Elbasvir/Grazoprevir

DEA Class; Rx

Common Brand Names; Zepatier

• HCV NS5A Inhibitors; 
• HCV NS3/4A Protease Inhibitors

Combination product containing an NS5A inhibitor (elbasvir) and an NS3/4A protease inhibitor (grazoprevir)
Used to treat adults and pediatric patients weighing at least 30 kg with HCV genotypes 1 and 4 infections
Contraindicated in patients with moderate to severe hepatic impairment or history of hepatic decompensation; potential for significant drug interactions

Patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of hepatic decompensation due to the risk of hepatic decompensation

If administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen (refer to ribavirin prescribing information)

Coadministration with OATP1B1/3 inhibitors

• Not a comprehensive list
• May increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition
• HIV medications: atazanavir, darunavir, lopinavir, saquinavir, tipranavir
• Immunosuppressants: cyclosporine

Coadministration with strong CYP3A inducers

• Not a comprehensive list May lead to loss of virologic response to elbasvir/grazoprevir owing to significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction
• Anticonvulsants: carbamazepine, phenytoin
• Antimycobacterials: rifampin
• Herbals: St John’s wort
• HIV medications: efavirenz

Adults

• Fatigue, treatment-naïve (5-11%)
• Headache, treatment-naïve (10-11%)

Pediatric patients

• Headache (14%)

1-10%

Adults

• Treatment-experienced
  • Fatigue (5%)
  • Abdominal pain (2%)
  • Diarrhea (2%)
  • Irritability (1%)
  • Depression (1%)
• Treatment-experienced plus ribavirin
  • Anemia (8%)
  • Headache (6%)
  • Fatigue (4%)
  • Dyspnea (4%)
  • Rash or pruritus (4%)
  • Irritability (3%)
  • Abdominal pain (2%)
  • Depression (2%)
  • Arthralgia (2%)

Pediatric patients

• Nausea (9%)

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 (see Black Box Warnings and Dosing Considerations)

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

Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, reported; in patients with compensated cirrhosis (Child-Pugh A) or evidence of advanced liver disease, such as portal hypertension, more frequent hepatic laboratory testing may be warranted; patients should be monitored for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage; discontinue therapy in patients who develop evidence of hepatic decompensation/failure

Warnings and precautions (including pregnancy) for ribavirin apply if coadministered

Risk of adverse reactions or reduced therapeutic effect caused by drug interactions (see Contraindications and Drug Interactions)

No adequate human data are available

Unknown if distributed in human breast milk

1 tablet/day PO (elbasvir 50 mg/day PO; grazoprevir 100 mg/day PO).

1 tablet/day PO (elbasvir 50 mg/day PO; grazoprevir 100 mg/day PO).

1 tablet/day PO (elbasvir 50 mg/day PO; grazoprevir 100 mg/day PO).

12 years: 1 tablet/day PO (elbasvir 50 mg/day PO; grazoprevir 100 mg/day PO).
younger than 12 years weighing 30 kg or more: 1 tablet/day PO (elbasvir 50 mg/day PO; grazoprevir 100 mg/day PO).
younger than 12 years weighing less than 30 kg: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.