Eluxadoline- Viberzi- @- (May 2015) -Gastro-Intestinal
Drug Name:Eluxadoline- Viberzi- @- (May 2015) -Gastro-Intestinal
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
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)].
