[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/hepatitis-c-direct-acting-antivirals/) › Glecaprevir + pibrentasvir [Pharmacology](https://durgical.com/en/pharmacology/) · [Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/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 - Class: [Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/hepatitis-c-direct-acting-antivirals/) - Enzyme: Hepatitis C virus NS3/4A protease (glecaprevir) and NS5A protein (pibrentasvir) - ATC code: J05AP57 - WHO Model List of Essential Medicines ✂**Hepatitis C virus NS3/4A protease (glecaprevir) and NS5A protein (pibrentasvir)**Glecaprevir + pibrentasvir ⓘ The figure shows glecaprevir in the NS3/4A protease domain of hepatitis C genotype 1a; no structure of NS5A with pibrentasvir is available. **Target in 3D:** Hepatitis C virus NS3/4A protease (glecaprevir) and NS5A protein (pibrentasvir). PDB structure 6P6L (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6P6L) · Drag to rotate · pinch to zoom ## 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 →](https://durgical.com/en/conditions/viral-hepatitis/) ## Adverse effects ### Common - Headache - Fatigue and weakness - Nausea and diarrhoea - Itching ### Serious (rare, important) - Hepatitis B reactivation in co-infected people - Liver decompensation in people with advanced cirrhosis ## 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. ## Memory aid GLE-PIB: «Protease + Index (NS5A)», with food, not in decompensated liver. ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/glecaprevir-pibrentasvir/) ## Related drugs - [Sofosbuvir + velpatasvir](https://durgical.com/en/pharmacology/sofosbuvir-velpatasvir/) - [Sofosbuvir](https://durgical.com/en/pharmacology/sofosbuvir/) ## Related conditions - [Viral hepatitis](https://durgical.com/en/conditions/viral-hepatitis/) [← Back to the class: Hepatitis C direct-acting antivirals](https://durgical.com/en/pharmacology/classes/hepatitis-c-direct-acting-antivirals/) 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](https://medlineplus.gov/druginfo/meds/a617039.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Hepatitis C](https://www.who.int/news-room/fact-sheets/detail/hepatitis-c) (World Health Organization, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=J05AP57) (WHO Collaborating Centre for Drug Statistics Methodology, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 63 (McGraw Hill, 2023). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/glecaprevir-pibrentasvir/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/glecaprevir-pibrentasvir/