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# Ledipasvir + sofosbuvir

A single-tablet hepatitis C combination for genotypes 1, 4, 5 and 6. It joins an NS5A inhibitor with the NS5B inhibitor sofosbuvir.

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 NS5A protein (ledipasvir) and NS5B polymerase (sofosbuvir)
- ATC code: J05AP51
- WHO Model List of Essential Medicines

✂**Hepatitis C virus NS5A protein (ledipasvir) and NS5B polymerase (sofosbuvir)**Ledipasvir + sofosbuvir

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

**Target in 3D:** Hepatitis C virus NS5A protein (ledipasvir) and NS5B polymerase (sofosbuvir). 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

Ledipasvir inhibits NS5A, a protein needed for viral RNA replication and virion assembly. Sofosbuvir is converted to a uridine triphosphate analogue that NS5B incorporates into viral RNA, stopping the chain. The two together suppress replication strongly and prevent resistance.

- Ledipasvir blocks NS5A
- Sofosbuvir triphosphate stops RNA synthesis by NS5B
- Replication and assembly fail
- Most infections with genotypes 1, 4, 5 and 6 are cured

## Pharmacokinetics

**Absorption**
Oral; ledipasvir dissolves less as gastric pH rises

**Elimination**
Ledipasvir mostly unchanged in the faeces through the bile; sofosbuvir metabolite GS-331007 in the urine

**Half-life**
Ledipasvir about 47 hours

## Indications

- Chronic hepatitis C genotypes 1, 4, 5 and 6 in adults and children from 3 years (with ribavirin in some situations, such as decompensated cirrhosis) [Viral hepatitis →](https://durgical.com/en/conditions/viral-hepatitis/)

## Adverse effects

### Common

- Fatigue
- Headache
- Weakness

### Serious (rare, important)

- Hepatitis B reactivation in co-infected people
- Severe, sometimes fatal, bradycardia with amiodarone

## Contraindications

- When combined with ribavirin, the contraindications of ribavirin apply

## Key interactions

**Antacids**
Separated by at least 4 hours

**H2 blockers and proton pump inhibitors**
Lower ledipasvir absorption; only limited doses are allowed

**Rifampicin and St John's wort (P-gp inducers)**
Lower drug levels; not recommended

**Rosuvastatin**
Higher statin levels; not recommended

**Amiodarone**
Severe bradycardia

## What is monitored

- HBsAg and anti-HBc before starting; liver tests during and after
- HCV RNA 12 weeks after treatment ends
- Kidney function with tenofovir-containing HIV regimens

## Administration and safety

- One tablet a day
- Medicine list reviewed for acid-reducing drugs, statins, inducers and amiodarone

## Nursing care

- Ask about over-the-counter antacids and stomach-acid medicines
- Teach to report slow pulse or fainting
- Encourage completing the course

## Pregnancy and breastfeeding

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

## Memory aid

LEDipasvir «LEaDs» NS5A; avoid acid blockers (it needs acid).

## Test yourself

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

## Which genotypes does ledipasvir-sofosbuvir cover?

Genotypes 1, 4, 5 and 6 (not pangenotypic).

## How is ledipasvir mainly eliminated?

Unchanged in the faeces through the bile.

## Why are proton pump inhibitors limited with ledipasvir?

Ledipasvir dissolves less at higher gastric pH, so absorption falls.

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## Related drugs

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

## 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: [DailyMed - LEDIPASVIR AND SOFOSBUVIR tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f4a73b-0cd6-4902-9092-3ac79e882c1a) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AP51) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); [eEML - Electronic Essential Medicines List](https://list.essentialmeds.org/) (World Health Organization, 2025); 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/ledipasvir-sofosbuvir/