Usual Adult Dose for Chronic Hepatitis C

1 tablet orally once a day

Recommended Regimen and Duration of Therapy:

• Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced without baseline nonstructural protein 5A (NS5A) polymorphisms: Elbasvir-grazoprevir for 12 weeks
• Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced with baseline NS5A polymorphisms: Elbasvir-grazoprevir plus ribavirin for 16 weeks
• Genotype 1b, therapy-naive or peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir for 12 weeks
• Genotype 1a or 1b, peginterferon alfa/ribavirin/HCV protease inhibitor-experienced: Elbasvir-grazoprevir plus ribavirin for 12 weeks
• Genotype 4, therapy-naive: Elbasvir-grazoprevir for 12 weeks
• Genotype 4, peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir plus ribavirin for 16 weeks

• This drug should be used with ribavirin in certain patient populations.
• Hepatic laboratory testing recommended prior to and during therapy.
• Peginterferon alfa/ribavirin-experienced: Patients who have failed therapy with peginterferon alfa plus ribavirin
• Baseline NS5A polymorphisms: NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93.
• Peginterferon alfa/ribavirin/HCV protease inhibitor-experienced: Patients who have failed therapy with peginterferon alfa plus ribavirin plus HCV NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, telaprevir)
• Optimal regimen and duration of therapy not established for peginterferon alfa/ribavirin/HCV protease inhibitor-experienced genotype 1a-infected patients with at least 1 baseline NS5A resistance-associated polymorphism at positions 28, 30, 31, and 93.
• The manufacturer product information for ribavirin tablets should be consulted regarding dosing and dose adjustments (if applicable).

Usual Pediatric Dose for Chronic Hepatitis C

12 years and older OR weighing at least 30 kg: 1 tablet orally once a day

Recommended Regimen and Duration of Therapy:

• Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced without baseline NS5A polymorphisms: Elbasvir-grazoprevir for 12 weeks
• Genotype 1a, therapy-naive or peginterferon alfa/ribavirin-experienced with baseline NS5A polymorphisms: Elbasvir-grazoprevir plus ribavirin for 16 weeks
• Genotype 1b, therapy-naive or peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir for 12 weeks
• Genotype 1a or 1b, peginterferon alfa/ribavirin/HCV protease inhibitor-experienced: Elbasvir-grazoprevir plus ribavirin for 12 weeks
• Genotype 4, therapy-naive: Elbasvir-grazoprevir for 12 weeks
• Genotype 4, peginterferon alfa/ribavirin-experienced: Elbasvir-grazoprevir plus ribavirin for 16 weeks

• This drug should be used with ribavirin in certain patient populations.
• Hepatic laboratory testing recommended prior to and during therapy.
• Peginterferon alfa/ribavirin-experienced: Patients who have failed therapy with peginterferon alfa plus ribavirin
• Baseline NS5A polymorphisms: NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93.
• Peginterferon alfa/ribavirin/HCV protease inhibitor-experienced: Patients who have failed therapy with peginterferon alfa plus ribavirin plus HCV NS3/4A protease inhibitor (e.g., boceprevir, simeprevir, telaprevir)
• Optimal regimen and duration of therapy not established for peginterferon alfa/ribavirin/HCV protease inhibitor-experienced genotype 1a-infected patients with at least 1 baseline NS5A resistance-associated polymorphism at positions 28, 30, 31, and 93.
• The manufacturer product information for ribavirin tablets should be consulted regarding dosing and dose adjustments (if applicable).

Renal Dose Adjustments

Any degree of renal dysfunction: No adjustment recommended.

Comments:

• The manufacturer product information for ribavirin tablets should be consulted regarding use in patients with CrCl up to 50 mL/min (if applicable).

Liver Dose Adjustments

Mild liver dysfunction (Child-Pugh A): No adjustment recommended.
Moderate or severe liver dysfunction (Child-Pugh B or C) or any history of hepatic decompensation: Contraindicated

Precautions

US BOXED WARNING:

• RISK OF HBV REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: All patients should be tested for evidence of current/prior HBV infection before starting this drug. HBV reactivation has been reported during or after completion of HCV direct-acting antiviral therapy in HCV/HBV-coinfected patients who were not receiving HBV antiviral therapy; some cases resulted in fulminant hepatitis, hepatic failure, and death. HCV/HBV-coinfected patients should be monitored for hepatitis flare or HBV reactivation during HCV therapy and posttherapy follow-up; appropriate patient management for HBV infection should be started as clinically indicated.

• Moderate or severe liver dysfunction (Child-Pugh B or C) or any history of hepatic decompensation
• Coadministration with inhibitors of OATP1B1/3 known/expected to significantly increase grazoprevir plasma levels, strong CYP450 3A inducers, efavirenz, phenytoin, carbamazepine, rifampin, St. John's wort, atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cyclosporine; this is not a complete list of all strong CYP450 3A inducers and may not include all OATP1B1/3 inhibitors that significantly increase grazoprevir plasma levels
• Combination Therapy: Contraindications to ribavirin

Dialysis

Hemodialysis: No adjustment recommended.
Peritoneal dialysis: Data not available

Comments:

• The manufacturer product information for ribavirin tablets should be consulted regarding use in patients receiving hemodialysis (if applicable).

Other Comments

Administration advice:

• Before starting this drug, test all patients for evidence of current/prior HBV infection; measure hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
• Before starting this drug, test patients with HCV genotype 1a infection for virus with NS5A resistance-associated polymorphisms to determine dose regimen and duration.
• Administer with or without food.
• Consult the manufacturer product information regarding missed doses.

• Store at 20C to 25C (68F to 77F); excursions permitted between 15C to 30C (59F to 86F).
• Store in original package until use to protect from moisture.

• Each fixed-dose combination tablet contains elbasvir 50 mg and grazoprevir 100 mg.
• In patients using this drug for 12 weeks, sustained virologic response rates were lower in genotype 1a-infected patients with at least 1 baseline NS5A resistance-associated polymorphism at amino acid positions 28, 30, 31, or 93.
• Relapse rates are affected by baseline host and viral factors and differ between treatment regimens and durations for certain subgroups.
• The manufacturer product information for ribavirin should be consulted for additional information.

• General: For clinical and laboratory signs of hepatitis flare or HBV reactivation in patients with serological evidence of HBV infection (during HCV therapy with this drug and during posttreatment follow-up)
• Hepatic: Hepatic laboratory tests in all patients (before therapy, at treatment week 8, at treatment week 12 [if 16-week regimen], and as clinically indicated; more often in those with compensated cirrhosis [Child-Pugh A] or evidence of advanced liver disease); for signs/symptoms of hepatic decompensation

• Read the US FDA-approved patient information (Patient Information) for this drug and review the Medication Guide for ribavirin, if applicable.
• Seek medical evaluation at once for symptoms of worsening liver problems (e.g., nausea, tiredness, yellowing of the skin/white part of the eyes, bleeding/bruising more easily than normal, confusion, loss of appetite, diarrhea, dark/brown urine, dark/bloody stool, swelling of the stomach area [abdomen]/pain in the upper right side of the stomach area, sleepiness, vomiting of blood).
• Watch for signs of liver inflammation (e.g., early signs: fatigue, weakness, lack of appetite, nausea and vomiting; later signs: jaundice, discolored feces); consult healthcare provider immediately if these symptoms develop.
• Avoid missing doses and complete the entire course of therapy.

Frequently asked questions

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