[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

[Pharmacology](https://durgical.com/en/pharmacology/) · [Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/hepatitis-c-direct-acting-antivirals/)

# Sofosbuvir + velpatasvir

A pangenotypic pill for hepatitis C that WHO recommends; it cures most patients without the need to know the genotype.

Updated 2026-11-01

- Class: [Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/hepatitis-c-direct-acting-antivirals/)
- Enzyme: Hepatitis C virus NS5B polymerase (sofosbuvir) and NS5A protein (velpatasvir)
- ATC code: J05AP55
- WHO Model List of Essential Medicines

✂**Hepatitis C virus NS5B polymerase (sofosbuvir) and NS5A protein (velpatasvir)**Sofosbuvir + velpatasvir

ⓘ The figure shows the active diphosphate-level metabolite of sofosbuvir in the hepatitis C NS5B polymerase; no structure of NS5A with velpatasvir is available.

**Target in 3D:** Hepatitis C virus NS5B polymerase (sofosbuvir) and NS5A protein (velpatasvir). PDB structure 4WTG (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/4WTG) · Drag to rotate · pinch to zoom

## Mechanism of action

Two antivirals in one tablet. Sofosbuvir, a nucleotide prodrug, is converted to a uridine triphosphate analogue that NS5B incorporates into viral RNA, stopping the chain. Velpatasvir binds NS5A, a protein needed to build the replication complex and assemble new virions. Together they act on all genotypes with a high barrier to resistance.

- Sofosbuvir triphosphate stops RNA synthesis by NS5B
- Velpatasvir blocks NS5A
- Replication complex and virion assembly fail
- Viral RNA becomes undetectable: cure

## Pharmacokinetics

**Absorption**
Oral; velpatasvir needs gastric acid, so acid-reducing drugs lower its absorption

**Metabolism**
Sofosbuvir is activated in the liver and ends as the inactive metabolite GS-331007

**Elimination**
GS-331007 by the kidneys (filtration and tubular secretion)

**Half-life**
GS-331007 about 25 hours; velpatasvir about 15 hours

## Indications

- Chronic hepatitis C of any genotype (1 to 6), with or without compensated cirrhosis, in adults and children from 3 years [Viral hepatitis →](https://durgical.com/en/conditions/viral-hepatitis/)
- Decompensated cirrhosis, combined with ribavirin [Cirrhosis →](https://durgical.com/en/conditions/cirrhosis/)

## Adverse effects

### Common

- Headache
- Fatigue
- Nausea
- Insomnia

### Serious (rare, important)

- Hepatitis B reactivation in co-infected people
- Severe bradycardia with amiodarone
- Anaemia when ribavirin is added

## Contraindications

- When combined with ribavirin, the contraindications of ribavirin apply (pregnancy, among others)

## Key interactions

**Rifampicin, carbamazepine, phenytoin, St John's wort (strong inducers)**
Lower both drug levels; not recommended

**Antacids, H2 blockers, proton pump inhibitors**
Less velpatasvir absorption: antacids are separated by 4 hours and proton pump inhibitors are generally avoided

**Amiodarone**
Severe symptomatic bradycardia

**Tenofovir disoproxil**
Higher tenofovir levels: kidney monitoring

## What is monitored

- HBsAg and anti-HBc before starting; liver tests during and after
- HCV RNA 12 weeks after treatment ends (sustained virological response)
- INR in people on warfarin and glucose in diabetes, as liver function improves
- Haemoglobin when ribavirin is added

## Administration and safety

- One tablet a day
- Medicine list reviewed for amiodarone, inducers and acid-reducing drugs
- Antacids taken at least 4 hours apart

## Nursing care

- Review all medicines, including over-the-counter antacids and herbal products
- Teach to report slow pulse, dizziness or fainting
- Encourage completing all the weeks of treatment
- Explain that cure does not protect against reinfection

## Pregnancy and breastfeeding

Human data are lacking; animal studies showed no harm. With ribavirin it is contraindicated in pregnancy.

## Memory aid

SOF + VEL = «SOlves Every Lineage»: pangenotypic.

## Test yourself

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

## Why is sofosbuvir-velpatasvir called pangenotypic?

It is active against hepatitis C genotypes 1 to 6.

## Why are proton pump inhibitors a problem with this combination?

Velpatasvir needs gastric acid to dissolve; higher gastric pH lowers its absorption.

## What is added in decompensated cirrhosis?

Ribavirin.

## Which test defines cure after treatment?

Undetectable HCV RNA 12 weeks after the end of treatment (sustained virological response).

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/sofosbuvir-velpatasvir/)

## Related drugs

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

## Related conditions

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

[← 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: [DailyMed - SOFOSBUVIR AND VELPATASVIR tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d0c1a945-4440-4b5c-81aa-693ed3db597c) (DailyMed (U.S. National Library of Medicine), 2026); [Hepatitis C](https://www.who.int/news-room/fact-sheets/detail/hepatitis-c) (World Health Organization, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AP55) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025).

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Representative model, for educational purposes only.

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