Sofosbuvir + velpatasvir + voxilaprevir
Hepatitis C direct-acting antivirals
Hepatitis C direct-acting antivirals
A three-drug hepatitis C tablet for people whose earlier direct-acting antiviral treatment failed. It covers all genotypes.
Quick facts
- Group
- Hepatitis C direct-acting antivirals
- Target
- HCV NS5B polymerase (sofosbuvir), NS5A (velpatasvir) and NS3/4A protease (voxilaprevir)
- Used for
- Chronic hepatitis C
- Key effects
- Headache · Tiredness · Diarrhoea
- Monitor
- HBsAg and anti-HBc before starting · Liver enzymes
- ATC
- J05AP56
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows voxilaprevir in the active site of the HCV NS3/4A protease, one of the three targets.
The tablet blocks three viral steps at once. Sofosbuvir is a nucleotide prodrug whose triphosphate is built into the viral RNA by the NS5B polymerase and stops chain growth. Velpatasvir inhibits NS5A, needed for replication and assembly. Voxilaprevir blocks the NS3/4A protease that cuts the viral polyprotein. Three targets make the combination effective even after failure of an NS5A-containing regimen.
- Sofosbuvir stops RNA synthesis by NS5B
- Velpatasvir blocks NS5A replication and assembly
- Voxilaprevir blocks the NS3/4A protease
- Three targets overcome earlier resistance
Indications
- Chronic hepatitis C, all genotypes, in adults previously treated with a direct-acting antiviral regimen (retreatment) Viral hepatitis →
Adverse effects
Common
- Headache
- Tiredness
- Diarrhoea
- Nausea
- Insomnia and low mood
Contraindications
- Rifampicin (and other strong inducers of P-gp or CYP3A)
- Moderate or severe hepatic impairment (decompensated cirrhosis)
Key interactions
- Amiodarone
- Severe, sometimes fatal bradycardia with sofosbuvir; avoided or closely monitored
- Ciclosporin (strong OATP1B1 inhibitor)
- Raises voxilaprevir; not combined
- Rosuvastatin, methotrexate and other BCRP substrates
- Voxilaprevir raises their levels; avoided
- Antacids with aluminium or magnesium
- Lower velpatasvir absorption; doses are separated in time
What is monitored
- HBsAg and anti-HBc before starting
- Heart rate if amiodarone was used recently
- Liver enzymes
- HCV RNA after treatment
Administration and safety
- One tablet by mouth with food
- Antacids are separated from the tablet by several hours
- The full course is completed even when the person feels well
Pregnancy and breastfeeding
Safety in pregnancy is not established; benefit and risk are weighed.
Nursing care
- Review cardiac drugs, especially amiodarone, before starting
- Check hepatitis B status
- Teach to report fainting, slow pulse or breathlessness
- Teach to report jaundice, abdominal swelling or black stools
Pharmacokinetics
- Absorption
- Oral, with food (food raises voxilaprevir exposure)
- Metabolism
- Voxilaprevir is a substrate of CYP3A4, CYP2C8, CYP1A2, P-gp, BCRP and OATP1B1/3, and inhibits P-gp, BCRP and OATP1B1/3
- Elimination
- Voxilaprevir mainly in bile and faeces
Test yourself
Think of the answer, then tap the question to see it.
When is sofosbuvir + velpatasvir + voxilaprevir used?
For retreatment of chronic hepatitis C after failure of an earlier direct-acting antiviral regimen.
Which drug in the tablet blocks the NS3/4A protease?
Voxilaprevir.
Which heart drug is dangerous with sofosbuvir-containing regimens?
Amiodarone, because of severe bradycardia.
Connections
← Back to the class: 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, Velpatasvir, and Voxilaprevir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Crystal structure of HCV NS3/4A protease in complex with voxilaprevir (RCSB Protein Data Bank, 2019).
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Representative model, for educational purposes only.