Velpatasvir

Velpatasvir is an oral pangenotypic hepatitis C NS5A inhibitor available in a fixed-dose tablet with sofosbuvir. It gives cure rates over 95% across all genotypes after 12 weeks and is the usual single-tablet regimen where no genotype test is available. Acid suppression and enzyme inducers lower its levels.

Class. Direct-acting antiviral; NS5A inhibitor.

Mechanism. Binds the viral NS5A protein and blocks RNA replication and virion assembly across genotypes 1 to 6.

Pharmacokinetics. Absorption falls with raised gastric pH. Half life about 15 hours. Metabolised by CYP2B6, CYP2C8 and CYP3A4. A P-glycoprotein and BCRP substrate.

Chronic hepatitis C, all genotypes (adults). - One tablet orally once daily containing sofosbuvir 400 mg and velpatasvir 100 mg for 12 weeks. - Decompensated cirrhosis: add ribavirin (1000 mg daily under 75 kg; 1200 mg daily at 75 kg or more) for 12 weeks, or give 24 weeks without ribavirin if ribavirin cannot be used.

Children 3 years and over. Weight-banded: under 17 kg 150/37.5 mg; 17 to under 30 kg 200/50 mg; 30 kg or more 400/100 mg once daily.

Loading dose, maintenance dose and titration. Not applicable. Maximum: one tablet daily.

Main alternative. Glecaprevir with pibrentasvir.

Contraindications. Hypersensitivity; co-administration with rifampicin, rifapentine, carbamazepine, phenytoin, phenobarbital, St John’s wort, and efavirenz.

Serious adverse effects. Hepatitis B reactivation, symptomatic bradycardia with amiodarone, and hepatic decompensation in advanced cirrhosis.

Common adverse effects. Headache, fatigue, nausea and insomnia.

Interactions. - Proton pump inhibitors: avoid, or give omeprazole 20 mg 4 hours after velpatasvir with food. - H2 blockers: at the same time or 12 hours apart; antacids 4 hours apart. - Tenofovir disoproxil fumarate with boosted regimens raises tenofovir exposure; monitor kidney function. - Amiodarone: avoid.

Common prescribing errors. Using a proton pump inhibitor, treating with efavirenz or rifampicin, and omitting a hepatitis B check.

Special groups. - Pregnancy: limited data; use only when needed. - Breastfeeding: limited data. - Children: weight-banded from 3 years. - Older adults: usual dose. - Kidney impairment: usual dose. - Liver impairment: usual dose in compensated disease; add ribavirin in decompensated disease under specialist care.

Regional points. The pangenotypic tablet avoids the need for genotyping, which is rarely available; hepatitis B and HIV co-infection testing before treatment changes the regimen.

Formulations. Fixed-dose tablet 400/100 mg; lower-strength tablets and granules for children.

Administration. Once daily with or without food.

Baseline. HCV RNA, hepatitis B surface antigen and core antibody, HIV test, fibrosis assessment, creatinine, pregnancy test.

Monitoring. ALT at 4 weeks; HCV RNA 12 weeks after treatment; haemoglobin if ribavirin is used.

Stopping thresholds. Stop for jaundice, hepatic decompensation, or ALT over 3 times the upper limit of normal with symptoms, or over 5 times without.

Referral and escalation. Specialist review for decompensated cirrhosis, co-infection and failure.