An Antiemetic for Irritable Bowel Syndrome? a Drug Used for Cancer Patients May Provide Some Relief to Patients with IBS

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An Antiemetic for Irritable Bowel Syndrome? A drug used for cancer patients may provide some relief to patients with IBS. Robert Levy, MD, Jason Corbo, PharmD, BCPS, Shailendra Prasad, MBBS, MPH

PRACTICE CHANGER habits: constipation (IBS-C), diar- colitis and severe constipation.12 Consider prescribing ondanse- rhea (IBS-D), or alternating peri- It was reintroduced in 2002 but tron (up to 24 mg/d) for patients ods of both—mixed (IBS-M).2 The can be prescribed only by clini- who have irritable bowel syn- diagnosis is based on Rome III cians who enroll in a prescribing drome with diarrhea (IBS-D).1 criteria, which include recurrent program provided by the manu- abdominal pain or discomfort on facturer, and there are restrictions STRENGTH OF at least three days per month in on its use. RECOMMENDATION the past three months associated Ondansetron—another 5-HT3 B: Based on a well-done double- with two or more of the following: receptor antagonist used to treat blind, placebo-controlled ran- improvement with defecation, nausea and vomiting caused by domized controlled trial (RCT).1 onset associated with a change chemotherapy—may be another in frequency of stool, and onset option for treating IBS-D. Garsed ILLUSTRATIVE CASE associated with a change in form et al1 recently conducted an RCT A 23-year-old woman who was (appearance) of stool.3 IBS often to evaluate the efficacy of ondan- diagnosed with irritable bowel is unrecognized or untreated, and setron for patients with IBS-D. syndrome (IBS) comes to your as few as 25% of patients with IBS clinic with complaints of in- seek care.4 STUDY SUMMARY creased frequency of defecation IBS-D affects approximately Ondansetron improves with watery stools and general- 5% of the general population in stool consistency, severity ized, cramping abdominal pain. North America.5,6 IBS-D is as- of IBS symptoms She also notes increased passage sociated with a considerably In a five-week, double-blind cross- of mucus and a sensation of in- decreased quality of life and is over RCT, Garsed et al1 compared complete evacuation. a common cause of work absen- ondansetron with placebo for She says the only thing that re- teeism.7,8 Because many condi- symptom relief in 120 patients who lieves her pain is defecation. She tions can cause diarrhea, patients met Rome III criteria for IBS-D. All has tried loperamide, acetamin- typically undergo numerous tests patients were ages 18 to 75 and ophen, and ibuprofen without before receiving an accurate di- had no evidence of inflammatory relief. She does not have Crohn agnosis, which creates a financial bowel disease. Exclusion criteria disease or ulcerative colitis. What burden.9 included pregnancy or breastfeed- else can you offer her that is safe For many patients, current IBS ing, unwillingness to stop antidiar- and effective? treatments—including fiber sup- rheal medication, prior abdominal plements, laxatives, antidiarrheal surgery other than appendectomy BS is a chronic, episodic func- medications, antispasmodics, and or cholecystectomy, or enrollment Itional gastrointestinal disorder antidepressants such as tricyclics in another trial. characterized by abdominal pain and selective serotonin reuptake Patients were started on on- or discomfort and altered bowel inhibitors—are unsatisfactory.10 dansetron 4 mg/d with dose ti- Alosetron, a 5-hydroxytryptamine tration up to 24 mg/d based on Robert Levy and Shailendra Prasad are 3 (5-HT3) receptor antagonist, has response; no dose adjustments in the North Memorial Family Medicine been used to treat IBS-D,11 but this were allowed during the last two Residency at the University of Minnesota, medication was voluntarily with- weeks of the study. There was a Minneapolis. Jason Corbo is in the Family Medicine Residency Program at UPMC St. drawn from the US market in 2000 two- to three-week washout be- Margaret in Pittsburgh. due to concerns about ischemic tween treatment periods.

16 Clinician Reviews • NOVEMBER 2014 clinicianreviews.com The primary endpoint was av- enced significantly fewer days of slight improvement in formed erage stool consistency in the last urgency and bloating. Symptoms stools, symptom relief that ap- two weeks of treatment, as mea- typically improved in as little as proached—but did not quite sured by the Bristol Stool Form seven days but returned after reach—clinical significance, few- (BSF) scale.13 The BSF is a visual ondansetron use stopped (typi- er days with urgency and bloat- scale that depicts stool as hard cally within two weeks). Sixty-five ing, and less frequent defecation. (type 1) to watery (type 7); types 3 percent of patients reported ad- This study did not evaluate the and 4 describe normal stools. The equate relief with ondansetron, long-term effects of ondansetron study also looked at urgency and compared to 14% with placebo. use. However, ondansetron has frequency of defecation, bowel Patients whose diarrhea was been used for other indications transit time, and pain scores. more severe at baseline didn’t re- for more than 25 years and has Treatment with ondansetron spond as well to ondansetron as been reported to have a low risk resulted in a small but statistically did those whose diarrhea was less for adverse effects.15 significant improvement in stool severe. The only frequent adverse consistency. The mean difference effect was constipation, which oc- CHALLENGES in BSF score between ondanse- curred in 9% of patients receiving TO IMPLEMENTATION tron and placebo was –0.9, indi- ondansetron and 2% of those on Remember ondansetron cating slightly more formed stool placebo. is not for IBS patients with constipation Proper use of this drug among Ondansetron should not be patients with IBS is key. The primary benefits of ondansetron are prescribed to IBS patients who experience limited to IBS patients who have ‘‘ diarrhea, and not constipation. constipation or those with mixed Ondansetron should not be pre- symptoms. scribed to IBS patients who experience constipation or those with mixed symptoms. CR with use of ondansetron. Scores WHAT’S NEW for IBS severity—mild’’ (a score of Another option for IBS-D REFERENCES 75 to 175 out of 500), moderate A prior, smaller study of ondanse- 1. Garsed K, Chernova J, Hastings M, et al. A randomised trial of ondansetron for the (175 to 300), or severe (> 300)— tron that used a lower dosage (12 treatment of irritable bowel syndrome with were reduced by more points with mg/d) suggested benefit in IBS- diarrhoea. Gut. 2014;63:1617-1625. ondansetron than with placebo D.14 In that study, ondansetron 2. Hahn BA, Yan S, Strassels S. Impact of irritable bowel syndrome on quality of life and (83 ± 9.8 vs 37 ± 9.7, respectively). decreased diarrhea and function- resource use in the United States and United Although this mean difference al dyspepsia. The study by Garsed Kingdom. Digestion. 1999;60:77-81. of 46 points fell just short of the et al1 is the first large RCT to show 3. Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disor- 50-point threshold that is consid- significantly improved stool con- ders. J Gastrointestin Liver Dis. 2006;15:237- ered clinically significant, many sistency, less frequent defecation, 241. patients exceeded this threshold. and less urgency and bloating 4. Luscombe FA. Health-related quality of life and associated psychosocial factors in irrita- Compared to those who re- from using ondansetron to treat ble bowel syndrome: a review. Qual Life Res. ceived placebo, patients who IBS-D. 2000;9:161-176. took ondansetron also had less 5. Saito YA, Locke GR, Talley NJ, et al. A com- parison of the Rome and Manning criteria for frequent defecation and lower ur- CAVEATS case identification in epidemiological investi- gency scores. Gut transit time was Ondansetron doesn’t appear gations of irritable bowel syndrome. Am J lengthened in the ondansetron to reduce pain Gastroenterol. 2000;95:2816-2824. 1 6. Thompson WG, Heaton KW, Smyth GT, et al. group by 10 hours more than in In Garsed et al, patients who re- Irritable bowel syndrome in general practice: the placebo group. ceived ondansetron did not ex- prevalence, characteristics, and referral. Gut. Pain scores did not change sig- perience relief from pain, which 2000;46:78-82. 7. Tillisch K, Labus JS, Naliboff BD, et al. Char- nificantly for patients taking on- is one of the main complaints of acterization of the alternating bowel habit dansetron, although they experi- IBS. However, this study did find subtype in patients with irritable bowel syn-

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>> continued from page 13 ANSWER The radiograph demonstrates innumerable small lytic defects throughout the calvarium. The patient’s confusion is most likely secondary to profound metabolic abnormalities. However, in the setting of lytic bone lesions, metabolic abnormalities of renal insufficiency, severe hypercalce- mia, and hypomagnesemia, one must be concerned about an oc- cult myeloma, and appropriate work-up must be done. CR

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drome. Am J Gastroenterol. 2005;100:896- Clin Gastroenterol Hepatol. 2008;6:545-555. pregnancy. Expert Opin Drug Saf. 904. 12. Chang L, Chey WD, Harris L, et al. Incidence 2007;6:685-694. 8. Schuster MM. Diagnostic evaluation of the of ischemic colitis and serious complications irritable bowel syndrome. Gastroenterol Clin of constipation among patients using alose- ACKNOWLEDGEMENT North Am. 1991;20:269-278. tron: systematic review of clinical trials and The PURLs Surveillance System was supported in 9. Sandler RS, Everhart JE, Donowitz M, et al. post-marketing surveillance data. Am J Gas- part by Grant Number UL1RR024999 from the The burden of selected digestive diseases in troenterol. 2006;101:1069-1079. National Center For Research Resources, a Clinical the United States. Gastroenterology. 13. Heaton KW, O’Donnell LJ. An office guide to Translational Science Award to the University of 2002;122:1500-1511. whole-gut transit time. Patients’ recollection Chicago. The content is solely the responsibility of 10. Talley NJ. Pharmacologic therapy for the irri- of their stool form. J Clin Gastroenterol. the authors and does not necessarily represent the table bowel syndrome. Am J Gastroenterol. 1994;19:28-30. official views of the National Center For Research 2003;98:750-758. 14. Maxton DG, Morris J, Whorwell PJ. Selective Resources or the National Institutes of Health. 11. Andresen V, Montori VM, Keller J, et al. 5‐hydroxytryptamine antagonism: a role in Copyright © 2014. The Family Physicians Inquiries Effects of 5-hydroxytryptamine (serotonin) irritable bowel syndrome and functional dys- Network. All rights reserved. type 3 antagonists on symptom relief and pepsia? Aliment Pharmacol Ther. constipation in nonconstipated irritable 1996;10:595-599. Reprinted with permission from the Family Physi- bowel syndrome: a systematic review and 15. Gill SK, Einarson A. The safety of drugs for cians Inquiries Network and The Journal of Family meta-analysis of randomized controlled trials. the treatment of nausea and vomiting of Practice. 2014;63(10):600-602.

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