Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.

Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT₃ antagonist, works by slowing the movement of stools in the gut, reducing bowel contractions, and blocking signals to the brain that trigger the feeling of pain. It is initially given at a dose of 0.5 mg daily, which can be increased to a maximum of 1 mg twice daily if necessary. It may cause serious side effects such as constipation, ischemic colitis, nausea, vomiting, GI discomfort and pain, diarrhea, flatulence, and hemorrhoids. Due to the fatal consequences of ischemic colitis, it was initially withdrawn from the US market. Later, it was reintroduced, with its use being restricted to severe cases of IBS-D in women who have not responded to conventional therapies. It also requires a prescription program with physician certification, patient education, and consent protocol before dispensing.

Eluxadoline, on the other hand, is an opioid receptor agonist and antagonist. It is used for treating adults with IBS-D and acts locally in the gut to reduce abdominal pain and diarrhea without triggering constipation. Its low oral bioavailability limits its potential for adverse effects on the central nervous system's opioid receptors. Other side effects include constipation, nausea, and abdominal pain. Eluxadoline is dosed at 100 mg twice daily with food in patients with a gallbladder and 75 mg twice daily in patients without a gallbladder. Furthermore, it is prohibited in patients with biliary duct obstruction, sphincter or Oddi disease or dysfunction, or a history of pancreatitis.