Irritable bowel syndrome (IBS) is considered to be one of the most commonly encountered gastrointestinal (GI) disorders around the world. About 20 percent of people in developed countries will have IBS symptoms during some point in their lives.

IBS is known to affect the GI tract, particularly the colon, and the diagnosis can arise from other problems such as inflammatory bowel disease, celiac disease, cancer or malabsorption. The characteristic traits of IBS can include intermittent abdominal pain/discomfort, altered bowel habits and abdominal bloating/distention.

There are three current medications that are typically reserved for moderate to severe IBS in patients who have not achieved relief with other interventions. These medications are linaclotide (Linzess), eluxadoline (Viberzi), rifaximin (Xifaxin), which are all used for IBS with constipation or with diarrhea.

Let's take a closer look at these three prescriptions.


Linaclotide (Linzess) is a gastrointestinal agent that is FDA-approved for IBS with constipation. It binds and agonizes guanylate cyclase-C on the luminal surface of intestinal epithelium.

Intracellular and extracellular cyclic guanosine monophosphate (cGMP) concentrations are increased, which can result in chloride and bicarbonate being secreted into the intestinal lumen. Intestinal fluid increases and GI transit time is decreased and increased extracellular cGMP may decrease visceral pain by reducing pain-sensing nerve activity.

The FDA approval of linaclotide came in 2012 based off its safety and effectiveness being established in two double-blind studies. A total of 1,272 patients were randomly assigned to either take linaclotide 145mcg, 290mcg or placebo for 12 weeks. At the end of the study, the patients who took linaclotide experienced more complete spontaneous bowel movements compared to those who took placebo.

The approval of linaclotide also came with a boxed warning that indicated it is contraindicated in pediatric patients under 6 years of age and to avoid use in patients 6 to 17 years of age due to death from dehydrating being observed in young juvenile animals during nonclinical studies.


Eluxadoline (Viberzi) is another gastrointestinal agent that is FDA-approved for IBS with diarrhea. Eluxodoline is a mixed mu-opiouid receptor agonist, delta opioid receptor antagonist, and kappa opioid receptor agonist that acts by reducing abdominal pain and diarrhea in patients with IBS with diarrhea without the development of constipating side effects.

The approval of eluxadoline was based off its safety and efficacy being established in two double-blind, placebo-controlled clinical trials. The trials consisted of 2,425 patients who were assigned to receive eluxadoline or placebo.

The results of the trials demonstrated greater effectiveness for eluxadoline with the reduction of abdominal pain and improvement of stool consistency when compared to placebo during the 26-week treatment period. The common side effects that are observed include nausea, constipation and abdominal pain, with more serious effects including the risk of spasm in the sphincter of Oddi.


Lastly, rifaximin (Xifaxan) is an antibiotic that is FDA-approved for IBS with diarrhea. It works by inhibiting bacterial RNA synthesis and binding to bacterial DNA-dependent RNA polymerase.

The approval of rifaximin came from its safety and efficacy being established in three double-blind, placebo-controlled trials. The first two trials consisted of 1,258 patients who were randomly assigned to either receive rifaximin or placebo for 14 days followed by a 10-week treatment free phase. The two trials showed improvement in abdominal pain and stool consistency with rifaximin compared to placebo.

The third trial analyzed repeat courses of rifaximin, in which a total of 636 patients with recurrent IBS-D were randomized to receive rifaximin or placebo for two additional 14-day courses that were spaced out by 10 weeks. The results of the trial showed that participants on rifaximin achieved a response with rifaximin for abdominal pain and stool consistency compared to placebo.

For individuals diagnosed with IBS, the condition can present daily challenges due to the presenting symptoms that can impact their quality of life. The advent of both nonpharmacological and pharmacological interventions can help individuals to cope more easily and achieve symptom management.