146

Eluxadoline is a minimally absorbed µ-opioid receptor agonist and δ-opioid

receptor antagonist. Studies have shown that when there is simultaneous µ-opioid

receptor agonism and δ-opioid receptor antagonism, patients will experience

decreased abdominal pain and diarrhea.

147

The dosage approved for the treatment of IBS-D is 100 mg twice daily taken with

food, but the dose is reduced to 75 mg BID in patients who are unable to tolerate 100

mg BID, have no gallbladder, have mild to moderate liver impairment, or are on

organic anion transporting polypeptides (OATP1B1) inhibitors.

148 Patients treated

with eluxadoline had better clinical response in phase 2 trials with decreased

abdominal pain and increase stool consistency without significant risk of

constipation.

147 The most common side effects in patients treated with eluxadoline

include constipation, nausea, and abdominal pain.

148 The most serious known risk

associated with eluxadoline is the risk of sphincter of Oddi spasm, which can result

in pancreatitis. Eluxadoline should not be used in patients with a history of bile duct

obstruction, pancreatitis, severe liver impairment, or severe constipation, and in

patients who drink more than three alcoholic beverages daily.

148 Patients should be

counseled to avoid alosetron or loperamide in combination with eluxadoline on a

chronic basis, although it can be used on an acute as needed basis. If signs of

constipation occur, the patient must be advised to discontinue loperamide

immediately. They must discontinue eluxadoline if they experience constipation for

more than 4 days. Patients should also be advised to avoid concomitant use of

anticholinergics and other opioids with eluxadoline to avoid constipation. They

should be reminded that eluxadoline has a potential for drug abuse.

148

In L.K.’s case, initiation of loperamide 2 mg as needed before a stressful situation

would be a cost-effective approach to her symptoms. Should her symptoms worsen

or her current regimen lose effectiveness, eluxadoline 100 mg BID with food is an

alternative, while a course of rifaximin 550 mg TID for 14 days would be considered

an alternative strategy if she fails eluxadoline. The patient should be advised not to

combine these therapies for chronic treatment and discontinue eluxadoline if she

experiences constipation for 4 days.

p. 536

p. 537

KEY REFERENCES AND WEBSITES

A full list of references for this chapter can be found at

http://thepoint.lww.com/AT11e. Below are the key references and websites for this

chapter, with the corresponding reference number in this chapter found in parentheses

after the reference.

Key References

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Colombel JF et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med.

2010;362:1383. (74)

Hoentjen F et al. Update on the Management of Ulcerative Colitis. Curr Gastroenterol Rep. 2011;13:475. (19)

Ford A et al. “American College Gastroenterology Monograph on the Management of Irritable Bowel Syndrome

and Chronic Idiopathic Constipation” Am J Gastroenterol. 2014;109:S2–S26. (114)

Kornbluth A et al. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice

Parameters Committee. Am J Gastroenterol. 2010;105:501. (14)

Lichtenstein GR et al. American Gastroenterological Association Institute technical review on corticosteroids,

immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006;130: 940. (25)

Lichtenstein GR et al. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104:465. (16)

Pimentel M et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med.

2011;364: 22. (143)

Regueiro M et al. Clinical guidelines for the medical management of left-sided ulcerative colitis and ulcerative

proctitis:summary statement. Inflamm Bowel Dis. 2006;12:972. (22)

Talley NJ et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J

Gastroenterol. 2011;106(Suppl 1): S2–25; quiz S26. doi: 10.1038/ajg.2011.58. (3)

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