Elbasvir
Identification
- Summary
Elbasvir is an antiviral and NS5A inhibitor used to treat hepatitis C infections.
- Brand Names
- Zepatier
- Generic Name
- Elbasvir
- DrugBank Accession Number
- DB11574
- Background
Elbasvir is a direct-acting antiviral medication used as part of combination therapy to treat chronic hepatitis C, an infectious liver disease caused by infection with hepatitis C virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, affecting 72% of all chronic HCV patients.6 Treatment options for chronic hepatitis C have advanced significantly since 2011, with the development of direct-acting antivirals (DAAs) such as elbasvir. Elbasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly.Synthesis The barrier to the development of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs.3 Substitutions at amino acid positions 28, 30, 31, or 93 are known to confer resistance to elbasvir.7 Despite this disadvantage elbasvir is still effective against HCV, particularly when paired with grazoprevir.
Elbasvir is available as a fixed-dose combination product with grazoprevir (tradename: Zepatier) used for the treatment of chronic hepatitis C. Approved in January 2016 by the FDA, Zepatier is indicated for the treatment of HCV genotypes 1 and 4 with or without ribavirin depending on the presence of resistance-associated amino acid substitutions in the NS5A protein and previous treatment failure with ribavirin, peginterferon alfa-2a, peginterferon alfa-2b, or other NS3/4A inhibitors like boceprevir, simeprevir, or telaprevir.7 Elbasvir and grazoprevir are used with or without ribavirin with the intent to cure, or achieve a sustained virologic response (SVR), and have been shown to achieve a SVR between 94% and 97% for genotype 1 and 97% and 100% for genotype 4 after 12 weeks of treatment.6. SVR and eradication of HCV infection are associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of hepatocellular carcinoma, and reduced all-cause mortality.4
In a computational target-based drug repurposing investigation published in April 2020, elbasvir was predicted to bind stably and preferentially to three proteins necessary for viral replication of SARS-CoV-2, the human coronavirus responsible for the COVID-19 pandemic.5 While these results are suggestive of antiviral efficacy, follow-up clinical trials are required to validate elbasvir as a potential therapy against SARS-CoV-2.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Elbasvir (DB11574)
- Weight
- Average: 882.035
Monoisotopic: 881.422445147 - Chemical Formula
- C49H55N9O7
- Synonyms
- Elbasvir
- External IDs
- MK 8742
- MK-8742
- MK8742
Pharmacology
- Indication
Elbasvir, when used in combination with grazoprevir as the combination product Zepatier, is indicated for use with or without ribavirin for the treatment of chronic HCV genotypes 1 or 4 infection in adults.7
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- Contraindications & Blackbox Warnings
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Elbasvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4.7
- Mechanism of action
Elbasvir is an inhibitor of the HCV non-structural protein 5A. While the precise role of this protein is unknown, it is essential to viral replication and virion assembly.Synthesis Potential modes of action of NS5A inhibitors like elbasvir include blocking signaling interactions, redistribution of NS5A from the endoplasmic reticulum to the surface of lipid droplets, and modification of the HCV replication complex.3
Computational target-based in silico research suggests that elbasvir may carry activity at several proteins required for replication of SARS-CoV-2 - namely RNA-dependent RNA polymerase, helicase, and papain-like proteinase - although specific activity has yet to be affirmed by follow-up clinical studies.5
Target Actions Organism ANonstructural protein 5A inhibitorHepatitis C Virus - Absorption
Elbasvir reaches peak plasma concentration 3-6 hours after administration7 and has an absolute bioavailability of 32%. When co-administered with food, the peak concentration of elbasvir increases 1.5-fold, but this increase in exposure is not likely to be clinically relevant.
- Volume of distribution
Elbasvir has an estimated apparent volume of distribution of 680 liters.7 It is thought to distribute into most tissues including the liver.
- Protein binding
Elbasvir is more than 99.9% bound to plasma proteins.7 It binds both human serum albumin and α1-acid glycoprotein.
- Metabolism
Elbasvir is partially eliminated by oxidative metabolism meditated by CYP3A.7 No circulating metabolites of elbasvir have been detected in human plasma.
- Route of elimination
Elbasvir is mainly eliminated in the feces (90%) with very little eliminated in the urine (<1%).7
- Half-life
The geometric mean apparent terminal half-life for elbasvir is 24 hours in HCV-infected subjects.7
- Clearance
The clearance of elbasvir has not been determined.7
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most commonly reported adverse reactions of all intensity (greater than or equal to 5% in placebo-controlled trials) were fatigue, headache, and nausea.7
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Elbasvir can be increased when it is combined with Abametapir. Abatacept The metabolism of Elbasvir can be increased when combined with Abatacept. Abemaciclib Elbasvir may decrease the excretion rate of Abemaciclib which could result in a higher serum level. Abiraterone The metabolism of Elbasvir can be decreased when combined with Abiraterone. Acalabrutinib The metabolism of Elbasvir can be decreased when combined with Acalabrutinib. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Elbasvir. Adalimumab The metabolism of Elbasvir can be increased when combined with Adalimumab. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Elbasvir. Afatinib Elbasvir may decrease the excretion rate of Afatinib which could result in a higher serum level. Alfentanil The metabolism of Elbasvir can be decreased when combined with Alfentanil. 
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- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of elbasvir. Co-administration of Elbasvir with St. John's Wort is contraindicated.
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A, which may increase the serum levels of elbasvir, a CYP3A substrate.
- Take at the same time every day.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ZEPATIER Elbasvir (50 MG) + Grazoprevir (100 MG) Tablet, film coated Oral บริษัท เอ็มเอสดี (ประเทศไทย) จำกัด 2017-06-09 2020-08-13 Thailand 
Zepatier Elbasvir (50 mg) + Grazoprevir (100 mg) Tablet, film coated Oral Merck Sharp & Dohme B.V. 2016-09-08 Not applicable EU 
Zepatier Elbasvir (50 mg/1) + Grazoprevir (100 mg/1) Tablet, film coated Oral Merck Sharp & Dohme Corp. 2016-01-28 Not applicable US 
Zepatier Elbasvir (50 mg) + Grazoprevir (100 mg) Tablet Oral Merck Ltd. 2016-01-25 Not applicable Canada 
ZEPATIER 50 MG/100 MG FİLM KAPLI TABLET, 28 ADET Elbasvir (50 mg) + Grazoprevir (100 mg) Tablet, coated Oral MERCK SHARP DOHME İLAÇLARI LTD. ŞTİ. 2020-08-14 Not applicable Turkey 
ZEPATIER FILM-COATED TABLET 50MG/100MG Elbasvir (50.00 mg) + Grazoprevir (100.0 mg) Tablet, film coated Oral MSD PHARMA (SINGAPORE) PTE. LTD. 2018-01-11 Not applicable Singapore ZEPATIER® TABLETAS RECUBIERTAS Elbasvir (50 mg) + Grazoprevir (100 mg) Tablet, coated Oral BEND RESEARCH INC. 2018-07-25 Not applicable Colombia 
Categories
- ATC Codes
- J05AP54 — Elbasvir and grazoprevir
- J05AP — Antivirals for treatment of HCV infections
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals for treatment of HCV infections
- BCRP/ABCG2 Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Inhibitors
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Experimental Unapproved Treatments for COVID-19
- Hepatitis C Virus NS5A Inhibitor
- Heterocyclic Compounds, Fused-Ring
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Treatments for Hepatitis C
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as valine and derivatives. These are compounds containing valine or a derivative thereof resulting from reaction of valine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Valine and derivatives
- Alternative Parents
- Alpha amino acid amides / Indoles / N-acylpyrrolidines / Benzene and substituted derivatives / Tertiary carboxylic acid amides / Pyrroles / Heteroaromatic compounds / Imidazoles / Methylcarbamates / Organic carbonic acids and derivatives show 7 more
- Substituents
- Alpha-amino acid amide / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Carboxamide group / Heteroaromatic compound show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Hepatitis C Virus
- SARS-CoV-2
Chemical Identifiers
- UNII
- 632L571YDK
- CAS number
- 1370468-36-2
- InChI Key
- BVAZQCUMNICBAQ-PZHYSIFUSA-N
- InChI
- InChI=1S/C49H55N9O7/c1-27(2)41(54-48(61)63-5)45(59)56-20-10-14-37(56)43-50-25-34(52-43)30-17-19-36-32(22-30)23-39-33-18-16-31(24-40(33)65-47(58(36)39)29-12-8-7-9-13-29)35-26-51-44(53-35)38-15-11-21-57(38)46(60)42(28(3)4)55-49(62)64-6/h7-9,12-13,16-19,22-28,37-38,41-42,47H,10-11,14-15,20-21H2,1-6H3,(H,50,52)(H,51,53)(H,54,61)(H,55,62)/t37-,38-,41-,42-,47-/m0/s1
- IUPAC Name
- methyl N-[(2S)-1-[(2S)-2-{5-[(9S)-14-{2-[(2S)-1-[(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}-9-phenyl-8-oxa-10-azatetracyclo[8.7.0.0^{2,7}.0^{11,16}]heptadeca-1(17),2(7),3,5,11(16),12,14-heptaen-5-yl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate
- SMILES
- [H][C@]1(CCCN1C(=O)[C@@H](NC(=O)OC)C(C)C)C1=NC=C(N1)C1=CC2=C(C=C1)N1[C@@H](OC3=C(C=CC(=C3)C3=CN=C(N3)[C@]3([H])CCCN3C(=O)[C@@H](NC(=O)OC)C(C)C)C1=C2)C1=CC=CC=C1
References
- Synthesis Reference
Coburn CA, Meinke PT, Chang W, Fandozzi CM, Graham DJ, Hu B, Huang Q, Kargman S, Kozlowski J, Liu R, McCauley JA, Nomeir AA, Soll RM, Vacca JP, Wang D, Wu H, Zhong B, Olsen DB, Ludmerer SW: Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013 Dec;8(12):1930-40. doi: 10.1002/cmdc.201300343. Epub 2013 Oct 14.
- General References
- Bell AM, Wagner JL, Barber KE, Stover KR: Elbasvir/Grazoprevir: A Review of the Latest Agent in the Fight against Hepatitis C. Int J Hepatol. 2016;2016:3852126. doi: 10.1155/2016/3852126. Epub 2016 Jun 15. [Article]
- Coburn CA, Meinke PT, Chang W, Fandozzi CM, Graham DJ, Hu B, Huang Q, Kargman S, Kozlowski J, Liu R, McCauley JA, Nomeir AA, Soll RM, Vacca JP, Wang D, Wu H, Zhong B, Olsen DB, Ludmerer SW: Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013 Dec;8(12):1930-40. doi: 10.1002/cmdc.201300343. Epub 2013 Oct 14. [Article]
- Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [Article]
- Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [Article]
- Balasubramaniam M, Reis RS: Computational Target-Based Drug Repurposing of Elbasvir, an Antiviral Drug Predicted to Bind Multiple SARS-CoV-2 Proteins ChemRxiv. [Article]
- American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
- Zepatier FDA label [Link]
- External Links
- KEGG Drug
- D10625
- PubChem Compound
- 71661251
- PubChem Substance
- 347827988
- ChemSpider
- 30843797
- 1734628
- ChEBI
- 132967
- ChEMBL
- CHEMBL3039514
- ZINC
- ZINC000150588351
- PharmGKB
- PA166163436
- RxList
- RxList Drug Page
- Wikipedia
- Elbasvir
- FDA label
- Download (441 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Disorder of Transplanted Kidney / Hepatitis C Virus (HCV) Infection / Renal Insufficiency,Chronic 1 4 Completed Prevention Kidney Failure 1 4 Completed Treatment Chronic Hepatitis C Virus (HCV) Infection 2 4 Completed Treatment Chronic Kidney Disease, Stage 3 (Moderate) / Hepatitis C Virus (HCV) Infection 1 4 Completed Treatment End Stage Renal Disease (ESRD) / Hepatitis C Virus (HCV) Infection 1 4 Completed Treatment Hemodialysis Treatment / Hepatitis C Virus (HCV) Infection / Hospital Acquired Infections 1 4 Completed Treatment Hepatitis C Virus (HCV) Infection 1 4 Completed Treatment Hepatitis C Virus (HCV) Infection / Substance Abuse, Intravenous / Substance Use Disorders (SUD) 1 4 Recruiting Basic Science Cardiovascular Disease (CVD) / Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 4 Recruiting Treatment Chronic Hepatitis C Virus (HCV) Infection 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet, film coated Oral Tablet, coated Oral Tablet, film coated Oral 50.00 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8871759 No 2014-10-28 2031-05-04 US US7973040 No 2011-07-05 2029-07-24 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00457 mg/mL ALOGPS logP 5.6 ALOGPS logP 6.14 ChemAxon logS -5.3 ALOGPS pKa (Strongest Acidic) 11.11 ChemAxon pKa (Strongest Basic) 6.06 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 188.8 Å2 ChemAxon Rotatable Bond Count 13 ChemAxon Refractivity 241.52 m3·mol-1 ChemAxon Polarizability 100.15 Å3 ChemAxon Number of Rings 9 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- Kind
- Protein
- Organism
- Hepatitis C Virus
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Not Available
- Gene Name
- NS5A
- Uniprot ID
- Q5L478
- Uniprot Name
- Nonstructural protein 5A
- Molecular Weight
- 48598.34 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxygen binding
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57525.03 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Monooxygenase activity
- Specific Function
- Exhibits low testosterone 6-beta-hydroxylase activity.
- Gene Name
- CYP3A43
- Uniprot ID
- Q9HB55
- Uniprot Name
- Cytochrome P450 3A43
- Molecular Weight
- 57669.21 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created on April 07, 2016 16:37 / Updated on March 04, 2021 09:26