Pharmacology · 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
The figure shows the active diphosphate-level metabolite of sofosbuvir bound to the hepatitis C NS5B polymerase (genotype 2a) with RNA.
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 →
Adverse effects
Common
- Headache and fatigue
- Insomnia and irritability
- Nausea and diarrhoea
- Itching and rash
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.
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.
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: Sofosbuvir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Hepatitis C (World Health Organization, 2026); ATCDDD - ATC/DDD Index (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.