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Direct-acting antiviral (NS5A + NS3/4A protease inhibitor) Pregnancy: §4.6, verbatim: 'There are no adequate and well-controlled studies with ZEPATIER in pregnant women. Animal studies do not indicate harmful effects with respect to reproductive toxicity. Because reproduction animal studies are not always predictive of human response, ZEPATIER should be used only if the potential benefit justifies the potential risk to the fetus.' Breast-feeding: 'It is unknown whether elbasvir or grazoprevir and their metabolites are excreted in human milk… A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ZEPATIER therapy.' If ZEPATIER is given WITH ribavirin, ribavirin's own contraception, pregnancy-testing, pregnancy and breast-feeding requirements apply — §4.6: 'women of childbearing potential or their male partners must use an effective form of contraception during treatment and for a period of time after the treatment has concluded.'

Elbasvir with grazoprevir

Brand names: Zepatier

Elbasvir with grazoprevir is a fixed-dose direct-acting antiviral combination used to treat chronic hepatitis C virus infection of susceptible genotypes.

Adult dose

Dose: Chronic hepatitis C (CHC) in adults with or without compensated cirrhosis (Child-Pugh A only) — one tablet once daily. §4.2 verbatim: 'The recommended dose is one tablet once daily.' One tablet is elbasvir 50 mg with grazoprevir 100 mg (product name: 'ZEPATIER 50 mg/100 mg film coated tablets'). DURATION BY HCV GENOTYPE, §4.2 Table 1 verbatim: genotype 1a — 'ZEPATIER for 12 weeks', with 'ZEPATIER for 16 weeks plus ribavirin' to be considered 'in patients with baseline HCV RNA level >800,000 IU/mL and/or the presence of specific NS5A polymorphisms causing at least a 5-fold reduction in activity of elbasvir'; genotype 1b — 'ZEPATIER for 12 weeks'; genotype 4 — 'ZEPATIER for 12 weeks', with 'ZEPATIER for 16 weeks plus ribavirin' to be considered 'in patients with baseline HCV RNA level >800,000 IU/mL'. §4.4: 'The efficacy of ZEPATIER has not been demonstrated in HCV genotypes 2, 3, 5 and 6. ZEPATIER is not recommended in patients infected with these genotypes.'
Route: Oral. §4.2 verbatim: 'For oral use. The film-coated tablets should be swallowed whole and may be taken with or without food.' §4.2 also states: 'ZEPATIER treatment should be initiated and monitored by a physician experienced in the management of patients with CHC.'
Frequency: Once daily, for 12 or 16 weeks depending on genotype (see dose). VOMITING, §4.2 verbatim: 'if vomiting occurs within 4 hours of dosing, an additional tablet can be taken up to 8 hours before the next dose. If vomiting occurs more than 4 hours after dosing, no further dose is needed.' MISSED DOSE, §4.2 verbatim: take it 'as soon as possible' if within 16 hours of the usual dosing time and then take the next dose at the usual time; 'If more than 16 hours have passed since ZEPATIER is usually taken, then the patient should be instructed that the missed dose should NOT be taken and to take the next dose per the usual dosing schedule. Patients should be instructed not to take a double dose.'
Max: One tablet (elbasvir 50 mg with grazoprevir 100 mg) once daily. No higher dose appears anywhere in §4.2; the SPC's only ceiling statement is 'Patients should be instructed not to take a double dose', and the sole labelled exception is the replacement tablet after vomiting described under frequency. §4.2 requires NO dose adjustment for the elderly, for mild, moderate or severe renal impairment (including haemodialysis or peritoneal dialysis), or for mild hepatic impairment (Child-Pugh A); moderate or severe hepatic impairment (Child-Pugh B or C) is a contraindication rather than a dose reduction.
THE RIBAVIRIN WEIGHT BANDS IN §4.2 ARE NOT THIS DRUG'S DOSE: the table footnote gives ribavirin's own weight-based dosing for the 16-week combination regimens and directs the reader to ribavirin's own SPC — those milligram figures belong to ribavirin, not to Zepatier, and must never be attached to this page's dose. §4.4: 'The efficacy of ZEPATIER in patients previously exposed to ZEPATIER, or to medicinal products of the same classes… has not been demonstrated.' §4.2: 'The safety and efficacy of ZEPATIER have not been established in liver transplant recipients.'

Paediatric dose

Route: Oral — same route and same fixed-dose tablet as adults.
Frequency: Once daily, in patients 12 years of age and older who weigh at least 30 kg.
Max: One tablet once daily — the same ceiling as adults; the SPC states no separate paediatric maximum.
THIS IS A FIXED-DOSE TABLET, NOT A WEIGHT-BASED DOSE — dosePerKg is deliberately null so that no per-kilogram figure can be multiplied by weight. §4.2 'Paediatric population', verbatim: 'No dosage adjustment of ZEPATIER is required in paediatric patients 12 years of age and older who weigh at least 30 kg (see sections 5.1 and 5.2). The safety and efficacy of ZEPATIER in children aged less than 12 years have not been established.' So for a child of 12 years or over weighing at least 30 kg the dose is the adult one tablet once daily; below 12 years no dose is established. Verify the child's regimen against a current children's formulary before prescribing.

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

  • §4.3, verbatim: 'Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.'
  • §4.3, verbatim: 'Patients with moderate or severe hepatic impairment (Child-Pugh B or C).'
  • §4.3, verbatim: 'Co-administration with inhibitors of organic anion transporting polypeptide 1B (OATP1B), such as rifampicin, atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cobicistat or ciclosporin.'
  • §4.3, verbatim: 'Co-administration with inducers of cytochrome P450 3A (CYP3A) or P-glycoprotein (P-gp), such as efavirenz, phenytoin, carbamazepine, bosentan, etravirine, modafinil or St. John's wort (Hypericum perforatum).'
  • Not a contraindication but a use bar, §4.4: 'ZEPATIER is not recommended in patients infected with' HCV genotypes 2, 3, 5 and 6, in which efficacy has not been demonstrated. §4.4 also states that concomitant use with strong CYP3A inhibitors 'is not recommended'.

Side effects

  • §4.8 summary, verbatim: 'the most commonly reported adverse reactions (greater than 10%) were fatigue and headache. Less than 1 % of subjects treated with ZEPATIER with or without ribavirin had serious adverse reactions (abdominal pain, transient ischaemic attack and anaemia).'
  • Very common (≥1/10): headache, fatigue.
  • Common (≥1/100 to <1/10): decreased appetite; insomnia, anxiety, depression; dizziness; nausea, diarrhoea, constipation, upper abdominal pain, abdominal pain, dry mouth, vomiting; pruritus, alopecia; arthralgia, myalgia; asthenia, irritability.
  • Laboratory (§4.8 Table 4, ZEPATIER 12 weeks without ribavirin, N=834): ALT 5.1–10.0 × ULN (Grade 3) in 6 patients (0.7%) and >10.0 × ULN (Grade 4) in 6 patients (0.7%); total bilirubin 2.6–5.0 × ULN (Grade 3) in 3 patients (0.4%) and >5.0 × ULN in none.
  • INCOMPLETE LIST — §4.8 was cut at the source-fetch limit mid-'Late ALT elevations', so adverse reactions listed beyond that point were never retrieved.

Monitoring

  • §4.4, verbatim: 'Hepatic laboratory testing should be performed prior to therapy, at treatment week 8, and as clinically indicated. For patients receiving 16 weeks of therapy, additional hepatic laboratory testing should be performed at treatment week 12.'
  • §4.4, verbatim: 'Discontinuation of ZEPATIER should be considered if ALT levels are confirmed to be greater than 10 times the ULN. ZEPATIER should be discontinued if ALT elevation is accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or international normalised ratio (INR).'
  • §4.4, verbatim: 'Patients should be instructed to consult their healthcare professional without delay if they have onset of fatigue, weakness, lack of appetite, nausea and vomiting, jaundice or discoloured faeces.'
  • §4.4, hepatitis B, verbatim: 'HBV screening should be performed in all patients before initiation of treatment. HBV/HCV co-infected patients are at risk of HBV reactivation, and should therefore be monitored and managed according to current clinical guidelines.'
  • §4.4 notes higher rates of late ALT elevation in females, Asian patients and subjects aged ≥65 years, generally occurring at or after treatment week 8. §4.4's diabetes paragraph (improved glucose control with possible symptomatic hypoglycaemia) was cut at the source-fetch limit and is incomplete here.

Clinical monograph

How it works

Elbasvir inhibits the HCV NS5A protein essential for viral replication and assembly, while grazoprevir inhibits the NS3/4A protease required for processing of the viral polyprotein.

Prescribing in practice

  • It can cause raised liver transaminases, particularly later in the course, so liver function should be assessed before and during treatment, and it is contraindicated in moderate to severe hepatic impairment.
  • Genotype and baseline resistance-associated substitutions can influence regimen choice and duration, so confirm these before starting.
  • Clinically important drug interactions occur, including with certain statins and other agents, so review concomitant medicines.

Monitoring

Monitor liver function during treatment and confirm cure with HCV RNA testing after completion of the course.

Counselling the patient

  • Take the tablets every day for the full course to give the best chance of clearing the virus.
  • A blood test some weeks after finishing treatment confirms whether the virus has been cleared.

Evidence & guidelines

Use is supported by NICE technology appraisal guidance for chronic hepatitis C and by the registrational direct-acting antiviral trials.

Reference: NICE TA413; EASL HCV; NHS England HCV ODN; SmPC; 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).

Related

Curated clinical cross-links plus same-class fallbacks.

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