Antiviral — Hepatitis C (Pan-Genotypic DAA) Pregnancy: Sofosbuvir: avoid — insufficient human data. Ribavirin (when co-administered for decompensated cirrhosis): absolutely contraindicated in pregnancy (highly teratogenic). Highly effective contraception mandatory if ribavirin used.

Sofosbuvir / Velpatasvir

Brand names: Epclusa

Adult dose

Dose: 1 tablet (sofosbuvir 400 mg / velpatasvir 100 mg) once daily with or without food

Route: Oral

Frequency: Once daily

Max: 400/100 mg once daily

All HCV genotypes 1–6. Non-cirrhotic and compensated cirrhotic (Child-Pugh A): 12 weeks. Decompensated cirrhosis (Child-Pugh B/C): 12 weeks with ribavirin. Without ribavirin in decompensated cirrhosis only if ribavirin intolerant. Source: BNF 90; EASL HCV Guidelines 2022.

Paediatric dose

Dose: Oral pellets available for children ≥3 years: weight 17–30 kg: sofosbuvir 200 mg/velpatasvir 50 mg once daily; >30 kg: adult tablet See weight bands/kg

Route: Oral (pellets mixed with food for young children)

Frequency: Once daily

Max: 400/100 mg/day

Paediatric pellet formulation: sprinkle on soft food (applesauce, pudding) — do not crush tablet. Source: BNF for Children 2024; EASL.

Dose adjustments

Renal

eGFR ≥30 mL/min: no adjustment. eGFR <30 mL/min: use with caution — sofosbuvir GS-331007 metabolite accumulates (renal clearance). Haemodialysis: not recommended (sofosbuvir AUC increases 20-fold). Consider glecaprevir/pibrentasvir in severe CKD.

Hepatic

Compensated cirrhosis (Child-Pugh A): standard 12-week course. Decompensated cirrhosis (Child-Pugh B/C): sofosbuvir/velpatasvir + ribavirin for 12 weeks — ONLY pan-genotypic DAA safe and recommended in decompensated cirrhosis.

Paediatric weight-based calculator

Patient weight (kg)

Paediatric pellet formulation: sprinkle on soft food (applesauce, pudding) — do not crush tablet. Source: BNF for Children 2024; EASL.

Clinical pearls

ONLY DAA approved for decompensated cirrhosis: sofosbuvir/velpatasvir (with ribavirin) is the ONLY pan-genotypic direct-acting antiviral regimen proven safe and effective in Child-Pugh B/C decompensated cirrhosis. All other regimens (glecaprevir/pibrentasvir, sofosbuvir/ledipasvir) are contraindicated in Child-Pugh B/C.
MHRA 2015 amiodarone warning: fatal bradycardia and heart block reported when sofosbuvir started in patients taking amiodarone (and amiodarone + beta-blocker combinations). Mechanism unclear. MHRA requires: if concurrent use unavoidable, admit for cardiac monitoring for 48 hours after starting HCV treatment; thereafter self-monitor daily pulse for 2 weeks and attend ED urgently if pulse slows.
PPI interaction — clinical management: velpatasvir is a weak base requiring gastric acid for solubility. PPIs reduce velpatasvir AUC 50–75%. If PPI needed: use lowest dose (omeprazole max 20 mg), take 4 hours BEFORE sofosbuvir/velpatasvir dose, ensure meal taken with tablet. Consider H2-blocker as alternative.
POLARIS trials: SVR12 >95% across all genotypes (1–6) including compensated and decompensated cirrhosis. Particularly important for genotype 3 (historically difficult to treat).
HBV reactivation risk — same as all DAAs: mandatory HBsAg/anti-HBc screen before starting. If HBsAg positive, initiate entecavir or tenofovir before or at the same time as HCV DAA. MHRA black box warning. Source: BNF 90; EASL HCV 2022; MHRA Drug Safety Update 2015 (amiodarone).

Contraindications

Rifampicin and strong P-gp/CYP inducers: reduce sofosbuvir/velpatasvir levels — contraindicated
HBV co-infection without suppressive therapy — HBV reactivation risk (MHRA warning)
Severe renal impairment (eGFR <30 mL/min) — accumulation of sofosbuvir metabolite

Side effects

Headache, fatigue, nausea (mild — similar to placebo in trials)
Anaemia (if ribavirin co-administered — ribavirin causes haemolytic anaemia)
Bradycardia and heart block — MHRA 2015 WARNING (see pearls)
HBV reactivation (MHRA black box warning — same as all DAAs)
Photosensitivity (rare — velpatasvir)

Interactions

Amiodarone (alone or with other antiarrhythmics): MHRA 2015 warning — severe symptomatic bradycardia and fatal heart block reported with sofosbuvir-based regimens. Avoid combination; if unavoidable, cardiac monitoring in hospital for 48 hours after starting HCV treatment
Proton pump inhibitors: reduce velpatasvir levels (require high gastric pH for absorption). Omeprazole max 20 mg/day if needed — separate dosing (take Epclusa with food, PPI 4 hours before). Avoid high-dose PPIs
Rifampicin, carbamazepine, St John's Wort, phenytoin: P-gp/CYP inducers — contraindicated
Rosuvastatin: velpatasvir increases rosuvastatin exposure 2.7-fold — reduce statin dose
Ciclosporin: increased velpatasvir concentrations — monitor
HBV: reactivation MHRA black box — screen pre-treatment

Monitoring

HCV RNA at end of treatment and SVR12
HBsAg and anti-HBc pre-treatment
Full blood count if ribavirin co-administered (haemolytic anaemia monitoring)
Cardiac monitoring if amiodarone used concomitantly
Liver function tests (Child-Pugh scoring in decompensated cirrhosis)
Renal function (eGFR) — especially with ribavirin and in renal impairment

Reference: BNFc; BNF 90; EASL HCV Recommendations 2022; Foster et al. NEJM 2015 (ASTRAL-3 genotype 3); MHRA Drug Safety Update Nov 2015 (amiodarone). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Drugs

Glecaprevir / Pibrentasvir · Antiviral — Hepatitis C (Pan-Genotypic DAA)

Pathways