Pan-genotypic DAA salvage combination Pregnancy: eMC §4.6: there are no or limited data (fewer than 300 pregnancy outcomes) from use in pregnant women. Animal studies do not indicate reproductive toxicity for sofosbuvir or voxilaprevir, but animal studies have shown a possible link to reproductive toxicity for velpatasvir. As a precautionary measure, use is NOT RECOMMENDED during pregnancy. Breast-feeding: it is unknown whether sofosbuvir, its metabolites, velpatasvir or voxilaprevir are excreted in human milk; animal data show excretion of velpatasvir and sofosbuvir metabolites in milk and voxilaprevir was detected in the plasma of nursing pups, so a risk to the newborn/infant cannot be excluded and it should NOT be used during breast-feeding. Fertility: no human data; animal studies do not indicate harmful effects.

Sofosbuvir with velpatasvir and voxilaprevir

Brand names: Vosevi

An oral pan-genotypic direct-acting antiviral fixed triple combination (marketed as Vosevi) used to treat chronic hepatitis C, particularly as a salvage regimen in patients who have failed previous direct-acting antiviral therapy.

Adult dose

Dose: One 400 mg/100 mg/100 mg tablet (or two 200 mg/50 mg/50 mg tablets) once daily

Route: Oral, with food. Swallow the tablet(s) whole; because of the bitter taste it is recommended that the film-coated tablet is not chewed or crushed.

Frequency: Once daily. Duration by patient population: DAA-naive without cirrhosis 8 weeks; DAA-naive with compensated cirrhosis 12 weeks (8 weeks may be considered in genotype 3 infected patients); DAA-experienced without cirrhosis or with compensated cirrhosis 12 weeks

eMC §4.2 (Sofosbuvir/Velpatasvir/Voxilaprevir Gilead 400 mg/100 mg/100 mg film-coated tablets, previously known as Vosevi). Treatment should be initiated and monitored by a physician experienced in the management of patients with HCV infection. The stated dose applies to patients aged 12 years and older and weighing at least 30 kg, and the treatment durations above apply to all HCV genotypes. In the clinical studies the DAA-experienced patients had been exposed to combination regimens containing any of: daclatasvir, dasabuvir, elbasvir, grazoprevir, ledipasvir, ombitasvir, paritaprevir, sofosbuvir, velpatasvir, or voxilaprevir (administered with sofosbuvir and velpatasvir for less than 12 weeks). MISSED DOSE: if within 18 hours of the normal time, take the tablet(s) as soon as possible and take the next dose at the usual time; if after 18 hours, wait and take the next dose at the usual time. Never take a double dose. VOMITING: if vomiting occurs within 4 hours of dosing an additional dose should be taken; if more than 4 hours after dosing, no further dose is needed. ELDERLY: no dose adjustment warranted. HEPATIC IMPAIRMENT: no dose adjustment for mild impairment (Child-Pugh-Turcotte Class A); NOT RECOMMENDED in moderate or severe hepatic impairment (CPT Class B or C). LIVER TRANSPLANT: safety and efficacy post-liver transplant have not been assessed; treatment should be guided by an assessment of the potential benefits and risks for the individual patient. §4.4: HBV screening should be performed in all patients before initiation of treatment, as cases of HBV reactivation, some fatal, have been reported during or after treatment with DAAs, and there are no data on use in HCV/HBV co-infection. PAEDIATRIC: the dose above covers patients aged 12 years and older weighing at least 30 kg; safety and efficacy in children aged under 12 years and weighing under 30 kg have not yet been established and no data are available. This is a fixed adult-strength dose, not a per-kg dose - verify all under-18 dosing against a children's formulary.

Dose adjustments

Renal

eMC §4.2: no dose adjustment is required for mild or moderate renal impairment. Safety data are limited in severe renal impairment (eGFR under 30 mL/min/1.73 m2) and end stage renal disease requiring haemodialysis, and the product has not been studied in ESRD requiring dialysis; it can be used in these patients with no dose adjustment when no other relevant treatment options are available.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients (§4.3)
Concomitant use with medicinal products that are strong P-glycoprotein (P-gp) and/or strong cytochrome P450 (CYP) inducers, e.g. carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin and St John's wort (§4.3)
Concomitant use with rosuvastatin or dabigatran etexilate (§4.3)
Concomitant use with ethinylestradiol-containing medicinal products such as combined oral contraceptives, contraceptive vaginal rings or transdermal patches (§4.3)

Side effects

Very common: headache; diarrhoea; nausea
Common: abdominal pain, decreased appetite, vomiting
Common: rash; myalgia. Uncommon: angioedema (post-marketing for sofosbuvir/velpatasvir-containing products); muscle spasm
Common: total bilirubin increased - in the Phase 3 studies increases of up to 1.5 times the upper limit of normal were observed in 4% of patients without cirrhosis and 10% of patients with compensated cirrhosis, due to inhibition of OATP1B1 and OATP1B3 by voxilaprevir; levels decreased after completing treatment
Frequency not known: Stevens-Johnson syndrome. Post-marketing: severe bradycardia and heart block when sofosbuvir-containing regimens are used with amiodarone and/or other heart-rate-lowering medicinal products

Interactions

Strong P-gp and/or strong CYP inducers (carbamazepine, phenobarbital, phenytoin, rifampicin, rifabutin, St John's wort) - contraindicated (§4.3)
Rosuvastatin and dabigatran etexilate - contraindicated (§4.3)
Ethinylestradiol-containing products (combined oral contraceptives, vaginal rings, transdermal patches) - contraindicated (§4.3)
Amiodarone (§4.4) - life-threatening cases of severe bradycardia and heart block have been observed when sofosbuvir-containing regimens are used with amiodarone, generally within hours to days but up to about 2 weeks after starting HCV treatment. Amiodarone should only be used when alternative antiarrhythmics are not tolerated or are contraindicated; if concomitant use is necessary, monitor cardiac rhythm as an in-patient for the first 48 hours then daily heart-rate self-monitoring for at least the first 2 weeks; the same applies to patients who discontinued amiodarone within the past few months because of its long half-life
Other medicinal products that lower heart rate (§4.8) - also associated with severe bradycardia and heart block in combination with sofosbuvir-containing regimens
Moderate P-gp inducers or moderate CYP inducers - §4.4 contains a caution on use with these, but the text was truncated in this bundle; the eMC §4.5 interaction section was not captured - clinician to review the full SPC interaction table

Clinical monograph

How it works

Sofosbuvir inhibits the NS5B polymerase, velpatasvir inhibits the NS5A protein, and voxilaprevir inhibits the NS3/4A protease — three complementary targets that provide a high barrier to resistance for treatment-experienced infection.

Prescribing in practice

Co-administration with amiodarone risks serious symptomatic bradycardia and should generally be avoided; review for this and other significant interactions before starting.
The voxilaprevir protease-inhibitor component means it is not recommended in moderate-to-severe hepatic impairment (decompensated cirrhosis), and acid-suppressing drugs and potent enzyme inducers can reduce efficacy.
Screen for hepatitis B before treatment owing to the risk of HBV reactivation during HCV direct-acting antiviral therapy.

Monitoring

Monitor HCV viral load to confirm response and assess hepatic function, reserving this regimen for appropriate compensated liver disease and watching for hepatitis B reactivation.

Counselling the patient

Take one tablet once daily with food for the full prescribed course.
Share a complete list of your medicines, including indigestion remedies and herbal products such as St John's wort.
Report any fainting or very slow heartbeat, especially if you take medicines for heart rhythm.

Evidence & guidelines

Sofosbuvir with velpatasvir and voxilaprevir is recommended by NICE as a salvage regimen for chronic hepatitis C in patients previously treated with direct-acting antivirals, supported by the POLARIS trials.

Reference: NICE TA507; EASL; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways