Pharmacology · Hepatitis C direct-acting antivirals
Glecaprevir + pibrentasvir !
A pangenotypic hepatitis C combination of an NS3/4A protease inhibitor and an NS5A inhibitor, taken with food.
Updated 2026-11-01
The figure shows glecaprevir in the NS3/4A protease domain of hepatitis C genotype 1a; no structure of NS5A with pibrentasvir is available.
Mechanism of action
Glecaprevir blocks the NS3/4A serine protease that cuts the hepatitis C polyprotein into working viral proteins. Pibrentasvir inhibits NS5A, needed for RNA replication and virion assembly. The combination is pangenotypic and active against many strains resistant to older drugs.
- Glecaprevir blocks the NS3/4A protease
- The viral polyprotein is not cut into working proteins
- Pibrentasvir blocks NS5A and the replication complex
- Viral replication stops: cure in most patients
Pharmacokinetics
- Absorption
- Oral, with food; glecaprevir absorption depends on gastric pH
- Metabolism
- Glecaprevir is a CYP3A and OATP1B1/3 substrate; both are P-gp substrates
- Elimination
- Little affected by kidney function: a treatment of choice in chronic kidney disease
Indications
- Chronic hepatitis C of any genotype, including some previously treated patients, in adults and children from 3 years Viral hepatitis →
Adverse effects
Common
- Headache
- Fatigue and weakness
- Nausea and diarrhoea
- Itching
Contraindications
- Decompensated cirrhosis (glecaprevir levels rise sharply in liver impairment)
- Use with atazanavir or rifampicin
Key interactions
- Atazanavir and other HIV protease inhibitors, ciclosporin
- Higher glecaprevir levels and risk of liver injury
- Rifampicin, antiepileptic inducers, efavirenz, St John's wort
- Much lower drug levels; not recommended
- Ethinylestradiol-containing contraceptives
- Raised ALT; not used during and for 2 weeks after treatment
What is monitored
- HBsAg and anti-HBc before starting; liver tests during and after
- Signs of liver decompensation (ascites, jaundice, confusion) in cirrhosis
- Blood glucose in diabetes (it may fall as the liver improves)
- HCV RNA 12 weeks after treatment ends
Administration and safety
- Oral once a day, with food
- Pellets for children are mixed with soft food
- Medicine list reviewed for HIV drugs, statins, anticoagulants and inducers
Nursing care
- Teach to take it with food every day at the same time
- Teach signs of liver problems: jaundice, abdominal swelling, confusion, black stools
- Ask about all prescribed and herbal medicines
- Encourage completing the course
Pregnancy and breastfeeding
Human data are limited; the risk is weighed and pregnancy during treatment is reported to the doctor.
Test yourself
Think of the answer, then tap the question to see it.
Which two viral targets does glecaprevir-pibrentasvir hit?
The NS3/4A protease (glecaprevir) and NS5A (pibrentasvir).
In which patients are hepatitis C protease inhibitors avoided?
In decompensated cirrhosis, where their levels rise many times and liver injury can worsen.
Which HIV drug is contraindicated with this combination?
Atazanavir.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Glecaprevir and Pibrentasvir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Hepatitis C (World Health Organization, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 63 (McGraw Hill, 2023).
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Representative model, for educational purposes only.