Clostridioides (formerly Clostridium) difficile infection (CDI) is the most common infectious cause of healthcare-associated diarrhea in adults. Guidelines on management of CDI have recently been updated.

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain and altered bowel habits, often accompanied by bloating.IBS is classified according to the predominant bowel symptom as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), or unclassified (IBS-U). Alterations in the microbiome, stress responses, sensory and motor function of the gut, and host genetic factors may be contributing factors. Since the exact cause of IBS is unknown, the goal of treatment is symptom control.

View the Table: Safety of Drugs for IBS in Pregnancy and Lactation

Patients who receive pretravel advice can reduce their risk for many travel-related conditions. Vaccines recommended for travelers are reviewed in a separate issue.

View the Expanded Table: Antibiotics for Travelers' Diarrhea

The FDA has approved rifamycin (Aemcolo – Cosmo/ Aries), a minimally absorbed oral antibiotic, for treatment of adults with travelers' diarrhea (TD) caused by noninvasive strains of Escherichia coli. It is not recommended for treatment of diarrhea that is complicated by fever and/or bloody stools. Topical and injectable formulations of rifamycin have been used in Europe for other indications for many years.

View Table: Drugs for Ulcerative Colitis

View Table: Drugs for Crohn's Disease

The FDA has warned that eluxadoline (Viberzi – Allergan), a mu-opioid receptor agonist and delta-opioid receptor antagonist approved in 2015 for treatment of irritable bowel syndrome with diarrhea (IBS-D),1 should not be used in patients without a gallbladder because of an increased risk of serious pancreatitis.2

As of February 2017, the FDA had received reports of 118 cases of serious, nonfatal pancreatitis and 2 deaths associated with use of eluxadoline. Both deaths occurred in patients without a gallbladder who developed severe abdominal pain and vomiting shortly after taking the first dose. At least 48 of the cases occurred after only 1 or 2 doses of eluxadoline. Of the 68 patients whose gallbladder status was reported, 56 did not have a gallbladder. Most of the patients without a gallbladder (44/56) were taking the reduced dosage of eluxadoline recommended for such patients (75 mg once/day).

Patients considered at risk for pancreatitis were excluded from the two trials that led to approval of eluxadoline. One case of pancreatitis and 8 cases of abdominal pain with hepatic enzyme elevation associated with sphincter of Oddi spasm occurred with use of eluxadoline in the trials, all in patients without a gallbladder.3

According to the current label, eluxadoline is contraindicated in patients who abuse alcohol (including those who consume >3 servings of alcohol per day) and in those with known or suspected biliary duct, pancreatic duct, or GI tract obstruction, sphincter of Oddi disease or dysfunction, or severe hepatic impairment (Child-Pugh C). It is also contraindicated in those with a history of pancreatitis, structural pancreatic disease, or chronic or severe constipation.

Some alternatives to eluxadoline, which is only modestly more effective than placebo in relieving IBS-D symptoms, are the antidiarrheal loperamide (Imodium, and generics), the non-absorbed antibiotic rifaximin (Xifaxan), and the 5-HT₃ receptor antagonist alosetron (Lotronex, and generics). Taken as needed, loperamide can reduce postprandial urgency and stool frequency, but it does not improve global symptoms of IBS-D. Like eluxadoline, rifaximin has only been modestly effective in relieving symptoms. Because of concerns about severe constipation and ischemic colitis, alosetron should be used only in women with severe, chronic IBS-D that is unresponsive to other drugs.4

1. Eluxadoline (Viberzi) for irritable bowel syndrome with diarrhea. Med Lett Drugs Ther 2016; 58:4.
2. FDA Drug Safety Communication: FDA warns about increased risk of serious pancreatitis with irritable bowel drug Viberzi (eluxadoline) in patients without a gallbladder. Available at: www.fda.gov. Accessed April 13, 2017.
3. AJ Lembo et al. Eluxadoline for irritable bowel syndrome with diarrhea. N Engl J Med 2016; 374:242.
4. Drugs for irritable bowel syndrome. Med Lett Drugs Ther 2016; 58:121.

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Irritable bowel syndrome (IBS) is a common disorder characterized by chronic, intermittent abdominal pain or discomfort and altered bowel habits. It is subtyped according to the predominant bowel symptom as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), or unclassified (IBS-U). Since the exact cause of IBS is unknown, the goal of treatment is symptom control.

The FDA has approved eluxadoline (Viberzi – Actavis), a mu-opioid receptor agonist and delta-opioid receptor antagonist, for oral treatment of adults with irritable bowel syndrome with diarrhea (IBS-D).

Rifaximin (Xifaxan – Salix), a minimally absorbed oral antibiotic approved previously to treat travelers' diarrhea and to reduce the risk of recurrent hepatic encephalopathy, has now been approved by the FDA for treatment of irritable bowel syndrome with diarrhea (IBS-D). Eluxadoline (Viberzi – Actavis), a mu-opioid receptor agonist, was also recently approved for IBS-D and will be reviewed in a future issue.

Patients planning to travel to other countries often ask for information about prevention of diarrhea, malaria, and other travel-related conditions. Vaccines recommended for travelers based on their destination, length of stay, and planned activities were reviewed in a previous issue.

Aminosalicylates are effective for induction and maintenance of remission in mild to moderate ulcerative colitis. They are not recommended for treatment of Crohn's disease.

FORMULATIONS — Oral mesalamine is rapidly absorbed in the small intestine and most of the drug does not reach the colon. Pentasa releases mesalamine gradually throughout the gastrointestinal tract. Delzicol, Asacol HD, Lialda, and Apriso delay the release of the drug until it reaches the distal ileum and colon. Sulfasalazine (Azulfidine, and generics), balsalazide (Colazal, and others), and olsalazine (Dipentum) are prodrugs; mesalamine is azo-bonded to a second moiety and released in the colon following bacterial cleavage of the bond. Mesalamine is also available as an enema (Rowasa, and generics) and as a rectal suppository (Canasa).

Patients planning to travel to other countries often ask for information about appropriate vaccines and prevention of diarrhea and malaria. More detailed advice for travelers is available from the Centers for Disease Control and Prevention (CDC) at www.cdc.gov/travel. Guidelines are also available from the Infectious Diseases Society of America (IDSA).

Inflammatory bowel disease (IBD) is generally classified as either Crohn’s disease (CD) or ulcerative colitis (UC). More detailed guidelines on their treatment are available from the American College of Gastroenterology.

Irritable bowel syndrome (IBS) is a common disorder, occurring in up to 15% of the US population; it is 2-2.5 times more frequent in women than in men. IBS is characterized by chronic, intermittent abdominal pain or discomfort accompanied by altered bowel habits. Since the underlying mechanisms of disease remain unclear, management of IBS focuses on symptom control.

Clostridium difficile infection (CDI) is the most common infectious cause of healthcare-associated diarrhea in adults. The incidence and severity of CDI have increased in recent years with the emergence of an epidemic virulent strain (NAP1/BI/027). Common risk factors include admission to a healthcare facility, increasing age and severity of underlying illness, gastric acid suppression and exposure to antimicrobials, particularly clindamycin, ampicillin, cephalosporins or fluoroquinolones. Patients who develop CDI while receiving a precipitating antibiotic should have the antibiotic discontinued, if possible, or switched to another appropriate antimicrobial with a lower risk of CDI.

The FDA has approved a new 550-mg tablet of rifaximin (Xifaxan – Salix), a minimally absorbed oral antibiotic, to reduce the risk of recurrent hepatic encephalopathy (HE). A 200-mg tablet has been available for treatment of travelers’ diarrhea since 2004.

Patients planning to travel to other countries often ask physicians for information about appropriate vaccines and prevention of diarrhea and malaria. Guidelines are also available from the Infectious Diseases Society of America (IDSA).

Inflammatory bowel disease (IBD) is either Crohn's disease or ulcerative colitis. Drug selection is guided by disease type (Crohn's versus ulcerative colitis), severity and location and whether the goal is induction or maintenance of remission. Table 1 on page 66 lists the drugs used to treat IBD with their formulations and cost. Table 2 on page 68 lists the drugs of choice and their doses for different indications. Table 3 on page 71 lists the drugs' adverse effects and recommendations for monitoring. More detailed guidelines are available from the American College of Gastroenterology.

The most common cause of travelers' diarrhea, usually a self-limited illness without fever lasting several days, is infection with noninvasive enterotoxigenic (ETEC) or enteroaggregative (EAEC) strains of Escherichia coli. Campylobacter, Shigella, Salmonella, Aeromonas, viruses and parasites are less common.

The gram-positive anaerobic bacillus Clostridium difficile is the most common identifiable cause of antibiotic-associated diarrhea. The antibiotics most often implicated have been ampicillin, second and third generation cephalosporins, clindamycin and fluoroquinolones. The emergence in recent years of a new, more toxic epidemic strain (BI/NAP1), possibly related to widespread use of fluoroquinolones, has caused a marked increase in the incidence and severity of C. difficile-associated disease (CDAD).

Patients planning to travel to other countries often ask physicians for information about immunizations and prevention of diarrhea and malaria. More detailed advice for travelers is available from the Centers for Disease Control and Prevention at 877-FYI-TRIP (877-394-8747) or www.cdc.gov/travel.

Irritable bowel syndrome (IBS) is a common disorder, occuring in about 15% of the US population; it is 2-3 times more frequent in women than in men. IBS is characterized by chronic abdominal pain or discomfort and altered bowel habits.

Rifaximin (Xifaxan - Salix), a non-absorbed oral antibiotic derived from rifampin (Rifadin, and others), has been approved by the FDA for treatment of travelers' diarrhea caused by noninvasive strains of Escherichia coli in patients 12 years of age or older. It has been available in Europe since 1987.