Elbasvir + grazoprevir
Hepatitis C direct-acting antivirals
Hepatitis C direct-acting antivirals
A tablet for hepatitis C genotypes 1 and 4 that combines an NS5A inhibitor and an NS3/4A protease inhibitor; usable in severe kidney disease.
Quick facts
- Group
- Hepatitis C direct-acting antivirals
- Target
- HCV NS3/4A protease (grazoprevir) and NS5A protein (elbasvir)
- Used for
- Chronic hepatitis C genotypes 1 and 4
- Key effects
- Headache · Tiredness · Nausea
- Monitor
- HBsAg and anti-HBc before starting
- ATC
- J05AP54
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows grazoprevir (MK-5172) in the active site of the HCV NS3/4A protease; elbasvir acts on a different viral protein, NS5A.
Grazoprevir blocks the NS3/4A serine protease that cuts the HCV polyprotein into working proteins. Elbasvir binds NS5A, a protein needed for viral RNA replication and virion assembly. Together they block two steps of the viral life cycle and have a high barrier to resistance. Pre-existing NS5A resistance-associated substitutions lower response in genotype 1a, so they are tested before treatment.
- Grazoprevir blocks the NS3/4A protease
- The viral polyprotein is not cut into working parts
- Elbasvir blocks NS5A replication and assembly
- HCV replication stops; sustained response follows
Indications
- Chronic hepatitis C genotypes 1 and 4, with or without ribavirin, including people with advanced kidney disease Viral hepatitis →
Adverse effects
Common
- Headache
- Tiredness
- Nausea
- Diarrhoea and insomnia
Contraindications
- Moderate or severe hepatic impairment (decompensated cirrhosis)
- OATP1B1 inhibitors such as HIV protease inhibitors
- Strong CYP3A inducers such as rifampicin, efavirenz or St John's wort
Key interactions
- HIV protease inhibitors (OATP1B1 inhibitors)
- Raise grazoprevir levels and the risk of liver injury; not combined
- Efavirenz and other strong CYP3A or P-gp inducers
- Lower both drugs and risk treatment failure; not combined
- St John's wort
- Lowers levels; avoided
What is monitored
- HBsAg and anti-HBc before starting
- Liver enzymes before and during treatment
- HCV RNA to confirm sustained virological response
- NS5A resistance testing in genotype 1a
Administration and safety
- One fixed-dose tablet by mouth, with or without food
- The full course is completed even when the person feels well
Pregnancy and breastfeeding
Safety in pregnancy is not established; benefit and risk are weighed.
Nursing care
- Check hepatitis B status before the first dose
- Reconcile HIV medicines and herbal products
- Teach to report jaundice, dark urine, abdominal swelling or black stools
- Explain the importance of the follow-up HCV RNA test
Pharmacokinetics
- Absorption
- Oral, with or without food
- Metabolism
- Both are CYP3A substrates; grazoprevir also needs OATP1B1 for liver uptake
- Elimination
- Mainly in the faeces; very little by the kidneys, so it is used in kidney failure
Test yourself
Think of the answer, then tap the question to see it.
Which HCV proteins do elbasvir and grazoprevir block?
Elbasvir blocks NS5A; grazoprevir blocks the NS3/4A protease.
Why is this combination useful in severe kidney disease?
Both drugs are cleared mainly by the liver, with very little renal elimination.
Why are HIV protease inhibitors not combined with it?
They inhibit OATP1B1 and raise grazoprevir levels, increasing the risk of liver injury.
Connections
← Back to the class: Hepatitis C direct-acting antivirals
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Elbasvir and Grazoprevir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Crystal structure of NS3/4A protease in complex with MK-5172 (RCSB Protein Data Bank, 2012).
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Representative model, for educational purposes only.