13/15. Vibella- (Deoxycholic acid)- (Apr 2015)- to treat irritable bowel syndrome with diarrhoea (IBS-D)- in adult men and women

Name of the Drug-   VIBELLA

Active Ingredient-       Deoxycholic acid

Indication-                  To treat irritable bowel syndrome with Diarrhoea(IBS-D) inadult men                                       and women

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).

ADVERSE REACTIONS-

 Most common adverse reactions (>5%) are constipation, nausea and abdominal pain.

CONTRAINDICATIONS-

 Patients with: • known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction (alcoholism, alcohol abuse, alcohol addiction, or drink more than 3 alcoholic beverages/day 

• a history of pancreatitis; structural diseases of the pancreas, including known or suspected pancreatic duct obstruction

 • severe hepatic impairment (Child-Pugh Class C)

 • severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction 

WARNINGS AND PRECAUTIONS-

 • Sphincter of Oddi Spasm and Pancreatitis: Monitor patients without a gallbladder for new or worsening abdominal pain, with or without nausea and vomiting, or acute biliary pain with liver or pancreatic enzyme elevations; discontinue VIBERZI and seek medical attention if symptoms develop.

DOSAGE AND ADMINISTRATION-

 • The recommended dosage in adults is 100 mg twice daily taken with food.

 • The recommended dosage is 75 mg twice daily taken with food in patients who: o do not have a gallbladder 

o are unable to tolerate the 100 mg dose

 o are receiving concomitant OATP1B1 inhibitors

 o have mild or moderate hepatic impairment 

• Discontinue VIBERZI in patients who develop severe constipation for more than 4 days

 • If a dose is missed, take the next dose at the regular time; do not take 2 doses at once 

-DOSAGE FORMS AND STRENGTHS-

75 mg and 100 mg tablets 

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Instruct patients to:

• stop VIBERZI and seek medical attention if unusual or severe abdominal pain develops, especially if they do not have a gallbladder

• avoid chronic or acute excessive alcohol use while taking VIBERZI

• take one tablet twice daily with food.

• if they miss a dose, take the next dose at the regular time. Do not take 2 doses at the same time to make up for a missed dose.

• call their healthcare provider if they are unable to tolerate VIBERZI

• discontinue VIBERZI and call their health care provider if they experience constipation lasting more than 4 days

• not take alosetron with VIBERZI or not take loperamide on a chronic basis with VIBERZI due to the potential for constipation. Loperamide may occasionally be used with VIBERZI for acute management of severe diarrhea, but must be discontinued if constipation develops.

Also, instruct patients to avoid taking VIBERZI with other medications that may cause constipation (for example opioids, anticholinergics, etc.).

Manufactured by: Patheon Pharmaceuticals, Inc Cincinnati, OH 45237-1625 USA Distributed by: Forest Pharmaceuticals, Inc. Subsidiary of Forest Laboratories, LLC Cincinnati, Ohio 45209 USA © 2015 Actavis. All rights reserved.

CLINICAL PHARMACOLOGY

1. Mechanism of Action

Eluxadoline is a mu-opioid receptor agonist; eluxadoline is also a delta opioid receptor antagonist and a kappa opioid receptor agonist.

2. Pharmacodynamics Cardiac Electrophysiology At a dose 10 times the maximum recommended dose (100 mg), VIBERZI does not prolong the QT interval to any clinically relevant extent.

Absorption Absolute bioavailability of eluxadoline has not been determined. The median Tmax value was 1.5 hours (range: 1 to 8 hours) under fed conditions and 2 hours (range: 0.5 to 6 hours) under fasting conditions.

The administration of VIBERZI with a high fat meal that contained approximately 800 to 1000 total calories, with 50% of calories being derived from fat content decreased the Cmax of eluxadoline by 50% and AUC by 60%.

Distribution-

Plasma protein binding of eluxadoline was 81%. Page 12 of 18 Reference ID: 3766744

Elimination The mean plasma elimination half-life of eluxadoline ranged from 3.7 hours to 6 hours.

Metabolism Metabolism of eluxadoline is not clearly established [see Drug Interactions (7)]. There is evidence that glucuronidation can occur to form an acyl glucuronide metabolite.

Excretion-  82.2% of the total radioactivity was recovered in feces within 336 hours and less than 1% was recovered in urine within 192 hours.

Specific Populations Hepatic Impairment Following a single oral 100–mg dose in subjects with varying degrees of liver impairment and healthy subjects, mean eluxadoline plasma exposure was 6-fold, 4-fold, and 16-fold higher in mild, moderate, and severe hepatically impaired subjects (Child Pugh Class A, B, C), respectively, compared to the subjects with normal liver function [see Dosage and Administration (2), Contraindications (4), Use in Specific Populations (8.6

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.

2 Lactation Risk Summary-

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.

3.Pediatric Use Safety and effectiveness in pediatric patients have not been established. 

4. 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.

5 Hepatic Impairment- Plasma concentrations of eluxadoline increase in patients with hepatic impairment.

6. DRUG ABUSE AND DEPENDENCE-

Controlled Substance Abuse In a drug discrimination study in monkeys, intravenous administration of eluxadoline hydrochloride produced full generalization to the morphine cue. In a self-administration study in monkeys, eluxadoline hydrochloride was self-administered to a degree that was less than that of heroin but greater than that of saline.

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.