[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/hepatitis-c-direct-acting-antivirals/) › Elbasvir + grazoprevir

# 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.

Updated Nov 1, 2026

## Quick facts

**Group**
[Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

✂**HCV NS3/4A protease (grazoprevir) and NS5A protein (elbasvir)**Elbasvir + grazoprevir

ⓘ The figure shows grazoprevir (MK-5172) in the active site of the HCV NS3/4A protease; elbasvir acts on a different viral protein, NS5A.

**Target in 3D:** HCV NS3/4A protease (grazoprevir) and NS5A protein (elbasvir). PDB structure 3SUD (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/3SUD) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/viral-hepatitis/)

## Adverse effects

### Common

- Headache
- Tiredness
- Nausea
- Diarrhoea and insomnia

### Serious (rare, important)

- Hepatitis B reactivation in people with past or current HBV infection
- Raised liver enzymes
- Liver decompensation in advanced cirrhosis

## 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

## Memory aid

EL-GRAZ: two hooks, one in the protease (GRAZoprevir), one in NS5A (ELbasvir); the kidneys can stay out of it.

## 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.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/elbasvir-grazoprevir/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 3

- [Sofosbuvir + velpatasvir](https://durgical.com/en/pharmacology/sofosbuvir-velpatasvir/)
- [Glecaprevir + pibrentasvir](https://durgical.com/en/pharmacology/glecaprevir-pibrentasvir/)
- [Ribavirin](https://durgical.com/en/pharmacology/ribavirin/)

## Related conditions 1

- [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/)

[← Back to the class: Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/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](https://medlineplus.gov/druginfo/meds/a616016.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AP54) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [Crystal structure of NS3/4A protease in complex with MK-5172](https://www.rcsb.org/structure/3SUD) (RCSB Protein Data Bank, 2012).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/elbasvir-grazoprevir/