- Accession Number
- DB00442 (APRD00948)
- Small Molecule
- Approved, Investigational
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.
- Anhydrous entecavir
- Entecavir (anhydrous)
- Entecavir anhydrous
- External IDs
- BMS-200475-01 / ETV / SQ34676
- Product Ingredients
Ingredient UNII CAS InChI Key Entecavir monohydrate 5968Y6H45M 209216-23-9 YXPVEXCTPGULBZ-WQYNNSOESA-N Entecavir triphosphate Not Available Not Available Not applicable
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Baraclude Tablet 0.5 mg Oral Bristol Myers Squibb 2006-09-12 Not applicable Baraclude Tablet, film coated 0.5 mg Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable Baraclude Tablet, film coated 1 mg Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable Baraclude Tablet, film coated 1.0 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2005-03-29 Not applicable Baraclude Solution 0.05 mg/ml Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable Baraclude Tablet, film coated 0.5 mg Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable Baraclude Tablet, film coated 0.5 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2005-03-29 Not applicable Baraclude Tablet, film coated 1 mg Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable Baraclude Tablet, film coated 1 mg Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable Baraclude Tablet, film coated 0.5 mg Oral Bristol Myers Squibb Pharma Eeig 2006-06-26 Not applicable
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Apo-entecavir Tablet 0.5 mg Oral Apotex Corporation 2013-01-18 Not applicable Auro-entecavir Tablet 0.5 mg Oral Auro Pharma Inc 2015-12-01 Not applicable Entecavir Tablet, film coated 0.5 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2014-09-04 Not applicable Entecavir Tablet, film coated 1 mg/1 Oral Cadila Healthcare Limited 2017-08-10 Not applicable Entecavir Tablet, film coated 0.5 mg/1 Oral Cipla USA Inc. 2016-12-06 Not applicable Entecavir Tablet, film coated 1 mg/1 Oral Marlex Pharmaceuticals Inc 2016-03-01 Not applicable Entecavir Tablet, film coated 0.5 mg/1 Oral Av Kare, Inc. 2016-02-24 Not applicable Entecavir Tablet, coated 1 mg/1 Oral Par Pharmaceutical 2017-03-29 Not applicable Entecavir Tablet, film coated 1 mg/1 Oral Northstar RxLLC 2017-06-15 Not applicable Entecavir Tablet 0.5 mg/1 Oral Aurobindo Pharma Limited 2015-08-26 Not applicable
- International/Other Brands
- Barcavir (Incepta) / Caavirel (PMP) / Entaliv (Dr. Reddy's Laboratories) / Teviral (ACI)
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Cytochrome P-450 CYP1A2 Substrates
- Direct Acting Antivirals
- Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor
- Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
- Nucleoside Reverse Transcriptase Inhibitors
- Nucleosides and Nucleotides
- CAS number
- Average: 277.2792
- Chemical Formula
- InChI Key
- IUPAC Name
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.
- Associated Conditions
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.
Target Actions Organism ADNAother Humans
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%.
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.
- 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]
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
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
Drug Interaction (R)-warfarin The metabolism of (R)-warfarin can be decreased when combined with Entecavir. 3-isobutyl-1-methyl-7H-xanthine The serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Entecavir. 6-O-benzylguanine The serum concentration of 6-O-benzylguanine can be increased when it is combined with Entecavir. 7-Deazaguanine The serum concentration of 7-Deazaguanine can be increased when it is combined with Entecavir. 7,9-Dimethylguanine The serum concentration of 7,9-Dimethylguanine can be increased when it is combined with Entecavir. 8-azaguanine The serum concentration of 8-azaguanine can be increased when it is combined with Entecavir. 8-chlorotheophylline The serum concentration of 8-chlorotheophylline can be increased when it is combined with Entecavir. 9-Deazaguanine The serum concentration of 9-Deazaguanine can be increased when it is combined with Entecavir. 9-Methylguanine The serum concentration of 9-Methylguanine can be increased when it is combined with Entecavir. Abatacept The metabolism of Entecavir can be increased when combined with Abatacept.
- 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%.
- Synthesis Reference
- General References
- Not Available
- External Links
- ATC Codes
- J05AF10 — Entecavir
- AHFS Codes
- 08:18.32 — Nucleosides and Nucleotides
- FDA label
- Download (628 KB)
- Clinical Trials
- Bristol myers squibb
- Bristol-Myers Squibb Co.
- E.R. Squibb and Sons LLC
- Dosage forms
Form Route Strength Solution Oral 0.05 mg/ml Solution Oral 0.05 mg/1mL Tablet Oral 0.5 mg Tablet, film coated Oral 0.5 mg Tablet, film coated Oral 1 mg Tablet Oral 0.5 mg/1 Tablet Oral 1 mg/1 Tablet, coated Oral 0.5 mg/1 Tablet, coated Oral 1 mg/1 Tablet, film coated Oral 0.5 mg/1 Tablet, film coated Oral 1 mg/1 Tablet, film coated Oral 1.0 mg/1 Tablet Oral 1 mg
Unit description Cost Unit Baraclude 0.5 mg tablet 28.94USD tablet Baraclude 1 mg tablet 28.94USD tabletDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patent Number Pediatric Extension Approved Expires (estimated) CA2053339 No 2001-05-29 2011-10-11 US5206244 Yes 1993-04-27 2015-08-21
- Experimental Properties
Property Value Source water solubility Slightly soluble (2.4 mg/mL at pH 7.9, 25 °C) Not Available logP -0.8 Not Available
- Predicted Properties
Property Value Source Water Solubility 6.59 mg/mL ALOGPS logP -0.81 ALOGPS logP -1.4 ChemAxon logS -1.6 ALOGPS pKa (Strongest Acidic) 8 ChemAxon pKa (Strongest Basic) 2.77 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 7 ChemAxon Hydrogen Donor Count 4 ChemAxon Polar Surface Area 125.76 Å2 ChemAxon Rotatable Bond Count 2 ChemAxon Refractivity 71 m3·mol-1 ChemAxon Polarizability 27.31 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon
- Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.873 Caco-2 permeable - 0.7601 P-glycoprotein substrate Substrate 0.5802 P-glycoprotein inhibitor I Non-inhibitor 0.863 P-glycoprotein inhibitor II Non-inhibitor 0.9185 Renal organic cation transporter Non-inhibitor 0.8465 CYP450 2C9 substrate Non-substrate 0.8817 CYP450 2D6 substrate Non-substrate 0.8164 CYP450 3A4 substrate Non-substrate 0.5346 CYP450 1A2 substrate Non-inhibitor 0.7641 CYP450 2C9 inhibitor Non-inhibitor 0.848 CYP450 2D6 inhibitor Non-inhibitor 0.915 CYP450 2C19 inhibitor Non-inhibitor 0.87 CYP450 3A4 inhibitor Non-inhibitor 0.9647 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9552 Ames test Non AMES toxic 0.7523 Carcinogenicity Non-carcinogens 0.8026 Biodegradation Not ready biodegradable 0.9669 Rat acute toxicity 2.3879 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8865 hERG inhibition (predictor II) Non-inhibitor 0.9062
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available 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
- 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.
- Organic compounds
- Super Class
- Nucleosides, nucleotides, and analogues
- 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 compoundsPrimary amines / Primary alcohols / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives show 5 more
- 6-oxopurine / Hypoxanthine / Purinone / Purine / Imidazopyrimidine / Aminopyrimidine / Pyrimidone / Cyclopentanol / Pyrimidine / N-substituted imidazoleAzole / Cyclic alcohol / Heteroaromatic compound / Imidazole / Vinylogous amide / Secondary alcohol / Azacycle / Organoheterocyclic compound / Primary alcohol / Primary amine / Alcohol / Organic nitrogen compound / Hydrocarbon derivative / Organic oxide / Organopnictogen compound / Organic oxygen compound / Amine / Organonitrogen compound / Organooxygen compound / Aromatic heteropolycyclic compound show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- secondary alcohol, oxopurine, primary alcohol, 2-aminopurines (CHEBI:473990)
- 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
- 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]
- 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 February 16, 2019 05:56