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.

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

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.

The FDA has approved the oral tyrosine kinase inhibitor neratinib (Nerlynx – Puma Biotechnology) for extended adjuvant treatment of adults with early-stage, human epidermal growth factor receptor 2 (HER2)-positive breast cancer, following adjuvant trastuzumab (Herceptin)-based therapy. HER2 is overexpressed in about 20% of breast cancers. Up to 30% of early-stage, HER2-positive breast cancer cases treated with trastuzumab-based adjuvant therapy recur.

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.

The FDA has approved crofelemer (kroe fel’ e mer; Fulyzaq – Salix), a chloride channel inhibitor derived from the red sap of the South American plant Croton lechleri, for symptomatic relief of noninfectious diarrhea in patients with HIV taking antiretroviral drugs. It is the first drug approved for relief of antiretroviral-induced diarrhea and the first oral botanical drug approved by the FDA.

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).

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.

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).

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.

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.

Erlotinib (Tarceva) is the second oral epidermal growth factor receptor (EGFR) inhibitor to become available in the US for treatment of advanced refractory NSCLC. In clinical trials, erlotinib produced a response rate of only 8.9%, but increased median survival from 4.7 to 6.7 months. Patients who had never smoked and those with EGFR-positive tumors survived longer. Erlotinib is generally well tolerated; diarrhea and rash are the most common adverse effects.

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.

Patients planning to travel to other countries often ask physicians for advice about immunizations and prevention of diarrhea and malaria. More detailed advice for travelers is available from the Centers for Disease Control (CDC) at 877-FYI-TRIP (877-394-8747) or www.cdc.gov/travel. Recommendations for the treatment of parasitic diseases are available in the public reading room of The Medical Letter's web site.

Changes caused by one drug in the absorption, distribution, metabolism or excretion of another may lead to a pharmacokinetic adverse drug interaction (DN Juurlink et al, JAMA 2003; 289:1652). Additive drug interactions, such as vasodilation caused by both sildenafil (Viagra) and nitrates, can also have adverse effects.

The FDA recently announced that it will permit reintroduction of alosetron hydrochloride (Lotronex - GlaxoSmithKline) for treatment of irritable bowel syndrome (IBS). The drug was previously withdrawn from the market because of severe gastrointestinal toxicity. The reintroduced drug will have a 50% lower starting dose, a narrower indication and some other marketing restrictions (www.fda.gov/cder/drug/infopage/lotronex/lotronex.htm).

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

Alosetron hydrochloride (Lotronex - Glaxo Welcome), a selective serotonin receptor antagonist, has received FDA approval for treatment of irritable bowel syndrome (IBS) in women whose primary bowel symptom is diarrhea.

Patients planning to travel to other countries often ask pysicians for advice about immunizations and prevention of diarrhea and malaria. Legal requirements for entry and epidemiological conditions in different countries vary from time to time, often unpredictably, but some reasonable recommendations can be made.

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

With the deployment of hundreds of thousands of troops in Saudi Arabia, health problems endemic to the Arabian Peninsula may be coming to the attention of physicians in the USA and other areas.