Eluxadoline (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ELUXADOLINE
- VIBERZI
Indications and Usage
VIBERZI is indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D).
Dosage and Administration
The recommended dosage of VIBERZI is 100 mg taken orally twice daily with food. The recommended dosage of VIBERZI is 75 mg taken orally twice daily with food in patients: unable to tolerate the 100 mg dose of VIBERZI [see Adverse Reactions ( 6.1 ) ]. receiving concomitant OATP1B1 inhibitors [see Drug Interactions ( 7 )] . with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment [see Use in Specific Population s ( 8.6 ) ] . with moderate or severe renal impairment (eGFR less than 60 mL/min/1.73 m2); and in patients with end stage renal disease (ESRD) not yet on dialysis (eGFR less than 15 mL/min/1.73 m2) [see Use in Specific Populations ( 8.7 )]. Discontinue VIBERZI in patients who develop severe constipation [see Warnings and Precautions ( 5.4 )] . Instruct patients if they miss a dose, take the next dose at the regular time and not to take 2 doses at the same time to make up for a missed dose.
Contraindications
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 )] .
Adverse Reactions
The following adverse reactions described below and elsewhere in the labeling include: Pancreatitis [see Warnings and Precautions ( 5.1 )] Sphincter of Oddi Spasm [ see Warnings and Precautions ( 5.2 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Constipation [see Warnings and Precautions ( 5.4 )]
Drug 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).
Mechanism of Action
Eluxadoline is a mu-opioid receptor agonist; eluxadoline is also a delta opioid receptor antagonist and a kappa opioid receptor agonist. The binding affinities (Ki) of eluxadoline for the human mu and delta opioid receptors are 1.8 nM and 430 nM, respectively. The binding affinity (Ki) of eluxadoline for the human kappa opioid receptor has not been determined; however, the Ki for guinea pig cerebellum kappa opioid receptor is 55 nM. In animals, eluxadoline interacts with opioid receptors in the gut.
Overdosage
No reports of overdosage with VIBERZI have been reported. In the event of acute overdose, the stomach should be emptied and adequate hydration maintained. The patient should be carefully observed and given standard supportive treatment as required. Given eluxadoline’s action at opioid receptors, administration of a narcotic mu-opioid antagonist, such as naloxone, should be considered. Considering the short half-life of naloxone, repeated administration may be necessary. In the event of naloxone administration, subjects should be monitored closely for the return of overdose symptoms, which may indicate need for repeated naloxone injection.