ELUXADOLINE Drug Interactions: What You Need to Know

INTERACTIONS Tables 2 and 3 include drugs which demonstrated a clinically important drug interaction with VIBERZI or which potentially may result in clinically relevant interactions.

Table

2: Established and Other Potentially Clinically Relevant Interactions Affecting VIBERZI OATP1B1 Inhibitors Clinical Impact: Increased exposure to eluxadoline when coadministered with cyclosporine [ see Clinical Pharmacology ( 12.3 ) ] Intervention: Administer VIBERZI at a dose of 75 mg twice daily [see Dosage and Administration ( 2 )] and monitor patients 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 )] . Examples: cyclosporine, gemfibrozil, antiretrovirals (atazanavir, lopinavir, ritonavir, saquinavir, tipranavir), rifampin, eltrombopag Drugs that Cause Constipation Clinical Impact: Increased risk for constipation related adverse reactions and potential for constipation related serious adverse reactions Intervention: Avoid use with other drugs that may cause constipation (see below); loperamide may be used occasionally for acute management of severe diarrhea but avoid chronic use. Discontinue loperamide immediately if constipation occurs. Examples: alosetron, anticholinergics, opioids Table 3: Established and Other Potentially Clinically Relevant Interactions Affecting Drugs Co-Administered with VIBERZI OATP1B1 and BCRP Substrate Clinical Impact: VIBERZI may increase the exposure of co-administered OATP1B1 and BCRP substrates. Increased exposure to rosuvastatin when co-administered with VIBERZI with a potential for increased risk of myopathy/rhabdomyolysis [ see Clinical Pharmacology ( 12.3 ) ] Intervention: Use the lowest effective dose of rosuvastatin (see prescribing information of rosuvastatin for additional information on recommended dosing). See full prescribing information for clinically relevant interactions. ( 7 )

VIBERZI is contraindicated in patients: Without a gallbladder. These patients are at increased risk of developing serious adverse reactions of pancreatitis and/or sphincter of Oddi spasm [see Warnings and Precautions ( 5.1 , 5.2 )] With known or suspected biliary duct obstruction; or sphincter of Oddi disease or dysfunction. These patients are at increased risk for sphincter of Oddi spasm [see Warnings and Precautions ( 5.1 )]. With alcoholism, alcohol abuse or alcohol addiction, or in patients who drink more than 3 alcoholic beverages per day. These patients are at increased risk for acute pancreatitis [see Warnings and Precautions ( 5.1 )]. With a history of pancreatitis; or structural diseases of the pancreas, including known or suspected pancreatic duct obstruction. These patients are at increased risk for acute pancreatitis [see Warnings and Precautions ( 5.1 )] . With a known hypersensitivity reaction to VIBERZI [see Warnings and Precautions ( 5.3 )]. With severe hepatic impairment (Child-Pugh Class C). These patients are at risk for significantly increased plasma concentrations of eluxadoline [see Use in Specific Populations ( 8.6 )] With a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction. These patients may be at risk for severe complications of bowel obstruction [see Warnings and Precautions ( 5.4 )] . patients without a gallbladder ( 4 ) known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction ( 4 ) alcoholism, alcohol abuse, alcohol addiction, or drink more than 3 alcoholic beverages/day ( 4 ) a history of pancreatitis; structural diseases of the pancreas, including known or suspected pancreatic duct obstruction ( 4 ) patients with a known hypersensitivity reaction to VIBERZI ( 4 , 5.3 ) severe hepatic impairment (Child-Pugh Class C) ( 4 , 8.6 ) a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction ( 4 )

AND PRECAUTIONS Pancreatitis and Sphincter of Oddi Spasm : Monitor patients for new or worsening abdominal pain, with or without nausea and vomiting, or acute biliary pain with liver or pancreatic enzyme elevations; immediately discontinue VIBERZI and seek medical attention if symptoms develop. ( 5.1 , 5.2 )

Hypersensitivity

Reactions, including anaphylaxis : Immediately discontinue VIBERZI and seek medical attention if symptoms develop. ( 4 , 5.3 ) Constipation: Instruct patients to stop VIBERZI and immediately contact their healthcare provider if they develop severe constipation. Avoid use with other drugs that may cause constipation ( 5.4 , 7 )

5.1 Pancreatitis Pancreatitis, with or without sphincter of Oddi spasm [ see Warnings and Precautions ( 5.1 ) ] , has been reported in patients taking either the 75 mg or 100 mg dosage of VIBERZI, including serious cases resulting in hospitalization, primarily in patients without a gallbladder. Fatal cases have also been reported in patients without a gallbladder. VIBERZI is contraindicated in patients without a gallbladder [ see Contraindications ( 4 ) ] . Most of the reported cases of serious pancreatitis occurred within a week of starting treatment with VIBERZI and some developed symptoms after one to two doses. In patients with a gallbladder, evaluate a patient’s alcohol intake prior to starting VIBERZI. Instruct patients to avoid chronic or acute excessive alcohol use while taking VIBERZI. Monitor for new or worsening abdominal pain that may radiate to the back or shoulder, with or without nausea and vomiting. Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of pancreatitis such as acute abdominal or epigastric pain radiating to the back or shoulder associated with elevations of pancreatic enzymes with or without nausea and vomiting [ see Contraindications ( 4 ) ] .

5.2 Sphincter of Oddi Spasm There is a risk of sphincter of Oddi spasm, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain (e.g., biliary-type pain) in patients taking VIBERZI [ see Adverse Reactions ( 6.1 ) ] . Postmarketing serious adverse reactions of sphincter of Oddi spasm with or without pancreatitis resulting in hospitalization have been reported, primarily in patients without a gallbladder [ see Warnings and Precautions ( 5.1 ) ] . Most of the reported cases of serious sphincter of Oddi spasm occurred within a week of starting treatment with VIBERZI and some developed symptoms after one to two doses. VIBERZI is contraindicated in patients without a gallbladder [ see Contraindications ( 4 ) ] . Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of sphincter of Oddi spasm such as acute worsening of abdominal pain, (e.g. acute epigastric or biliary [i.e., right upper quadrant] pain), that may radiate to the back or shoulder with or without nausea and vomiting, associated with elevations of pancreatic enzymes or liver transaminases. Do not restart VIBERZI in patients who developed biliary duct obstruction or sphincter of Oddi spasm while taking VIBERZI [ see Contraindications ( 4 ) ] .

5.3 Hypersensitivity Reactions In postmarketing experience, serious hypersensitivity reactions (including anaphylaxis) have been reported following VIBERZI administration. Some of these reactions occurred after the first one or two doses of VIBERZI [ see Adverse Reactions ( 6.2 )] . Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of a hypersensitivity reaction [ see Contraindications ( 4 ) ] .

5.4 Constipation Constipation, sometimes requiring hospitalization, has been reported following VIBERZI administration. In postmarketing experience, severe cases with development of intestinal obstruction, intestinal perforation, and fecal impaction, requiring intervention, have also been reported. Instruct patients to stop VIBERZI and immediately contact their healthcare provider if they experience severe constipation. Avoid use with other drugs that may cause constipation [ see Adverse Reactions ( 6.1 ), Drug Interactions ( 7 ) ] .