Pharmacology · Hepatitis C direct-acting antivirals
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
The figure shows the active diphosphate-level metabolite of sofosbuvir in the hepatitis C NS5B polymerase; no structure of NS5A with ledipasvir is available.
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 →
Adverse effects
Common
- Fatigue
- Headache
- Weakness
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.
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.
Related drugs
Related conditions
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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 (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (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.