhea (IBS-D), cholecystectomy, and depression. She was started on 75 mg of eluxadoline (the recommended dose for IBS-D patients without a gallbladder) three weeks prior to the first episode of pancreatitis. She had a recurrent episode of pancreatitis after few weeks and her symptoms and lipase levels improved significantly two days after stopping eluxadoline. The exact mechanism of eluxadoline to cause pancreatitis is unknown but it is believed to increase SO contractions. The absence of gallbladder prevents cholecystokinin mediated relaxation of the SO thus contributing more to spasms with eluxadoline. Few cases of severe pancreatitis and death have been reported even with the reduced dose of eluxadoline recommended for cholecystectomy patients. This case highlights the importance of considering drug-induced pancreatitis and avoidance of eluxadoline even in reduced doses in patients without a gallbladder.

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Section: Discussionmentioning

confidence: 99%

“…From weeks 1 through 26, only the 100-mg arm performed significantly better than placebo in the primary endpoint in IBS-3001. Both 75 mg and 100 mg groups performed significantly better than placebo in the IBS-3002 trial through week 26 [1,6].…”

Section: Discussionmentioning

confidence: 99%

Eluxadoline-induced Recurrent Pancreatitis in a Young Female without a Gallbladder: A Case Report and Literature Review

Khetpal¹,

Yadav²,

Khalid³

et al. 2018

Cureus

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“…Cholestyramine is the medication of choice in patients with IBS-D with proven malabsorption of bile acids 69 . Eluxadoline is a locally acting, mixed mu opioid receptor (μOR) agonist/delta opioid receptor (δOR) antagonist with low oral bioavailability, with a proposed indication in adults for the treatment of IBS-D. Eluxadoline is a new therapeutic agent that reduced symptoms of IBS with diarrhea, with sustained efficacy over 6 months in patients who received the 100-mg dose twice daily 70 . However, Eluxadoline may increase the risk of the pancreatitis in patients with heavy alcohol use 71,72 .…”

Section: Laxativesmentioning

confidence: 99%

“…This may make rifaximin a possible initial or second-line treatment option for patients with IBS-D (ref. 70,86 ). It is necessary that further studies prove the efficacy of Corticosteroids, Mast cell stabilizers and Mesalazine for IBS therapy 86 .…”

Section: Anti-inflammatory Therapiesmentioning

confidence: 99%

Irritable bowel syndrome - from etiopathogenesis to therapy

Radovanović-Dinić¹,

Tešić-Rajković²,

Grgov³

et al. 2018

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Irritable bowel syndrome (IBS) is a chronic and relapsing functional gastrointestinal disorder that affects 9-23% of the population across the world. Patients with IBS are often referred to gastroenterology, undergo various investigations, take various medicines, take time off work and have a poor quality of life. The pathophysiology of IBS is not yet completely understood and seems to be multifactorial. Many pathogenetic factors, in various combinations, and not all necessarily present in each patient, can play an important role. Discomfort or abdominal pain relieived by defacation, asociated with a change in stool form, is a typical clinical manifestation of IBS. Many factors, such as emotional stress and eating, may exacerbate the symptoms. A timely diagnosis of IBS is important so that treatment which will provide adequate symptomatic relief (diarrhoea, constipation, pain and boaring) can be introduced. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria IV is the current gold-standard for the diagnoses of IBS. Treatment of patients with IBS requires a multidisciplinary approach. Some patients respond well to non-pharmacological treatment, while others also require pharmacological treatment. This review will provide a summary of pathophysiology, diagnostic criteria and therapies for IBS.

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“…Eluxadoline is a mixed mu-opioid receptor agonist with delta-opioid receptor antagonist activity and kappa-opioid agonist. Lomotil (diphenoxylate and atropine) have opioid and anticholinergic activity [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Cardiac Dysrhythmia Associated With Opioid Toxicity

Rawala

Gulati

Rizvi

2020

Cureus

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder involving abnormal motility. The patients are commonly started on symptom control management for IBSdiarrhea subtype by prescribing antimotility agents, usually having opioid agonist activity, and newer medications have been emerging for this as well. Patients sometimes self-medicate themselves to exceedingly high doses of these medications to achieve symptoms control. There are only a few cases of opioid-induced arrhythmia in the literature, primarily loperamide being used as a drug substitute by substance abusers. Still, it has been rarely reported to cause arrhythmia in a patient with IBS. We present a case of a 33-year-old female with a past medical history of hypertension and depression who presented to the emergency department for evaluation of syncope. She had wide complex tachycardia on electrocardiogram (EKG) with prolonged rate-corrected QT interval (QTc). Her medications, including eluxadoline, Lomotil, and loperamide, were held and she was discharged on mexiletine with normal QTc. She did not have any more incidences of arrhythmia. This case highlights the importance of not overdosing on opioid agonist medications prescribed to treat IBS as these can lead to potentially fatal complications. Physicians have to be judicious in promptly determining that the cause of arrhythmia can also be over-the-counter (OTC) medications.

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Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome

Cited by 14 publications

References 27 publications

Eluxadoline-induced Recurrent Pancreatitis in a Young Female without a Gallbladder: A Case Report and Literature Review

Eluxadoline-induced Recurrent Pancreatitis in a Young Female without a Gallbladder: A Case Report and Literature Review

Irritable bowel syndrome - from etiopathogenesis to therapy

Cardiac Dysrhythmia Associated With Opioid Toxicity

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