HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use VIBERZI safely and effectively. See full prescribing information for VIBERZI. VIBERZI (eluxadoline) tablets, for oral use, C-X Initial U.S. Approval: 2015 ---------------------INDICATIONS AND USAGE------------------------ VIBERZI is a mu-opioid receptor agonist, indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D). (1) ------------------DOSAGE AND ADMINISTRATION------------------ • The recommended dosage in adults is 100 mg twice daily taken with food. (2) • The recommended dosage is 75 mg twice daily taken with food in patients who: o do not have a gallbladder (2, 5.1) o are unable to tolerate the 100 mg dose (2, 6.1) o are receiving concomitant OATP1B1 inhibitors (2, 7) o have mild or moderate hepatic impairment (2, 8.6) • Discontinue VIBERZI in patients who develop severe constipation for more than 4 days (2) • If a dose is missed, take the next dose at the regular time; do not take 2 doses at once (2) ----------------DOSAGE FORMS AND STRENGTHS----------------- 75 mg and 100 mg tablets (3) --------------------------CONTRAINDICATIONS------------------------ Patients with:

HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use VIBERZI safely and effectively. See full prescribing information for VIBERZI. VIBERZI (eluxadoline) tablets, for oral use, C-X Initial U.S. Approval: 2015 ---------------------INDICATIONS AND USAGE------------------------ VIBERZI is a mu-opioid receptor agonist, indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D). (1) ------------------DOSAGE AND ADMINISTRATION------------------ • The recommended dosage in adults is 100 mg twice daily taken with food. (2) • The recommended dosage is 75 mg twice daily taken with food in patients who: o do not have a gallbladder (2, 5.1) o are unable to tolerate the 100 mg dose (2, 6.1) o are receiving concomitant OATP1B1 inhibitors (2, 7) o have mild or moderate hepatic impairment (2, 8.6) • Discontinue VIBERZI in patients who develop severe constipation for more than 4 days (2) • If a dose is missed, take the next dose at the regular time; do not take 2 doses at once (2) ----------------DOSAGE FORMS AND STRENGTHS----------------- 75 mg and 100 mg tablets (3) --------------------------CONTRAINDICATIONS------------------------ Patients with:

USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary There are no studies with VIBERZI in pregnant women that inform any drug-associated risks. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. In animal reproduction studies, oral and subcutaneous 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 pre- 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 [see Data]. Data Animal Data Eluxadoline administered as combined oral (1000 mg/kg/day) and subcutaneous (5 mg/kg/day) doses during the period of organogenesis to rats and rabbits (exposures about 51 and 115 times, respectively, the human AUC of 24 ng.h/mL after a single oral dose of 100 mg) did not cause any adverse effects on embryofetal development. A pre- and postnatal development study in rats showed no evidence of any adverse effect on pre- and postnatal development at oral doses of eluxadoline up to 1000 mg/kg/day (with exposures about 10 times the human AUC of 24 ng.h/mL after a single oral dose of 100 mg). In the same study, eluxadoline was detected in the Page 8 of 18 Reference ID: 3766744 milk of lactating rats administered oral doses of 100, 300 and 1000 mg/kg/day (with exposures about 1.8, 3 and 10 times, respectively, the human AUC of 24 ng.h/mL after a single oral dose of 100 mg). Milk samples were collected from six lactating females per group on lactation day 12. Mean concentrations of eluxadoline in the milk of lactating rats on lactation day 12 were 2.78, 5.49 and 44.02 ng/mL at 100, 300 and 1000 mg/kg/day, respectively. 8.2 Lactation Risk Summary No data are available regarding the presence of eluxadoline in human milk, the effects of eluxadoline on the breastfed infant, or the effects of eluxadoline on milk production. However, eluxadoline is present in rat milk [see Use in Specific Populations (8.1) ]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VIBERZI and any potential adverse effects on the breastfed infant from VIBERZI or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Juvenile Toxicology Data Eluxadoline was orally administered to juvenile rats at 500, 750, and 1500 mg/kg/day (about 16, 54 and 30 times, respectively, the human AUC of 24 ng.h/mL after a single oral dose of 100 mg) for 4 weeks. There were no adverse physiologic effects related to eluxadoline. Based on these results, the NOAEL for male and female juvenile rats was 1500 mg/kg/day (about 30 times the human AUC of 24 ng.h/mL after a single oral dose of 100 mg). 8.5 Geriatric Use Of 1795 IBS-D patients in clinical trials of VIBERZI who received 75 mg or 100 mg twice daily, 139 (7.7%) were at least 65 years of age, while 15 (0.8%) were at least 75 years old. No overall differences in effectiveness were observed between these patients and younger patients. There were no overall differences in the types of adverse reactions observed between elderly and younger patients; however, a higher proportion of elderly patients than younger patients experienced adverse reactions (66% vs 59%), serious adverse reactions (9% vs 4%), and gastrointestinal adverse reactions (39% vs 28%). 8.6 Hepatic Impairment Plasma concentrations of eluxadoline increase in patients with hepatic impairment [see Clinical Pharmacology (12.3)]. Page 9 of 18 Reference ID: 3766744 VIBERZI is contraindicated in patients with severe hepatic impairment (Child-Pugh Class C) as plasma concentrations of eluxadoline increase significantly (16-fold) and there is no information to support the safety of VIBERZI in these patients. In patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment, plasma concentrations of eluxadoline increase to a lesser extent (4- and 6-fold, respectively). Administer VIBERZI at a reduced dose of 75 mg twice daily to these patients [see Dosage and Administration (2)]. Monitor patients with any degree of hepatic impairment for impaired mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery and for other eluxadoline-related adverse reactions [see Adverse Reactions (6.1)]. 9 9.1 Pending 9.2 DRUG ABUSE AND DEPENDENCE Controlled Substance Abuse In a drug discri