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