[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/) › Sofosbuvir + velpatasvir + voxilaprevir

# Sofosbuvir + velpatasvir + voxilaprevir

## Hepatitis C direct-acting antivirals?

Hepatitis C direct-acting antivirals

A three-drug hepatitis C tablet for people whose earlier direct-acting antiviral treatment failed. It covers all genotypes.

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 NS5B polymerase (sofosbuvir), NS5A (velpatasvir) and NS3/4A protease (voxilaprevir)

**Used for**
Chronic hepatitis C

**Key effects**
Headache · Tiredness · Diarrhoea

**Monitor**
HBsAg and anti-HBc before starting · Liver enzymes

**ATC**
J05AP56

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 NS5B polymerase (sofosbuvir), NS5A (velpatasvir) and NS3/4A protease (voxilaprevir)**Sofosbuvir + velpatasvir + voxilaprevir

ⓘ The figure shows voxilaprevir in the active site of the HCV NS3/4A protease, one of the three targets.

**Target in 3D:** HCV NS5B polymerase (sofosbuvir), NS5A (velpatasvir) and NS3/4A protease (voxilaprevir). PDB structure 6NZT (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6NZT) · Drag to rotate · pinch to zoom

The tablet blocks three viral steps at once. Sofosbuvir is a nucleotide prodrug whose triphosphate is built into the viral RNA by the NS5B polymerase and stops chain growth. Velpatasvir inhibits NS5A, needed for replication and assembly. Voxilaprevir blocks the NS3/4A protease that cuts the viral polyprotein. Three targets make the combination effective even after failure of an NS5A-containing regimen.

- Sofosbuvir stops RNA synthesis by NS5B
- Velpatasvir blocks NS5A replication and assembly
- Voxilaprevir blocks the NS3/4A protease
- Three targets overcome earlier resistance

## Indications

- Chronic hepatitis C, all genotypes, in adults previously treated with a direct-acting antiviral regimen (retreatment) [Viral hepatitis →](https://durgical.com/en/conditions/viral-hepatitis/)

## Adverse effects

### Common

- Headache
- Tiredness
- Diarrhoea
- Nausea
- Insomnia and low mood

### Serious (rare, important)

- Hepatitis B reactivation
- Severe bradycardia when combined with amiodarone
- Liver injury or decompensation in advanced liver disease

## Contraindications

- Rifampicin (and other strong inducers of P-gp or CYP3A)
- Moderate or severe hepatic impairment (decompensated cirrhosis)

## Key interactions

**Amiodarone**
Severe, sometimes fatal bradycardia with sofosbuvir; avoided or closely monitored

**Ciclosporin (strong OATP1B1 inhibitor)**
Raises voxilaprevir; not combined

**Rosuvastatin, methotrexate and other BCRP substrates**
Voxilaprevir raises their levels; avoided

**Antacids with aluminium or magnesium**
Lower velpatasvir absorption; doses are separated in time

## What is monitored

- HBsAg and anti-HBc before starting
- Heart rate if amiodarone was used recently
- Liver enzymes
- HCV RNA after treatment

## Administration and safety

- One tablet by mouth with food
- Antacids are separated from the tablet by several hours
- 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

- Review cardiac drugs, especially amiodarone, before starting
- Check hepatitis B status
- Teach to report fainting, slow pulse or breathlessness
- Teach to report jaundice, abdominal swelling or black stools

## Pharmacokinetics

**Absorption**
Oral, with food (food raises voxilaprevir exposure)

**Metabolism**
Voxilaprevir is a substrate of CYP3A4, CYP2C8, CYP1A2, P-gp, BCRP and OATP1B1/3, and inhibits P-gp, BCRP and OATP1B1/3

**Elimination**
Voxilaprevir mainly in bile and faeces

## Memory aid

SOF-VEL-VOX: the third «V» comes in when the first round of hepatitis C treatment failed.

## Test yourself

Think of the answer, then tap the question to see it.

## When is sofosbuvir + velpatasvir + voxilaprevir used?

For retreatment of chronic hepatitis C after failure of an earlier direct-acting antiviral regimen.

## Which drug in the tablet blocks the NS3/4A protease?

Voxilaprevir.

## Which heart drug is dangerous with sofosbuvir-containing regimens?

Amiodarone, because of severe bradycardia.

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

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

## Connections

## Related drugs 3

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

## 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: [Sofosbuvir, Velpatasvir, and Voxilaprevir: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a617037.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AP56) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [Crystal structure of HCV NS3/4A protease in complex with voxilaprevir](https://www.rcsb.org/structure/6NZT) (RCSB Protein Data Bank, 2019).

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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/sofosbuvir-velpatasvir-voxilaprevir/