Identification
NameEntecavir
Accession NumberDB00442  (APRD00948)
TypeSmall Molecule
GroupsApproved, Investigational
Description

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.

Structure
Thumb
Synonyms
Anhydrous entecavir
Entecavir
Entecavir (anhydrous)
Entecavir anhydrous
Entecavirum
External IDs BMS-200475-01 / ETV / SQ34676
Product Ingredients
IngredientUNIICASInChI KeyDetails
Entecavir monohydrate5968Y6H45M 209216-23-9YXPVEXCTPGULBZ-WQYNNSOESA-NDetails
Entecavir triphosphateNot AvailableNot AvailableNot applicableDetails
Product Images
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Auro-entecavirTablet0.5 mgOralAuro Pharma Inc2015-12-01Not applicableCanada
BaracludeTablet0.5 mgOralBristol Myers Squibb2006-09-12Not applicableCanada
BaracludeTablet, film coated.5 mg/1OralE.R. Squibb & Sons, L.L.C.2005-03-29Not applicableUs
BaracludeTablet, film coated1 mgOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
BaracludeTablet, film coated1 mgOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
BaracludeTablet, film coated1 mgOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
BaracludeSolution0.05 mg/mlOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
BaracludeTablet, film coated1 mg/1OralE.R. Squibb & Sons, L.L.C.2005-03-29Not applicableUs
BaracludeTablet, film coated0.5 mgOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
BaracludeSolution.05 mg/mLOralE.R. Squibb & Sons, L.L.C.2005-03-29Not applicableUs
BaracludeTablet, film coated0.5 mgOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
BaracludeTablet, film coated0.5 mgOralBristol Myers Squibb Pharma Eeig2006-06-26Not applicableEu
EntecavirTablet, film coated.5 mg/1OralPar Pharmaceutical2014-08-18Not applicableUs
EntecavirTablet, film coated1 mg/1OralPar Pharmaceutical2014-08-18Not applicableUs
Gpc-entecavirTablet0.5 mgOralGeneric Partners (Canada) Inc.Not applicableNot applicableCanada
PMS-entecavirTablet1 mgOralPharmascience Inc2014-09-10Not applicableCanada
PMS-entecavirTablet0.5 mgOralPharmascience Inc2014-09-09Not applicableCanada
Sandoz EntecavirTablet0.5 mgOralSandoz Canada IncorporatedNot applicableNot applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-entecavirTablet0.5 mgOralApotex Corporation2013-01-18Not applicableCanada
EntecavirTablet.5 mg/1OralCamber Pharmaceuticals2015-08-21Not applicableUs
EntecavirTablet.5 mg/1OralLucid Pharma Llc2017-02-06Not applicableUs
EntecavirTablet, film coated1 mg/1OralCipla Limited2016-12-06Not applicableUs
EntecavirTablet, film coated.5 mg/1OralMarlex Pharmaceuticals Inc2016-03-01Not applicableUs
EntecavirTablet, film coated1 mg/1OralTeva2014-09-04Not applicableUs00093 5787 56 nlmimage10 ba43dd0e
EntecavirTablet, film coated1 mg/1OralAmneal Pharmaceuticals2014-11-28Not applicableUs
EntecavirTablet1 mg/1OralAurobindo Pharma2015-08-26Not applicableUs
EntecavirTablet, coated.5 mg/1OralPar Pharmaceutical2017-03-29Not applicableUs
EntecavirTablet, film coated.5 mg/1OralCipla Limited2016-12-06Not applicableUs
EntecavirTablet1 mg/1OralCamber Pharmaceuticals2015-08-21Not applicableUs
EntecavirTablet, film coated.5 mg/1OralAv Kare, Inc.2016-02-24Not applicableUs
EntecavirTablet1 mg/1OralLucid Pharma Llc2017-02-06Not applicableUs
EntecavirTablet, film coated1 mg/1OralMarlex Pharmaceuticals Inc2016-03-01Not applicableUs
EntecavirTablet, film coated.5 mg/1OralNorth Star Rx Llc2017-06-15Not applicableUs
EntecavirTablet.5 mg/1OralAmerincan Health Packaging2016-08-15Not applicableUs
EntecavirTablet, coated1 mg/1OralPar Pharmaceutical2017-03-29Not applicableUs
EntecavirTablet, film coated.5 mg/1OralTeva2014-09-04Not applicableUs
EntecavirTablet, film coated.5 mg/1OralAmneal Pharmaceuticals2014-11-28Not applicableUs
EntecavirTablet, film coated1 mg/1OralAv Kare, Inc.2016-02-24Not applicableUs
EntecavirTablet.5 mg/1OralAurobindo Pharma2015-08-26Not applicableUs
EntecavirTablet, film coated1 mg/1OralNorth Star Rx Llc2017-06-15Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BarcavirIncepta
CaavirelPMP
EntalivDr. Reddy's Laboratories
TeviralACI
Brand mixturesNot Available
Categories
UNIINNU2O4609D
CAS number142217-69-4
WeightAverage: 277.2792
Monoisotopic: 277.117489371
Chemical FormulaC12H15N5O3
InChI KeyQDGZDCVAUDNJFG-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)[[email protected]]1C[[email protected]](O)[C@@H](CO)C1=C
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.

Structured Indications
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.

TargetKindPharmacological actionActionsOrganismUniProt ID
DNANucleotideyes
other
Humannot applicabledetails
Related Articles
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 distributionNot 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 eliminationNot 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]
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.

Affected organisms
  • Hepatitis B virus
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
GanciclovirThe risk or severity of adverse effects can be increased when Ganciclovir is combined with Entecavir.Approved, Investigational
RibavirinRibavirin may increase the hepatotoxic activities of Entecavir.Approved
ValganciclovirThe risk or severity of adverse effects can be increased when Valganciclovir is combined with Entecavir.Approved, Investigational
Food Interactions
  • Take on an empty stomach.
  • Taking the product with a high-fat meal or a light snack reduces the maximal concentration by 44 to 46% and total exposure by 18 to 20%.
References
Synthesis ReferenceUS5206244
General ReferencesNot Available
External Links
ATC CodesJ05AF10 — Entecavir
AHFS Codes
  • 08:18.32
PDB EntriesNot Available
FDA labelDownload (628 KB)
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHepatitis B,Chronic1
1CompletedTreatmentViral Hepatitis B1
1RecruitingTreatmentChronic Hepatitis B Infection1
1RecruitingTreatmentChronic Hepatitis B Infection / Viral Hepatitis B1
1RecruitingTreatmentHepatitis B Virus (HBV)1
1, 2Active Not RecruitingTreatmentHepatitis B,Chronic1
1, 2CompletedTreatmentChronic Hepatitis B Infection1
1, 2Not Yet RecruitingTreatmentChronic Hepatitis B Infection2
1, 2Unknown StatusTreatmentChronic Hepatitis B Infection1
2Active Not RecruitingTreatmentHepatitis B,Chronic1
2CompletedTreatmentChronic Hepatitis B Infection6
2CompletedTreatmentHBV / Hepatitis B Virus (HBV)1
2CompletedTreatmentHepatic Failure1
2CompletedTreatmentHepatitis B Virus (HBV)1
2CompletedTreatmentHepatitis B,Chronic1
2RecruitingTreatmentHepatitis B,Chronic1
2RecruitingTreatmentNeoplasms, Colorectal1
2RecruitingTreatmentStomach Neoplasms1
2TerminatedTreatmentChronic Hepatitis B Infection1
2TerminatedTreatmentHepatitis D / Viral Hepatitis B1
2TerminatedTreatmentLiver Fibrosis Due to Chronic Hepatitis B Infection1
2Unknown StatusPreventionHepatitis B Reactivation / Non-Hodgkin's Lymphoma (NHL)1
2Unknown StatusTreatmentChronic Hepatitis B Infection1
2, 3CompletedTreatmentLiver Cancer1
2, 3CompletedTreatmentViral Hepatitis B1
2, 3RecruitingTreatmentChronic Hepatitis C Infection / HBV Coinfection / Hepatitis B Reactivation1
2, 3RecruitingTreatmentHepatocellular,Carcinoma1
3Active Not RecruitingTreatmentChronic Hepatitis B Virus, Pediatric1
3Active Not RecruitingTreatmentViral Hepatitis B1
3CompletedPreventionHepatitis B,Chronic1
3CompletedTreatmentAntiviral Treatment of Chronic Hepatitis B1
3CompletedTreatmentChronic Diseases / Viral Hepatitis B1
3CompletedTreatmentChronic Hepatitis B Infection4
3CompletedTreatmentChronic Hepatitis B Infection / Viral Hepatitis B1
3CompletedTreatmentChronic Hepatitis B Virus1
3CompletedTreatmentChronic Viral Hepatitis B Without Delta-agent1
3CompletedTreatmentHIV Disease1
3CompletedTreatmentHepatitis B,Chronic3
3CompletedTreatmentLiver Diseases / Transplantation, Liver / Viral Hepatitis B1
3CompletedTreatmentMalignancies / Viral Hepatitis B1
3CompletedTreatmentViral Hepatitis B2
3RecruitingTreatmentHepatitis B,Chronic2
3TerminatedPreventionAnkylosing Spondylitis (AS) / Chronic Hepatitis B Infection / Juvenile Idiopathic Arthritis (JIA) / Psoriatic Arthritis / Rheumatoid Arthritis1
3TerminatedTreatmentChronic Hepatitis B Infection1
3Unknown StatusTreatmentHepatitis B,Chronic1
4Active Not RecruitingTreatmentChronic Hepatitis B Infection1
4Active Not RecruitingTreatmentChronic Viral Hepatitis B Without Delta-agent2
4Active Not RecruitingTreatmentHepatitis B,Chronic2
4CompletedPreventionNon Hodgkin Lymphoma (NHL) / Viral Hepatitis B1
4CompletedTreatmentChronic Hepatitis B Infection4
4CompletedTreatmentHepatitis B Infection1
4CompletedTreatmentHepatitis B,Chronic8
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Viral Hepatitis B1
4CompletedTreatmentViral Hepatitis B1
4Enrolling by InvitationTreatmentChronic Hepatitis B Infection1
4Not Yet RecruitingTreatmentPortal Hypertension2
4RecruitingPreventionExposure to Hepatitis B Virus / Hepatitis B Reactivation / Rheumatoid Arthritis1
4RecruitingTreatmentChronic Hepatitis B Infection8
4RecruitingTreatmentFibrosis, Liver1
4RecruitingTreatmentHepatitis B Virus Associated Nephrotic Syndrome1
4RecruitingTreatmentHepatitis B,Chronic1
4RecruitingTreatmentLiver Cirrhosis2
4RecruitingTreatmentLiver Cirrhosis Due to Hepatitis B Virus1
4RecruitingTreatmentLiver Cirrhosis / Viral Hepatitis B1
4RecruitingTreatmentViral Hepatitis B2
4TerminatedNot AvailableFibrosis, Liver / Hepatitis B,Chronic1
4TerminatedDiagnosticAcidosis, Respiratory1
4TerminatedTreatmentChronic Hepatitis B Infection2
4Unknown StatusPreventionHepatitis / HepatitisB / Tuberculosis1
4Unknown StatusTreatmentChronic Hepatitis B Infection5
4Unknown StatusTreatmentChronic Hepatitis B Infection / Hepatic Steatosis1
4Unknown StatusTreatmentChronic Hepatitis B Infection / Inadequate Response / Nucleos(t)Ide Analogues Treatment1
4Unknown StatusTreatmentCirrhosis Due to Hepatitis B1
4Unknown StatusTreatmentCirrhosis, Decompensated / Hepatitis B Virus (HBV)1
4Unknown StatusTreatmentHepatitis B,Chronic4
4Unknown StatusTreatmentHepatitis, Chronic1
4Unknown StatusTreatmentHepatocellular,Carcinoma1
4Unknown StatusTreatmentViral Hepatitis B1
4WithdrawnTreatmentHepatitis B,Chronic2
Not AvailableActive Not RecruitingNot AvailableLiver Cirrhosis / Viral Hepatitis B1
Not AvailableActive Not RecruitingPreventionNon-Hodgkin's Lymphoma (NHL)1
Not AvailableActive Not RecruitingTreatmentChronic Heptitis B1
Not AvailableCompletedNot AvailableChronic Hepatitis B Infection1
Not AvailableCompletedNot AvailableEntecavir for Chronic Hepatitis B Patients1
Not AvailableCompletedNot AvailableHepatitis B,Chronic1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHepatitis B,Chronic1
Not AvailableCompletedTreatmentHepatocellular,Carcinoma / Viral Hepatitis B1
Not AvailableCompletedTreatmentPrimary Liver Cancers1
Not AvailableNo Longer AvailableNot AvailableChronic Diseases / Viral Hepatitis B1
Not AvailableNot Yet RecruitingNot AvailableChronic Hepatitis B Infection1
Not AvailableRecruitingTreatmentHepatitis B,Chronic1
Not AvailableTerminatedNot AvailableViral Hepatitis B1
Not AvailableUnknown StatusNot AvailableChronic Hepatitis B Infection / Hepatocellular,Carcinoma1
Not AvailableUnknown StatusNot AvailableViral Hepatitis B1
Not AvailableUnknown StatusTreatmentChronic Hepatitis B Infection1
Not AvailableUnknown StatusTreatmentViral Hepatitis B1
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
Packagers
Dosage forms
FormRouteStrength
SolutionOral.05 mg/mL
SolutionOral0.05 mg/ml
TabletOral0.5 mg
Tablet, film coatedOral0.5 mg
Tablet, film coatedOral1 mg
TabletOral.5 mg/1
TabletOral1 mg/1
Tablet, coatedOral.5 mg/1
Tablet, coatedOral1 mg/1
Tablet, film coatedOral.5 mg/1
Tablet, film coatedOral1 mg/1
TabletOral1 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)
CA2053339 No2001-05-292011-10-11Canada
US5206244 Yes1995-08-212015-08-21Us
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
ClassNucleoside and nucleotide analogues
Sub ClassNot Available
Direct ParentNucleoside and nucleotide analogues
Alternative ParentsHypoxanthines / 6-oxopurines / Pyrimidones / Aminopyrimidines and derivatives / N-substituted imidazoles / Cyclopentanols / Vinylogous amides / Heteroaromatic compounds / Cyclic alcohols and derivatives / Azacyclic compounds
Substituents6-oxopurine / Hypoxanthine / Purinone / Purine / Imidazopyrimidine / Aminopyrimidine / Pyrimidone / Cyclopentanol / Pyrimidine / N-substituted imidazole
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorssecondary alcohol, oxopurine, primary alcohol, 2-aminopurines (CHEBI:473990 )

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
other
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
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. [PubMed:17125436 ]
  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. [PubMed:20169198 ]
Drug created on June 13, 2005 07:24 / Updated on July 22, 2017 18:05