Serotonin (5-HT3) receptor antagonist (IBS-D) Alosetron (Lotronex): should not be used in women with severe diarrhea, potentially severe adverse effects Ondansetron (Zofran): 4 mg up to 4 times daily; has similar but less robust benefit as alosetron but with an excellent safety profile (Table 5) Serotonin (5-HT4) receptor agonist (IBS-C) Tegaserod (Zelnorm): 6 mg twice daily for adult women younger than 65 years with IBS-C; contraindicated if more than 1 cardiac risk factor; small concern about excess cardiovascular ischemic events Prosecretory agents (IBS-C) Linaclotide (Linzess): 72 mcg daily or 145 mcg daily (for chronic constipation), 290 mcg daily for IBS-C; guanylate cyclase C receptor agonist that induces chloride secretion in the gut and results in looser stools, increased colonic transit, and decreased pain compared with placebo Lubiprostone (Amitiza): 8 mcg twice daily for women with IBS-C, 24 mcg twice daily for men and women with chronic constipation; prostaglandin derivative that induces chloride secretion in the gut and results in looser stools and increased colonic transit and decreased pain compared with placebo; occasional mild nausea occurs Plecanatide (Trulance): 3 mg or 6 mg daily for IBS-C and chronic constipation; analogue of an endogenous guanylate cyclase C receptor agonist that induces chloride secretion in the gut and results in looser stools and increased colonic transit compared with placebo; dose can be titrated to minimize diarrhea Nonabsorbable antibiotics (IBS-D) Rifaximin (Xifaxan): 550 mg by mouth 3 times daily for 14 days; recurrent symptoms can be treated up to 3 times, with 3 months between treatments; improves diarrhea, urgency, bloating, and pain compared with placebo; may act by improving small intestinal bacterial overgrowth No evidence of adverse effects and no increased risk of Clostridioides difficile infection Stimulant laxatives (opioid-induced constipation) Stimulant laxatives (bisacodyl [Dulcolax], cascara, senna) increase motility in chronic constipation but may cause pain and diarrhea; usually reserved for patients with dysmotility disorders or opioid-induced constipation Opioid receptor agonists (IBS-D) Eluxadoline (Viberzi): 100 mg twice daily (75 mg twice daily if higher dose is not tolerated or if the patient has hepatic impairment); novel action on opioid receptors in the gut, relieves diarrhea and pain in IBS-D May cause nausea and headache, and rarely pancreatitis and sphincter of Oddi spasm; contraindicated in patients with history of biliary obstruction, cholecystectomy, pancreatitis, severe hepatic impairment, and in those who drink more than 3 alcoholic beverages per day