Elbasvir + Grazoprevir
Indications
Elbasvir + Grazoprevir is used for:
Chronic Hepatitis C, Indicated with or without ribavirin for treatment of chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in adults
Adult Dose
Oral
Chronic Hepatitis C
Indicated with or without ribavirin for treatment of chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in adults
1 tablet PO qDay; treatment duration and whether to take with or without ribavirin are dependent on genotypes and other patient variable
Treatment regimen and duration of therapy
Patients with or without cirrhosis
Genotypes 1a
Treatment-naïve or PegIFN/RBV-experienced without baseline NS5A polymorphisms: elbasvir/grazoprevir for 12 wk
Treatment-naïve or PegIFN/RBV-experienced WITH baseline NS5A polymorphisms: elbasvir/grazoprevir plus weight-based ribavirin for 16 wk
Genotype 1b
Treatment-naïve or PegIFN/RBV-experienced: elbasvir/grazoprevir for 12 wk
Genotypes 1a or 1b
PegIFN/RBV/PI-experienced: elbasvir/grazoprevir plus weight-based ribavirin for 12 wk
Genotype 4
Treatment-naïve: elbasvir/grazoprevir for 12 wk
Peg/IFN/RBV-experienced: elbasvir/grazoprevir plus weight-based ribavirin for 16 wk
Hepatic impairment
Mild (Child-Pugh A): No dosage adjustment required
Moderate-to-severe (Child Pugh B or C): Contraindicated
Child Dose
Renal Dose
Renal impairment
No dosage adjustment is required for patients with any degree of renal impairment including patients on hemodialysis
Refer to the ribavirin prescribing information for dose in patients with CrCl ?50 mL/min
Administration
May take with or without food
Contra Indications
Patients with moderate or severe hepatic impairment (Child Pugh B or C) because of significantly increased grazoprevir plasma concentration and risk of increased ALT levels
If administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen (refer to ribavirin prescribing information)
Organic anion transporting polypeptides 1B1/3 (OATP1B1/3) inhibitors, strong CYP3A inducers, and efavirenz
Precautions
Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV DDAs, and who were not receiving HBV antiviral therapy; HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level
May increase ALT levels; measure liver enzymes 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
Warnings and precautions (including pregnancy) for ribavirin apply if coadministered
Risk of adverse reactions or reduced therapeutic effect caused by drug interactions
Pregnancy-Lactation
Pregnancy
No adequate human data are available
In animal reproduction studies, no evidence of adverse developmental outcomes was observed with elbasvir or grazoprevir at exposures greater than those in humans at the recommended human dose
Note: Ribavirin is contraindicated in pregnant women and men whose female partners are pregnant
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding, along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Interactions
Adverse Effects
Side effects of Elbasvir + Grazoprevir :
>10%
Fatigue, treatment-naïve (11%)
1-10%
Headache, treatment-naïve (10%)
Treatment-experienced
Fatigue (5%)
Abdominal pain (2%)
Diarrhea (2%)
Irritability (1%)
Depression (1%)
Mechanism of Action
Elbasvir: Inhibitor of HCV NS5A, which is essential for viral RNA replication and virion assembly
Grazoprevir: Inhibitor of HCV NS3/4A protease, which is necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication