Eluxan 100

Indicated for diarrhea-predominant, irritable bowel syndrome (IBS-D), in adult men and women

May be taken with food.

Irritable Bowel Syndrome Indicated for diarrhea-predominant irritable bowel syndrome (IBS-D) in adult men and women 100 mg PO BID with food Discontinue in patients who develop severe constipation lasting >4 days Hepatic impairment Mild-to-moderate (Child-Pugh A or B): Decrease dose to 75 mg PO BID; monitor for impaired mental or physical abilities needed to perform potentially hazardous activities Severe (Child-Pugh C): Contraindicated

Documented hypersensitivity to drug or components of the formulation Patients who do not have a gallbladder Known or suspected gallbladder obstruction, biliary duct obstruction or sphincter of Oddi disease or dysfunction; increased risk for sphincter of Oddi spasm Alcoholism, alcohol abuse, alcohol addiction, or in patients who drink >3 alcoholic beverages/day; increased risk of pancreatitis History of pancreatitis, pancreatic duct obstruction, or structural diseases of the pancreas; increased risk of acute pancreatitis Severe hepatic impairment (Child-Pugh C); risk of significantly increased eluxadoline plasma concentrations

Mu opioid receptor agonist; it also is a delta opioid receptor antagonist and a kappa opioid receptor agonist The multiple opioid activity is designed to treat the symptoms of IBS-D while reducing the incidence of constipation that can occur with unopposed mu opioid receptor agonists

Eluxadoline is a mu opioid receptor agonist; because of this mechanism of action, the potential for increased risk of sphincter of Oddi spasm exists, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain In patients with a gallbladder, evaluate a patient’s alcohol intake prior to starting therapy; instruct patients to avoid chronic or acute excessive alcohol use while in therapy; monitor for new or worsening abdominal pain that may radiate to back or shoulder, with or without nausea and vomiting; instruct patients to immediately stop therapy and seek medical attention if they experience symptoms suggestive of pancreatitis such as acute abdominal or epigastric pain radiating to back or shoulder associated with elevations of pancreatic enzymes with or without nausea and vomiting Lactation Unknown if distributed in human breast milk Secreted in rat milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

1-10% Constipation (7-8%) Nausea (7-8%) Abdominal pain (6-7%) URT infection (3-5%) Vomiting (4%) Nasopharyngitis (3-4%) Abdominal distention (3%) Bronchitis (3%) Dizziness (3%) Flatulence (3%) Rash (3%) Increased ALT (2-3%) Fatigue (2-3%) Viral gastroenteritis (1-3%) <2% Gastrointestinal: GERD General disorders: Feeling drunk Investigations: Increased AST Nervous system: Sedation, somnolence Psychiatric disorders: Euphoric mood Respiratory: Asthma, bronchospasm, respiratory failure, wheezing <1% Severe constipation

Pregnancy No studies in pregnant women Animal reproduction studies Oral and SC administration of eluxadoline to rats and rabbits during organogenesis at doses approximately 51 and 115 times the human exposure after a single oral dose of 100 mg, respectively, demonstrated no teratogenic effects. In a prenatal and postnatal development study in rats No adverse effects were observed in offspring with oral administration of eluxadoline at doses approximately 10 times the human exposure Lactation Unknown if distributed in human breast milk Secreted in rat milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition