Entecavir

Identification

Summary

Entecavir is a nucleoside analogue used in the treatment of chronic hepatitis B for patients with active viral replication, histological evidence of active disease, or persistent elevations in liver transaminases.

Brand Names
Baraclude
Generic Name
Entecavir
DrugBank Accession Number
DB00442
Background

Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude (BMS).

Entecavir is a guanine analogue that inhibits all three steps in the viral replication process, and the manufacturer claims that it is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir). It was approved by the U.S. Food and Drug Administration (FDA) in March 2005.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 277.2792
Monoisotopic: 277.117489371
Chemical Formula
C12H15N5O3
Synonyms
  • Anhydrous entecavir
  • Entecavir
  • Entecavir (anhydrous)
  • Entecavir anhydrous
  • Entecavirum
External IDs
  • BMS-200475-01
  • ETV
  • SQ34676

Pharmacology

Indication

For the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine.

Mechanism of action

By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity.

TargetActionsOrganism
ADNA
other
Humans
Absorption

Absorption Following oral administration in healthy subjects, entecavir peak plasma concentrations occurred between 0.5 and 1.5 hours. In healthy subjects, the bioavailability of the tablet is 100% relative to the oral solution.

Volume of distribution

Not Available

Protein binding

Binding of entecavir to human serum proteins in vitro is approximately 13%.

Metabolism

Entecavir is not a substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system. Entecavir is efficiently phosphorylated to the active triphosphate form.

Route of elimination

Not Available

Half-life

After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128-149 hours. The phosphorylated metabolite has a half-life of 15 hours.

Clearance
  • renal cl=383.2 +/- 101.8 mL/min [Unimpaired renal function]
  • renal cl=197.9 +/- 78.1 mL/min [Mild impaired renal function]
  • renal cl=135.6 +/- 31.6 mL/min [Moderate impaired renal function]
  • renal cl=40.3 +/- 10.1 mL/min [severe impaired renal function]
  • apparent oral cl=588.1 +/- 153.7 mL/min [Unimpaired renal function]
  • apparent oral cl=309.2 +/- 62.6 mL/min [Mild impaired renal function]
  • apparent oral cl=226.3 +/- 60.1 mL/min [Moderate impaired renal function]
  • apparent oral cl=100.6 +/- 29.1 mL/min [severe impaired renal function]
  • apparent oral cl=50.6 +/- 16.5 mL/min [severe impaired renal function amnaged with Hemodialysis]
  • apparent oral cl=35.7 +/- 19.6 mL/min [severe impaired renal function amnaged with CAPD]
Adverse Effects
Medicalerrors
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Toxicity

Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

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.
DrugInteraction
AbametapirThe serum concentration of Entecavir can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Entecavir can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Entecavir can be increased when it is combined with Abiraterone.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Entecavir.
AcetaminophenThe metabolism of Entecavir can be decreased when combined with Acetaminophen.
AcyclovirThe metabolism of Acyclovir can be decreased when combined with Entecavir.
AdalimumabThe metabolism of Entecavir can be increased when combined with Adalimumab.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Entecavir.
AgomelatineThe metabolism of Agomelatine can be decreased when combined with Entecavir.
AlbendazoleThe metabolism of Albendazole can be increased when combined with Entecavir.
Interactions
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Food Interactions
  • Take on an empty stomach. Take 2 hours before or 2 hours after a meal.

Products

Products
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Product Ingredients
IngredientUNIICASInChI Key
Entecavir monohydrate5968Y6H45M209216-23-9YXPVEXCTPGULBZ-WQYNNSOESA-N
Entecavir triphosphateNot AvailableNot AvailableZTWBIZVVFNIRSF-HAFWLYHUSA-N
Product Images
International/Other Brands
Barcavir (Incepta) / Caavirel (PMP) / Entaliv (Dr. Reddy's Laboratories) / Teviral (ACI)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BaracludeTablet, film coated0.5 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
BaracludeTablet, film coated1.0 mg/1OralE.R. Squibb & Sons, L.L.C.2005-03-29Not applicableUS flag
BaracludeTablet, film coated0.5 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
BaracludeTablet, film coated0.5 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
BaracludeTablet, film coated0.5 mg/1OralE.R. Squibb & Sons, L.L.C.2005-03-29Not applicableUS flag
BaracludeSolution0.05 mg/mlOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
BaracludeTablet, film coated1 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
BaracludeTablet0.5 mgOralBristol Myers Squibb2006-09-12Not applicableCanada flag
BaracludeSolution0.05 mg/1mLOralE.R. Squibb & Sons, L.L.C.2005-03-29Not applicableUS flag
BaracludeTablet, film coated1 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel-entecavirTablet0.5 mgOralAccel Pharma Inc2020-03-11Not applicableCanada flag
Apo-entecavirTablet0.5 mgOralApotex Corporation2013-01-18Not applicableCanada flag
Auro-entecavirTablet0.5 mgOralAuro Pharma Inc2015-12-01Not applicableCanada flag
EntecavirTablet, film coated0.5 mg/1OralSolco Healthcare Llc2018-04-01Not applicableUS flag
EntecavirTablet, film coated0.5 mg/1OralYaopharma Co., Ltd.2020-10-31Not applicableUS flag
EntecavirTablet, film coated0.5 mg/1OralAmneal Pharmaceuticals LLC2014-11-28Not applicableUS flag
EntecavirTablet, film coated1 mg/1OralMarlex Pharmaceuticals Inc2016-03-01Not applicableUS flag
EntecavirTablet, coated1 mg/1OralPar Pharmaceutical, Inc.2017-03-292019-02-28US flag
EntecavirTablet1 mg/1OralAurobindo Pharma Limited2015-08-26Not applicableUS flag
EntecavirTablet1 mg/1OralAcetris Health, Llc2017-02-062020-01-01US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
BARACLUDE 0,5 MG FILM TABLET, 30 ADETEntecavir monohydrate (0.5 mg)Tablet, film coatedOralBRISTOL-MYERS SQUIBB İLAÇLARI INC. İSTANBUL ŞUBESİ2020-08-14Not applicableTurkey flag
BARACLUDE 1 MG FILM TABLET, 30 ADETEntecavir monohydrate (1 mg)Tablet, film coatedOralBRISTOL-MYERS SQUIBB İLAÇLARI INC. İSTANBUL ŞUBESİ2020-08-14Not applicableTurkey flag
HEDNAVIR 0,5 MG FILM TABLET, 30 ADETEntecavir monohydrate (0.5 mg)Tablet, film coatedOralATABAY KİMYA SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
HEDNAVIR 1 MG FILM TABLET, 30 ADETEntecavir monohydrate (1 mg)Tablet, film coatedOralATABAY KİMYA SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag

Categories

ATC Codes
J05AF10 — Entecavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as nucleoside and nucleotide analogues. These are analogues of nucleosides and nucleotides. These include phosphonated nucleosides, C-glycosylated nucleoside bases, analogues where the sugar unit is a pyranose, and carbocyclic nucleosides, among others.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Nucleoside and nucleotide analogues
Sub Class
Not Available
Direct Parent
Nucleoside and nucleotide analogues
Alternative Parents
Hypoxanthines / 6-oxopurines / Pyrimidones / Aminopyrimidines and derivatives / N-substituted imidazoles / Cyclopentanols / Vinylogous amides / Heteroaromatic compounds / Cyclic alcohols and derivatives / Azacyclic compounds
show 5 more
Substituents
6-oxopurine / Alcohol / Amine / Aminopyrimidine / Aromatic heteropolycyclic compound / Azacycle / Azole / Cyclic alcohol / Cyclopentanol / Heteroaromatic compound
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
secondary alcohol, oxopurine, primary alcohol, 2-aminopurines (CHEBI:473990)
Affected organisms
  • Hepatitis B virus

Chemical Identifiers

UNII
NNU2O4609D
CAS number
142217-69-4
InChI Key
QDGZDCVAUDNJFG-FXQIFTODSA-N
InChI
InChI=1S/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8-/m0/s1
IUPAC Name
2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one
SMILES
NC1=NC(=O)C2=C(N1)N(C=N2)[C@H]1C[C@H](O)[C@@H](CO)C1=C

References

Synthesis Reference
US5206244
General References
Not Available
Human Metabolome Database
HMDB0014585
KEGG Drug
D04008
PubChem Compound
153941
PubChem Substance
46504864
ChemSpider
135679
RxNav
1546027
ChEBI
473990
ChEMBL
CHEMBL713
ZINC
ZINC000003802690
Therapeutic Targets Database
DAP000697
PharmGKB
PA164784025
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Entecavir
AHFS Codes
  • 08:18.32 — Nucleosides and Nucleotides
FDA label
Download (628 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionExposure to Hepatitis B Virus / Reactivation of hepatitis B virus infection / Rheumatoid Arthritis1
4Active Not RecruitingTreatmentCirrhosis of the Liver / Viral Hepatitis B1
4Active Not RecruitingTreatmentHBV Coinfection / HCC1
4Active Not RecruitingTreatmentHepatitis B Chronic Infection1
4Active Not RecruitingTreatmentViral Hepatitis B1
4CompletedPreventionNon-Hodgkin's Lymphoma (NHL) / Viral Hepatitis B1
4CompletedTreatmentChronic Viral Hepatitis B Without Delta-agent2
4CompletedTreatmentCirrhosis of the Liver2
4CompletedTreatmentFibrosis, Liver1
4CompletedTreatmentHBeAg-Positive Chronic Hepatitis B1

Pharmacoeconomics

Manufacturers
  • Bristol myers squibb
Packagers
  • Bristol-Myers Squibb Co.
  • E.R. Squibb and Sons LLC
Dosage Forms
FormRouteStrength
SolutionOral
SolutionOral0.05 mg/ml
SolutionOral0.05 mg/1mL
Tablet, film coatedOral1.0 MG
SolutionOral5 mg
Tablet, coatedOral1 mg
TabletOral
TabletOral0.5 mg/1
TabletOral1 mg/1
Tablet, coatedOral0.5 mg/1
Tablet, coatedOral1 mg/1
Tablet, film coatedOral0.5 mg/1
Tablet, film coatedOral1 mg/1
Tablet, film coatedOral1.0 mg/1
Tablet, film coatedOral
Tablet, coatedOral0.5 mg
TabletOral0.5 mg
TabletOral1 mg
Tablet, film coatedOral0.5 mg
Tablet, film coatedOral1 mg
Prices
Unit descriptionCostUnit
Baraclude 0.5 mg tablet28.94USD tablet
Baraclude 1 mg tablet28.94USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2053339No2001-05-292011-10-11Canada flag
US5206244Yes1993-04-272015-08-21US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySlightly soluble (2.4 mg/mL at pH 7.9, 25 °C)Not Available
logP-0.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility6.59 mg/mLALOGPS
logP-0.81ALOGPS
logP-1.4ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)8ChemAxon
pKa (Strongest Basic)2.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area125.76 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity71 m3·mol-1ChemAxon
Polarizability27.31 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.873
Caco-2 permeable-0.7601
P-glycoprotein substrateSubstrate0.5802
P-glycoprotein inhibitor INon-inhibitor0.863
P-glycoprotein inhibitor IINon-inhibitor0.9185
Renal organic cation transporterNon-inhibitor0.8465
CYP450 2C9 substrateNon-substrate0.8817
CYP450 2D6 substrateNon-substrate0.8164
CYP450 3A4 substrateNon-substrate0.5346
CYP450 1A2 substrateNon-inhibitor0.7641
CYP450 2C9 inhibitorNon-inhibitor0.848
CYP450 2D6 inhibitorNon-inhibitor0.915
CYP450 2C19 inhibitorNon-inhibitor0.87
CYP450 3A4 inhibitorNon-inhibitor0.9647
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9552
Ames testNon AMES toxic0.7523
CarcinogenicityNon-carcinogens0.8026
BiodegradationNot ready biodegradable0.9669
Rat acute toxicity2.3879 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8865
hERG inhibition (predictor II)Non-inhibitor0.9062
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Other
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Sims KA, Woodland AM: Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection. Pharmacotherapy. 2006 Dec;26(12):1745-57. [Article]
  2. Walsh AW, Langley DR, Colonno RJ, Tenney DJ: Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir. PLoS One. 2010 Feb 12;5(2):e9195. doi: 10.1371/journal.pone.0009195. [Article]

Drug created on June 13, 2005 13:24 / Updated on June 18, 2021 14:15