Brand Information

Strength	Rate	Packing Style
mg	0.00	unit

Drug Interaction:

The metabolism of eluxadoline by CYP pathways has not been clearly established.

In addition, the potential of eluxadoline to inhibit CYP3A4 in the gut has not been

established

Indication:

VIBERZI (eluxadoline) tablets, for oral use, C-X

Initial U.S. Approval: 2015

Proprietary Name- VIBERZI

Established Name- Eluxadoline

Applicant- Furiex Pharmaceuticals Inc.

Indication- For the treatment of Irritable Bowel Syndrome with Diarrhea

Approval Date- 5/27/2015

Approved by U.S.FDA on 30-06-2015 (Ref- FDA approved List- 2015)

NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL

PRODUCTS APPROVED FOR 2015

Certain drugs are classified as New molecular Emtities- NME- for FDA review

Many of these products contain active moieties that have not been approved

by FDA previously, either as a single ingredient or as part of a combination

products; these products frequently provide important new therapies for the

patients.

Some drugs are characterized as NMEs for administrative purposes ,but

nonetheless contain certain active moieties in products that have been

previously approved by FDA. For example, CDER classifies biological

products submitted in an application under section 351(a) of the Public

Service Act as NME for purposes of FDA review, regardless of whether

the agency previously approved a related active moiety in a different

product.

FDAs classification of a drug as an -NME- for review purposes is distinct

from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-

within the meaning of the Federal Food,Drug, and Cosmetic Act

No.13

Drug Name - Eluxodoline

Active Ingredient- Viberzi

Date of approval - 5/27/2015

FDA-approved use - To treat irritable bowel syndrome with diarrhea (IBS-D) in adult men and women

Approved by US FDA on 5/27/2015- (Ref- FDA approved List- 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 Reaction:

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

abdominal pain.

Contra-Indications:

CONTRAINDICATIONS

Patients with:

1. known or suspected biliary duct obstruction, or sphincter of Oddi disease

or dysfunction

2.alcoholism, alcohol abuse, alcohol addiction, or drink more than

3 alcoholic beverages/day

3.a history of pancreatitis; structural diseases of the pancreas,

including known or suspected pancreatic duct obstruction

4.severe hepatic impairment (Child-Pugh Class C)

5.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.

Dosages/ Overdosage Etc:

INDICATIONS AND USAGE

VIBERZI is a mu-opioid receptor agonist, indicated in adults for the treatment

of irritable bowel syndrome with diarrhea (IBS-D).

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:

- do not have a gallbladder

- are unable to tolerate the 100 mg dose

- are receiving concomitant OATP1B1 inhibitors

- 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

75mg and 100 mg tablets

Patient Information:

PATIENT COUNSELING INFORMATION

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

Instruct patients to:

1.stop VIBERZI and seek medical attention if unusual or severe abdominal pain

develops, especially if they do not have a gallbladder

2.avoid chronic or acute excessive alcohol use while taking VIBERZI.

3.take one tablet twice daily with food.

4.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.

5.call their healthcare provider if they are unable to tolerate VIBERZI

6.discontinue VIBERZI and call their health care provider if they experience

constipation lasting more than 4 days

7.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

Pharmacology/ Pharmacokinetics:

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. 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.

2. Pharmacokinetics

Following oral administration of 100 mg VIBERZI in healthy subjects, the Cmax of

eluxadoline was approximately 2 to 4 ng/mL and AUC was 12 to 22 ng.h/mL.

Eluxadoline has approximately linear pharmacokinetics with no accumulation

upon repeated twice daily dosing. The variability of eluxadoline pharmacokinetic

parameters ranges from 51% to 98%.

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

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. 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

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

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.

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%).

Plasma concentrations of eluxadoline increase in patients with hepatic impairment [see Clinical Pharmacology (12.3)].

VIBERZI*

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation