Elbasvir / grazoprevir

Elbasvir / grazoprevir
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: AKT

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Black Box Warning

TITLE RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV See full prescribing information for complete Boxed Warning. Condition Name: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ZEPATIER. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

Overview

Elbasvir / grazoprevir is a combination of a hepatitis C virus NS5A inhibitor and a Hepatitis C virus NS3/4A protease inhibitor that is FDA approved for the treatment of chronic HCV genotype 1 or 4 infection in adults. There is a Black Box Warning for this drug as shown here. Common adverse reactions include {{{adverseReactions}}}.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

ZEPATIER is indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults. ZEPATIER is indicated for use with ribavirin in certain patient populations. Dosing Information

• ZEPATIER is a two-drug, fixed-dose combination product containing 50 mg of elbasvir and 100 mg of grazoprevir in a single tablet.
• The recommended dosage of ZEPATIER is one tablet taken orally once daily with or without food. *ZEPATIER is used in combination with ribavirin in certain patient populations (see TABLE 1). When administered with ZEPATIER, the recommended dosage of ribavirin in patients without renal impairment is weight-based administered in two divided doses with food. For further information on ribavirin dosing and dosage modifications, refer to the ribavirin prescribing information.
• Treatment Regimen and Duration of Therapy
  • Relapse rates are affected by baseline host and viral factors and differ between treatment regimens and durations for certain subgroups
  • TABLE 1 below provides the recommended ZEPATIER treatment regimen and duration based on the patient population and genotype in HCV mono-infected and HCV/HIV-1 co-infected patients with or without cirrhosis and with or without renal impairment including patients receiving hemodialysis.

TABLE 1

• Renal Impairment
  • No dosage adjustment of ZEPATIER is recommended in patients with any degree of renal impairment including patients on hemodialysis. Administer ZEPATIER with or without ribavirin according to the recommendations in TABLE 1. Refer to the ribavirin tablet prescribing information for the correct ribavirin dosage for patients with CrCl less than or equal to 50 mL per minute.
• 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 or severe hepatic impairment (Child-Pugh B or C)

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Elbasvir and grazoprevir in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Elbasvir and grazoprevir in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Elbasvir / grazoprevir FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Elbasvir and grazoprevir in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Elbasvir and grazoprevir in pediatric patients.

Contraindications

• ZEPATIER is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) due to the expected significantly increased grazoprevir plasma concentration and the increased risk of alanine aminotransferase (ALT) elevations.
• ZEPATIER is contraindicated with inhibitors of organic anion transporting polypeptides 1B1/3 (OATP1B1/3) that are known or expected to significantly increase grazoprevir plasma concentrations, strong inducers of cytochrome P450 3A (CYP3A), and efavirenz.
• If ZEPATIER is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen. Refer to the ribavirin prescribing information for a list of contraindications for ribavirin.

TABLE 2

Warnings

TITLE RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV See full prescribing information for complete Boxed Warning. Condition Name: Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with ZEPATIER. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.

• Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV
  • Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals, and who were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure and death. Cases have been reported in patients who are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive). HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients.
  • HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis, i.e., increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur.
  • Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment with ZEPATIER. In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment with ZEPATIER and during post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
• Increased Risk of ALT Elevations
  • During clinical trials with ZEPATIER with or without ribavirin, 1% of subjects experienced elevations of ALT from normal levels to greater than 5 times the upper limit of normal (ULN), generally at or after treatment week 8. ALT elevations were typically asymptomatic and most resolved with ongoing or completion of therapy. Higher rates of late ALT elevations occurred in the following subpopulations: female sex (2% [10/608]), Asian race (2% [4/164]), and age 65 years or older (2% [3/177])
  • Hepatic laboratory testing should be performed prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic laboratory testing should be performed at treatment week 12.
  • Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice, or discolored feces.
  • Consider discontinuing ZEPATIER if ALT levels remain persistently greater than 10 times the ULN.
  • Discontinue ZEPATIER if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
• Risks Associated with Ribavirin Combination Treatment
  • If ZEPATIER is administered with ribavirin, the warnings and precautions for ribavirin, including the pregnancy avoidance warning, also apply to this combination regimen. Refer to the ribavirin prescribing information for a full list of warnings and precautions for ribavirin
• Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug Interactions
  • The concomitant use of ZEPATIER and certain drugs may result in known or potentially significant drug interactions, some of which may lead to:
    • Possible clinically significant adverse reactions from greater exposure of concomitant drugs or components of ZEPATIER.
    • Significant decrease of elbasvir and grazoprevir plasma concentrations which may lead to reduced therapeutic effect of ZEPATIER and possible development of resistance.
  • See TABLES 2 and 6 for steps to prevent or manage these known or potentially significant drug interactions, including dosing recommendations.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Elbasvir / grazoprevir Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Elbasvir / grazoprevir Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Elbasvir / grazoprevir Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Elbasvir / grazoprevir in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Elbasvir / grazoprevir in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Elbasvir / grazoprevir during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Elbasvir / grazoprevir in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Elbasvir / grazoprevir in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Elbasvir / grazoprevir in geriatric settings.

Gender

There is no FDA guidance on the use of Elbasvir / grazoprevir with respect to specific gender populations.

Race

There is no FDA guidance on the use of Elbasvir / grazoprevir with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Elbasvir / grazoprevir in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Elbasvir / grazoprevir in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Elbasvir / grazoprevir in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Elbasvir / grazoprevir in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Elbasvir / grazoprevir Administration in the drug label.

Monitoring

There is limited information regarding Elbasvir / grazoprevir Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Elbasvir / grazoprevir and IV administrations.

Overdosage

There is limited information regarding Elbasvir / grazoprevir overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Elbasvir / grazoprevir Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Elbasvir / grazoprevir Mechanism of Action in the drug label.

Structure

There is limited information regarding Elbasvir / grazoprevir Structure in the drug label.

Pharmacodynamics

There is limited information regarding Elbasvir / grazoprevir Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Elbasvir / grazoprevir Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Elbasvir / grazoprevir Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Elbasvir / grazoprevir Clinical Studies in the drug label.

How Supplied

There is limited information regarding Elbasvir / grazoprevir How Supplied in the drug label.

Storage

There is limited information regarding Elbasvir / grazoprevir Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Elbasvir / grazoprevir Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Elbasvir and grazoprevir interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Elbasvir / grazoprevir Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Elbasvir / grazoprevir Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.