Elbasvir and Grazoprevir - Zepatier -@- (Jan 2016)- Antiviral agent
Drug Name:Elbasvir and Grazoprevir - Zepatier -@- (Jan 2016)- Antiviral agent
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:
DRUG INTERACTIONS
Co-administration of ZEPATIER with moderate CYP3A inducers is
not recommended as they may decrease the plasma concentration
of ZEPATIER.
Co-administration of ZEPATIER with certain strong CYP3A inhibitors
is not recommended as they may increase the plasma concentration
of ZEPATIER.
Consult the full prescribing information prior to and during treatment
for potential drug interactions.
Indication:
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use on Approval date
1. Zepatier Elbasvir and 1/28/2016 To treat patients with chronic
Grazoprevir Hepatitis C Virus (HCV)
genoytpes 1 and 4 infections
in adult patients
Press Release
Drug trials Snapshot
Approved by FDA on 1/28/2016 (Ref- FDA approved List- 2016)
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
ZEPATIER safely and effectively. See full prescribing information
for ZEPATIER.
ZEPATIER (elbasvir and grazoprevir) tablets, for oral use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
ZEPATIER is a fixed-dose combination product containing elbasvir, a
hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV
NS3/4A protease inhibitor, and is indicated with or without r bavirin for
treatment of chronic HCV genotypes 1 or 4 infection in adults.
Adverse Reaction:
ADVERSE REACTIONS
In subjects receiving ZEPATIER for 12 weeks, the most commonly
reported adverse reactions of all intensity (greater than or equal to 5%
in placebo-controlled trials) were fatigue, headache, and nausea.
In subjects receiving ZEPATIER with ribavirin for 16 weeks, the most
commonly reported adverse reactions of moderate or severe intensity
(greater than or equal to 5%) were anemia and headache.
Contra-Indications:
CONTRAINDICATIONS
Patients with moderate or severe hepatic impairment (Child-Pugh B
or C). OATP1B1/3 inhibitors, strong CYP3A inducers, and efavirenz.
If ZEPATIER is administered with ribavirin, the contraindications to
ribavirin also apply.
WARNINGS AND PRECAUTIONS
ALT elevations: Perform hepatic laboratory testing prior to therapy,
at treatment week 8, and as clinically indicated.
For patients receiving 16 weeks of therapy, perform additional hepatic laboratory
testing at treatment week 12.
For ALT elevations on ZEPATIER, follow recommendations in full prescribing
information.
Risk associated with ribavirin combination treatment:
If ZEPATIER is administered with ribavirin, the warnings and precautions for
ribavirin also apply.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
ZEPATIER is a fixed-dose combination product containing elbasvir, a
hepatitis C virus (HCV) NS5A inhibitor, and grazoprevir, an HCV
NS3/4A protease inhibitor, and is indicated with or without r bavirin for
treatment of chronic HCV genotypes 1 or 4 infection in adults.
DOSAGE AND ADMINISTRATION
Testing prior to initiation:
Genotype 1a: Testing for the presence of virus with NS5A
resistance-associated polymorphisms is recommended.
Obtain hepatic laboratory testing.
Recommended dosage: One tablet taken orally once daily with or
without food.
DOSAGE FORMS AND STRENGTHS
Tablets: 50 mg e basvir and 100 mg grazoprevir
OVERDOSAGE
Human experience of overdose with ZEPATIER is limited. No specific antidote is available for overdose with ZEPATIER. In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.
Hemodialysis does not remove elbasvir or grazoprevir since elbasvir and grazoprevir are highly bound to plasma protein.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
1. For patients receiving ZEPATIER with ribavirin, advise patients to read the
FDA-approved patient labeling (Medication Guide) for ribavirin
2. Risk of ALT Elevations
Inform patients to watch for early warning signs of liver inflammation, such as fatigue,
weakness,lack of appetite, nausea and vomiting, as well as later signs such
as jaundice and discolored feces, and to consult their healthcare professional
without delay if such symptoms occur.
.
3.Pregnancy
Advise patients taking ZEPATIER with ribavirin to avoid pregnancy during treatment
and within 6 months of stopping ribavirin and to notify their healthcare provider
immediately in the event of a pregnancy .
4.Drug Interactions
Inform patients that ZEPATIER may interact with some drugs; therefore, advise
patients to report the use of any prescription, non-prescription medication,
or herbal products to their healthcare provider
5.Storage
Advise patients to store ZEPATIER in the original package until use to protect
from moisture.
6.Administration
Advise patients to take ZEPATIER every day at the regularly scheduled time
with or without food.
Inform patients that it is important not to miss or skip doses and to take
ZEPATIER for the duration that is recommended by the healthcare provider.
Manufactured by:
MSD International GmbH, Ballydine, Clonmel, Ireland
For patent information: www.merck.com/product/patent/home.html
Copyright © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & C
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
ZEPATIER is a fixed-dose combination of elbasvir and grazoprevir which are
direct-acting antiviral agents against the hepatitis C virus.
2. Pharmacokinetics
The pharmacokinetic properties of elbasvir and grazoprevir have been evaluated
in non-HCVinfected adult subjects and in HCV-infected adult subjects.
Elbasvir pharmacokinetics were similar in healthy subjects and HCV-infected
subjects and were approximately dose-proportional over the range of
5-100 mg once daily.
Grazoprevir oral exposures are approximately 2-fold greater in HCV-infected
subjects as compared to healthy subjects.
Grazoprevir pharmacokinetics increased in a greater than dose-proportional
manner over the range of 10-800 mg once daily in HCV-infected subjects.
Ribavirin coadministration with ZEPATIER had no clinically relevant impact
on plasma AUC and Cmax of elbasvir and grazoprevir compared to administration
of ZEPATIER alone.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
No adequate human data are available to establish whether or not ZEPATIER
poses a risk to pregnancy outcomes.
In animal reproduction studies, no evidence of adverse developmental outcomes
was observed with the components of ZEPATIER (elbasvir or grazoprevir)
at exposures greater than those in humans at the recommended human
dose (RHD)
The background risk of major birth defects and miscarriage for the indicated
population is unknown. In the U.S. general population, the estimated background
risk of major birth defects and miscarriage in clinically recognized pregnancies
is 2-4% and 15-20%, respectively.
If ZEPATIER is administered with ribavirin, the combination regimen is
contraindicated in pregnant women and in men whose female partners are pregnant.
Refer to the ribavirin prescribing information for more information on use in pregnancy.
2. Lactation
Risk Summary
It is not known whether ZEPATIER is present in human breast milk, affects human
milk production, or has effects on the breastfed infant.
When administered to lactating rats, the components of ZEPATIER
(elbasvir and grazoprevir) were present in milk, without effects on growth and
development observed in nursing pups
The developmental and health benefits of breastfeeding should be considered
along with the mothers clinical need for ZEPATIER and any potential adverse
effects on the breastfed child from ZEPATIER or from the underlying maternal condition.
3. Pediatric Use
Safety and efficacy in pediatric patients have not been established in pediatric
patients less than 18 years of age.
4. Geriatric Use
Clinical trials of ZEPATIER with or without ribavirin included 187 subjects
aged 65 years and over. Higher elbasvir and grazoprevir plasma concentrations
were observed in subjects aged 65 years and over.
A higher rate of late ALT elevations was observed in subjects aged 65 years
and over in clinical trials.
However, no dosage adjustment of ZEPATIER is recommended in geriatric
patients .
5 Gender
Higher elbasvir and grazoprevir plasma concentrations were observed in females
compared to males. Females experienced a higher rate of late ALT elevations
in clinical trials .
However, no dose adjustment of ZEPATIER is recommended based on gender.
6. Race
Higher elbasvir and grazoprevir plasma concentrations were observed in
Asians compared to Caucasians. Asians experienced a higher rate of late
ALT elevations in clinical trials.
However, no dose adjustment of ZEPATIER is recommended based on
race/ethnicity
7. Renal Impairment
No dosage adjustment of ZEPATIER is recommended in patients with any
degree of renal impairment including patients receiving hemodialysis.
Administer ZEPATIER with or without ribavirin according to
recommendations.
Refer to the prescribing information for ribavirin tablets for renal dosage
adjustment of ribavirin in patients with CrCl less than or equal to 50 mL per minute.
8. Hepatic Impairment
No dosage adjustment of ZEPATIER is recommended in patients with mild hepatic
impairment (Child-Pugh A).
ZEPATIER is contraindicated in patients with moderate hepatic impairment
(Child-Pugh B) due to the lack of clinical safety and efficacy experience
in HCV-infected Child-Pugh B patients, and in patients with severe hepatic
impairment (Child-Pugh C) due to a 12-fold increase in grazoprevir exposure
in non-HCV infected Child-Pugh C subjects,
The safety and efficacy of ZEPATIER have not been established in patients awaiting liver
transplant or in liver transplant recipient
