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Antiviral — Hepatitis C (Pan-Genotypic DAA) Pregnancy: Avoid — insufficient human data. No reproductive studies. Use only if clearly necessary with specialist input.

Glecaprevir / Pibrentasvir

Brand names: Maviret

Adult dose

Dose: 3 tablets (glecaprevir 100 mg / pibrentasvir 40 mg per tablet) once daily with food
Route: Oral
Frequency: Once daily with food
Max: 3 tablets (300/120 mg) once daily
Treatment-naïve, no cirrhosis: 8 weeks (all genotypes 1–6). Treatment-naïve, compensated cirrhosis: 12 weeks. Prior NS5A or NS3/4A treatment: 12–16 weeks depending on genotype and prior treatment history. Must be taken with food — fat improves glecaprevir absorption 83–163%. Source: BNF 90; EASL HCV Guidelines 2022.

Paediatric dose

Dose: Not weight-based — paediatric dosing by age: ≥12 years: 3 tablets (adult dose); 6–11 years: granules/paediatric formulation — specialist prescribing only tablets/kg
Route: Oral
Frequency: Once daily with food
Max: 3 tablets/day
Licensed from 3 years (granule formulation) in US — UK licensing for ≥12 years tablets. Paediatric use under specialist hepatology guidance. Source: BNF for Children 2024.

Dose adjustments

Renal

No dose adjustment required at any level of renal impairment including haemodialysis — key advantage over sofosbuvir-based regimens (sofosbuvir requires eGFR >30 mL/min).

Hepatic

Compensated cirrhosis (Child-Pugh A): safe — use 12-week course. Decompensated cirrhosis (Child-Pugh B/C): CONTRAINDICATED — increases risk of serious hepatotoxicity and HBV reactivation without adequate benefit.

Paediatric weight-based calculator

Licensed from 3 years (granule formulation) in US — UK licensing for ≥12 years tablets. Paediatric use under specialist hepatology guidance. Source: BNF for Children 2024.

Clinical pearls

  • 8-week pan-genotypic cure: first-line for treatment-naïve non-cirrhotic patients of any HCV genotype (1–6). Sustained virological response (SVR12) >97% in clinical trials. ENDURANCE trials and EXPEDITION programme.
  • HBV reactivation — MHRA black box warning: all direct-acting antivirals (DAAs) including glecaprevir/pibrentasvir carry MHRA warning for HBV reactivation in HBV co-infected patients. MANDATORY: test all HCV patients for HBsAg, anti-HBc before starting. If HBsAg positive — initiate HBV treatment before or concomitantly with HCV DAA.
  • CKD/dialysis advantage: unlike sofosbuvir-based regimens (require eGFR >30 mL/min), glecaprevir/pibrentasvir is safe at any eGFR including dialysis — first-choice for HCV in advanced CKD or on haemodialysis.
  • Decompensated cirrhosis is an absolute CI: sofosbuvir/velpatasvir (+/- voxilaprevir) is the ONLY DAA approved for decompensated cirrhosis. Glecaprevir/pibrentasvir is hepatotoxic in Child-Pugh B/C.
  • Statin interactions require management: pibrentasvir inhibits OATP1B1/3 transporters — statins using these transporters (rosuvastatin, atorvastatin) accumulate dangerously. Manage: dose cap rosuvastatin to 10 mg, switch to fluvastatin or pravastatin where possible. Source: BNF 90; EASL HCV Guidelines 2022; MHRA SPC Maviret.

Contraindications

  • Decompensated cirrhosis (Child-Pugh B or C) — contraindicated
  • Rifampicin and other strong P-gp/CYP3A inducers: contraindicated — dramatically reduce glecaprevir levels
  • Atazanavir: contraindicated — increases glecaprevir/pibrentasvir levels to potentially toxic concentrations
  • HBV co-infection without suppressive HBV therapy — HBV reactivation MHRA black box warning

Side effects

  • Headache, fatigue (most common ~15%)
  • Nausea, diarrhoea
  • Pruritus
  • Elevated bilirubin (pibrentasvir — usually indirect, benign)
  • HBV reactivation (serious — MHRA black box warning; see pearls)

Interactions

  • Rifampicin and rifabutin: strong P-gp/CYP3A4 inducers — contraindicated (reduce glecaprevir plasma concentration by >80%)
  • Atazanavir: NS3/4A protease inhibitor — additive NS3 inhibition + P-gp inhibition: contraindicated — 6-fold increase in glecaprevir AUC
  • Ciclosporin doses >100 mg/day: increases glecaprevir 15-fold — contraindicated at high doses
  • Statins (rosuvastatin, atorvastatin, simvastatin): pibrentasvir inhibits OATP1B1/3 and BCRP — significant statin exposure increases. Rosuvastatin: max 10 mg; pravastatin: max 40 mg; avoid simvastatin/lovastatin
  • Dabigatran, digoxin: P-gp substrate interactions — monitor
  • Oral contraceptives (ethinylestradiol-containing): avoid — increased ALT risk (not related to contraceptive efficacy)

Monitoring

  • HCV RNA at end of treatment and SVR12 (12 weeks post-treatment) — undetectable confirms cure
  • HBsAg and anti-HBc before starting (HBV co-infection screen)
  • Liver function tests at baseline and end of treatment
  • Statin levels (clinical monitoring — myopathy symptoms if concurrent statin)
  • Bilirubin (mild rise expected — indirect, usually benign)

Reference: BNFc; BNF 90; EASL Recommendations on Treatment of Hepatitis C 2022; MHRA SPC Maviret; Zeuzem et al. NEJM 2018 (ENDURANCE-1). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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