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

# Sofosbuvir

The backbone of most hepatitis C regimens. It blocks the virus's RNA polymerase and is always combined with another antiviral.

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 RNA polymerase
- ATC code: J05AP08
- WHO Model List of Essential Medicines

✂**Hepatitis C virus NS5B RNA polymerase**Sofosbuvir

ⓘ The figure shows the active diphosphate-level metabolite of sofosbuvir bound to the hepatitis C NS5B polymerase (genotype 2a) with RNA.

**Target in 3D:** Hepatitis C virus NS5B RNA polymerase. 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

Sofosbuvir is a phosphoramidate prodrug of a uridine nucleotide. In liver cells it is converted to the active triphosphate (GS-461203), which competes with uridine triphosphate and is built into the new viral RNA by NS5B; once incorporated it stops chain growth. Its high barrier to resistance makes it a good partner for NS5A or protease inhibitors.

- Taken up by liver cells and converted to the active triphosphate
- Competes with UTP at the NS5B polymerase
- Incorporated into viral RNA, it stops the chain
- Combined with another antiviral, it cures most infections

## Pharmacokinetics

**Absorption**
Oral

**Metabolism**
Activated in the liver; dephosphorylated to the inactive metabolite GS-331007

**Elimination**
GS-331007 mainly by the kidneys

## Indications

- Chronic hepatitis C, always with other antivirals (NS5A inhibitors such as daclatasvir, velpatasvir or ledipasvir, or ribavirin) [Viral hepatitis →](https://durgical.com/en/conditions/viral-hepatitis/)

## Adverse effects

### Common

- Headache and fatigue
- Insomnia and irritability
- Nausea and diarrhoea
- Itching and rash

### Serious (rare, important)

- Reactivation of hepatitis B in co-infected people, with possible liver failure
- Severe symptomatic bradycardia with amiodarone
- Anaemia when combined with ribavirin

## Contraindications

- Contraindications of the partner drug apply (for example pregnancy when given with ribavirin)
- Use with amiodarone is not recommended

## Key interactions

**Amiodarone**
Severe, even fatal, bradycardia and cardiac arrest

**St John's wort, rifampicin, carbamazepine and phenytoin (P-gp inducers)**
Lower sofosbuvir levels and risk of treatment failure

## What is monitored

- Hepatitis B tests (HBsAg, anti-HBc) before starting
- Liver tests during and after treatment
- HCV RNA at the end of treatment and 12 weeks later (cure)
- Heart rate if amiodarone was used recently

## Administration and safety

- Oral once daily
- Always part of a combination; never given alone
- Medicine list reviewed for amiodarone and inducers before starting

## Nursing care

- Ask about all medicines and herbal products, especially amiodarone and St John's wort
- Teach to report dizziness, fainting, chest pain or breathlessness
- Teach to report jaundice, dark urine or pale stools
- Encourage completing the full course

## Pregnancy and breastfeeding

Human data are limited; when combined with ribavirin, pregnancy must be avoided and tested for.

## Memory aid

SoFosbUvir = Uridine in disguise for NS5B; «Sofos-BRADY» with amiodarone.

## Test yourself

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

## Which hepatitis C protein does sofosbuvir inhibit?

The NS5B RNA-dependent RNA polymerase.

## Which antiarrhythmic causes dangerous bradycardia with sofosbuvir?

Amiodarone.

## Why is hepatitis B tested before sofosbuvir-based treatment?

Hepatitis B can reactivate as hepatitis C is cleared, sometimes causing liver failure.

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

## Related drugs

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

[← 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: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a614014.html) (MedlinePlus (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=J05AP08) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 63 (McGraw Hill, 2023).

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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/