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{{Short description|Chemical compound}}
{{Drugbox
{{Distinguish|Emtricitabine}}
{{Use dmy dates|date=July 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Verifiedfields = changed
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 464189683
| verifiedrevid = 464189683
⚫
| IUPAC_name = 2-Amino-9-[(1''S'',3''R'',4''S'')-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1''H''-purin-6-one
| image = Entecavir structure.svg
| image = Entecavir structure.svg
| width = 240
| width = 240
| alt =
| image2 = Entecavir ball-and-stick model.png
| image2 = Entecavir ball-and-stick model.png
| alt2 =
| caption =


<!--Clinical data-->
<!-- Clinical data -->
| pronounce = {{IPAc-en|ɛ|n|ˈ|t|ɛ|k|ə|v|ɪər}} {{respell|en|TEK|ə|veer}}
| pronounce = {{IPAc-en|ɛ|n|ˈ|t|ɛ|k|ə|v|ɪər}} {{respell|en|TEK|ə|veer}}
| tradename = Baraclude,<ref name=AHFS2016/> Entimate, others
| tradename = Baraclude, others
| Drugs.com = {{drugs.com|monograph|entecavir}}
| Drugs.com = {{drugs.com|monograph|entecavir}}
| MedlinePlus = a605028
| MedlinePlus = a605028
| licence_EU = yes
| DailyMedID = Entecavir
| licence_US = Entecavir
| pregnancy_AU = B3
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Entecavir (Baraclude) Use During Pregnancy | website=Drugs.com | date=3 December 2019 | url=https://www.drugs.com/pregnancy/entecavir.html | access-date=24 January 2021 | archive-date=7 November 2016 | archive-url=https://web.archive.org/web/20161107162421/https://www.drugs.com/pregnancy/entecavir.html | url-status=live }}</ref>
| pregnancy_US = C
| pregnancy_category=
⚫
| routes_of_administration = [[Oral administration|By mouth]]
| class =
| ATC_prefix = J05
⚫
| ATC_suffix = AF10
⚫
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU = S4
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only
| legal_US = Rx-only
| legal_US_comment = <ref name="Baraclude FDA label" />
⚫
| routes_of_administration = [[Oral administration|By mouth]]
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web | website=European Medicines Agency | title=Baraclude EPAR | date=26 June 2006 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/baraclude | access-date=5 July 2024 | archive-date=6 March 2024 | archive-url=https://web.archive.org/web/20240306150057/https://www.ema.europa.eu/en/medicines/human/EPAR/baraclude | url-status=live }}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only


<!--Pharmacokinetic data-->
<!-- Pharmacokinetic data -->
| bioavailability = n/a (≥70)<ref name="bmsPI"/>
| bioavailability = n/a (≥70)<ref name="Baraclude FDA label"/>
| protein_bound = 13% ''([[in vitro]])''
| protein_bound = 13% ''([[in vitro]])''
| metabolism = negligible/nil
| metabolism = negligible/nil
| metabolites =
| onset =
| elimination_half-life = 128–149 hours
| elimination_half-life = 128–149 hours
| duration_of_action =
| excretion = [[Kidney|Renal]] 62–73%
| excretion = [[Kidney]] 62–73%


<!--Identifiers-->
<!-- Identifiers -->
| CAS_number_Ref = {{cascite|changed|CAS}}
| CAS_number_Ref = {{cascite|changed|CAS}}
| CAS_number = 142217-69-4
| CAS_number = 142217-69-4
| ATC_prefix = J05
| CAS_supplemental =
⚫
| ATC_suffix = AF10
⚫
| ATC_supplemental =
| PubChem = 135398508
| PubChem = 135398508
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00442
| DrugBank = DB00442
⚫
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 135679
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 5968Y6H45M
| UNII = NNU2O4609D
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D04008
| KEGG = D04008
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 59902
| ChEBI = 473990
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 713
| ChEMBL = 713
| NIAID_ChemDB =
⚫
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 135679
| PDB_ligand =
| synonyms = ETV, BMS-200475-01

⚫
<!-- Chemical and physical data -->
⚫
| IUPAC_name = 2-Amino-9-[(1''S'',3''R'',4''S'')-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1''H''-purin-6-one
⚫
| C=12 | H=15 | N=5 | O=3
| SMILES = C=C1C(CC(C1CO)O)N2C=NC3=C2N=C(NC3=O)N
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChI = 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
| StdInChI_comment =
⚫
| C=12 | H=15 | N=5 | O=3
| smiles = O=C2/N=C(\Nc1n(cnc12)[C@@H]3C(=C)/[C@H](CO)[C@@H](O)C3)N
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = {{unbulleted list|YXPVEXCTPGULBZ-WQYNNSOESA-N|QDGZDCVAUDNJFG-FXQIFTODSA-N
| StdInChIKey = QDGZDCVAUDNJFG-FXQIFTODSA-N
| density =

| density_notes =
⚫
<!--Chemical data-->}}
|melting_point = 220
| melting_point = 220
| melting_high =
|melting_notes = value applies to entecavir monohydrate and is a minimum value<ref>{{cite encyclopedia |encyclopedia=The Merck Index |edition=14th |year=2006 |page=613 |isbn=978-0-911910-00-1 |title=The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals |last1=O'Neil }}</ref>
| melting_notes = value applies to entecavir monohydrate and is a minimum value<ref>{{cite encyclopedia |encyclopedia=The Merck Index |edition=14th |year=2006 |page=613 |isbn=978-0-911910-00-1 |title=The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals | vauthors = O'Neil MJ }}</ref>
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
}}

<!-- Definition and medical uses -->
<!-- Definition and medical uses -->
'''Entecavir''' ('''ETV'''), sold under the brand name '''Baraclude''', is an [[antiviral medication]] used in the treatment of [[hepatitis B virus]] (HBV) infection.<ref name=AHFS2016/> In those with both [[HIV/AIDS]] and HBV [[antiretroviral medication]] should also be used.<ref name=AHFS2016/> Entecavir is taken by mouth as a tablet or solution.<ref name=AHFS2016/>
'''Entecavir''', sold under the brand name '''Baraclude''', is an [[antiviral medication]] used in the treatment of [[hepatitis B virus]] infection.<ref name=AHFS2016/> In those with both [[HIV/AIDS]] and hepatitis B virus [[antiretroviral medication]] should also be used.<ref name=AHFS2016/> Entecavir is taken by mouth as a tablet or solution.<ref name=AHFS2016/>


<!-- Side effects and mechanism -->
<!-- Side effects and mechanism -->
Common side effects include headache, nausea, [[hyperglycemia|high blood sugar]], and decreased kidney function.<ref name=AHFS2016/> Severe side effects include [[hepatomegaly|enlargement of the liver]], [[lactic acidosis|high blood lactate levels]], and [[hepatitis|liver inflammation]] if the medication is stopped.<ref name=AHFS2016/> While there appears to be no harm from use during pregnancy, this use has not been well studied.<ref>{{cite web|title=Entecavir (Baraclude) Use During Pregnancy|url=https://www.drugs.com/pregnancy/entecavir.html|website=www.drugs.com|accessdate=6 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161107162421/https://www.drugs.com/pregnancy/entecavir.html|archive-date=7 November 2016}}</ref> Entecavir is in the [[nucleoside reverse transcriptase inhibitors]] (NRTIs) family of medications.<ref name=AHFS2016/><ref>{{cite book|last1=Shetty|first1=Kirti|last2=Wu|first2=George Y.|title=Chronic Viral Hepatitis: Diagnosis and Therapeutics|date=2009|publisher=Springer Science & Business Media|isbn=9781597455657|page=34|url=https://books.google.com/books?id=o67J8smzgHEC&pg=PA34|language=en}}</ref> It prevents the hepatitis B virus from multiplying by blocking [[reverse transcriptase]].<ref name=AHFS2016/>
Common side effects include headache, nausea, [[hyperglycemia|high blood sugar]], and decreased kidney function.<ref name=AHFS2016/> Severe side effects include [[hepatomegaly|enlargement of the liver]], [[lactic acidosis|high blood lactate levels]], and [[hepatitis|liver inflammation]] if the medication is stopped.<ref name=AHFS2016/> While there appears to be no harm from use during pregnancy, this use has not been well studied.<ref name="Drugs.com pregnancy" /> Entecavir is in the [[nucleoside reverse transcriptase inhibitors]] (NRTIs) family of medications.<ref name=AHFS2016/><ref>{{cite book| vauthors = Shetty K, Wu GY |title=Chronic Viral Hepatitis: Diagnosis and Therapeutics|date=2009|publisher=Springer Science & Business Media|isbn=9781597455657|page=34|url=https://books.google.com/books?id=o67J8smzgHEC&pg=PA34|language=en}}</ref> It prevents the hepatitis B virus from multiplying by blocking [[reverse transcriptase]].<ref name=AHFS2016/>


<!-- History and culture -->
<!-- History and culture -->
Entecavir was approved for medical use in 2005.<ref name=AHFS2016>{{cite web|title=Entecavir|url=https://www.drugs.com/monograph/entecavir.html|publisher=The American Society of Health-System Pharmacists|accessdate=28 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161220224057/https://www.drugs.com/monograph/entecavir.html|archive-date=20 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> In the United States, {{as of|2015}}, it is not available as a [[generic medication]].<ref name=Ric2015>{{cite book|last1=Hamilton|first1=Richart|title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=76}}</ref>
Entecavir was approved for medical use in 2005.<ref name=AHFS2016>{{cite web|title=Entecavir|url=https://www.drugs.com/monograph/entecavir.html|publisher=The American Society of Health-System Pharmacists|access-date=28 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161220224057/https://www.drugs.com/monograph/entecavir.html|archive-date=20 December 2016}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> It is available as a [[generic medication]].


==Medical uses==
==Medical uses==
Entecavir is mainly used to treat chronic hepatitis B infection in adults and children 2 years and older with active viral replication and evidence of active disease with elevations in liver enzymes.<ref name="bmsPI">"[http://packageinserts.bms.com/pi/pi_baraclude.pdf Baraclude (entecavir) Tablets for Oral Use & Oral Solution. U.S. Full Prescribing Information.] {{webarchive|url=https://web.archive.org/web/20140222055433/http://packageinserts.bms.com/pi/pi_baraclude.pdf |date=2014-02-22 }}" Bristol-Myers Squibb Company, 2005. Revised December 2013.</ref> It is also used to prevent HBV reinfection after liver transplant<ref>{{cite journal | last1 = Fung | first1 = J | last2 = Cheung | first2 = C | last3 = Chan | first3 = SC | display-authors = etal | year = 2011 | title = Entecavir Monotherapy is Effective in Suppressing Hepatitis B Virus After Liver Transplantation | journal = Gastroenterology | volume = 141 | issue = 4| pages = 1212–9 | doi=10.1053/j.gastro.2011.06.083 | pmid=21762659}}</ref> and to treat HIV patients infected with HBV. Entecavir is weakly active against HIV, but is not recommended for use in HIV-HBV co-infected patients without a fully suppressive anti-HIV regimen<ref>{{cite web|title=Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents|url=http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf|publisher=Panel on Antiretroviral Guidelines for Adults and Adolescents|accessdate=15 March 2015|url-status=live|archive-url=https://web.archive.org/web/20161101202407/https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf|archive-date=1 November 2016}}</ref> as it may select for resistance to lamivudine and emtricitabine in HIV.<ref>{{cite journal|last1=McMahon|first1=Moira|title=The Anti-Hepatitis B Drug Entecavir Inhibits HIV-1 Replication and Can Select HIV-1 Variants Resistant to Antiretroviral Drugs|journal=N Engl J Med|date=21 June 2007|issue=25|pages=2614–2621|pmid=17582071|doi=10.1056/NEJMoa067710|volume=356|pmc=3069686}}</ref>
Entecavir is mainly used to treat chronic hepatitis B infection in adults and children two years and older with active viral replication and evidence of active disease with elevations in liver enzymes.<ref name="Baraclude FDA label">{{cite web | title=Baraclude- entecavir tablet, film coated Baraclude- entecavir solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20 | access-date=24 January 2021 | archive-date=8 November 2016 | archive-url=https://web.archive.org/web/20161108140245/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20 | url-status=live }}</ref> It is also used to prevent hepatitis B virus reinfection after liver transplant<ref>{{cite journal | vauthors = Fung J, Cheung C, Chan SC, Yuen MF, Chok KS, Sharr W, Dai WC, Chan AC, Cheung TT, Tsang S, Lam B, Lai CL, Lo CM | title = Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation | journal = Gastroenterology | volume = 141 | issue = 4 | pages = 1212–1219 | date = October 2011 | pmid = 21762659 | doi = 10.1053/j.gastro.2011.06.083 | doi-access = free }}</ref> and to treat HIV patients infected with hepatitis B virus. Entecavir is weakly active against HIV, but is not recommended for use in HIV-HBV co-infected patients without a fully suppressive anti-HIV regimen<ref>{{cite web|title=Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents|url=http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf|publisher=Panel on Antiretroviral Guidelines for Adults and Adolescents|access-date=15 March 2015|url-status=live|archive-url=https://web.archive.org/web/20161101202407/https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf|archive-date=1 November 2016}}</ref> as it may select for resistance to lamivudine and emtricitabine in HIV.<ref>{{cite journal | vauthors = McMahon MA, Jilek BL, Brennan TP, Shen L, Zhou Y, Wind-Rotolo M, Xing S, Bhat S, Hale B, Hegarty R, Chong CR, Liu JO, Siliciano RF, Thio CL | title = The HBV drug entecavir - effects on HIV-1 replication and resistance | journal = The New England Journal of Medicine | volume = 356 | issue = 25 | pages = 2614–2621 | date = June 2007 | pmid = 17582071 | pmc = 3069686 | doi = 10.1056/NEJMoa067710 }}</ref>


The efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Entecavir by mouth is effective and generally well tolerated treatment.<ref name="enteca">{{cite journal | last1 = Scott | first1 = LJ | last2 = Keating | first2 = GM | year = 2009 | title = Entecavir | url = http://adisonline.com/drugs/abstract/2009/69080/Entecavir__A_Review_of_its_Use_in_Chronic.5.aspx | journal = Drugs | volume = 69 | issue = 8 | pages = 1003–1033 | doi = 10.2165/00003495-200969080-00005 | pmid = 19496629 | url-status = dead | archive-url = https://web.archive.org/web/20111008153846/http://adisonline.com/drugs/abstract/2009/69080/Entecavir__A_Review_of_its_Use_in_Chronic.5.aspx | archive-date = 2011-10-08 | access-date = 2010-03-29 }}</ref>
The efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Entecavir by mouth is effective and generally well tolerated treatment.<ref name="enteca">{{cite journal | vauthors = Scott LJ, Keating GM | title = Entecavir: a review of its use in chronic hepatitis B | journal = Drugs | volume = 69 | issue = 8 | pages = 1003–1033 | date = May 2009 | pmid = 19496629 | doi = 10.2165/00003495-200969080-00005 | s2cid = 115493805 | url = http://adisonline.com/drugs/abstract/2009/69080/Entecavir__A_Review_of_its_Use_in_Chronic.5.aspx | url-status = dead | access-date = 29 March 2010 | archive-url = https://web.archive.org/web/20111008153846/http://adisonline.com/drugs/abstract/2009/69080/Entecavir__A_Review_of_its_Use_in_Chronic.5.aspx | archive-date = 8 October 2011 }}</ref>


=== Pregnancy and breastfeeding ===
=== Pregnancy and breastfeeding ===
No adequate and well-controlled studies exist in pregnant women.<ref name="Drugs.com pregnancy" />
It is considered [[pregnancy category]] C in the United States, and currently no adequate and well-controlled studies exist in pregnant women.<ref>{{Cite web|url=https://www.drugs.com/pregnancy/entecavir.html|title=Entecavir (Baraclude) Use During Pregnancy|website=www.drugs.com|access-date=2016-11-07|url-status=live|archive-url=https://web.archive.org/web/20161107162421/https://www.drugs.com/pregnancy/entecavir.html|archive-date=2016-11-07}}</ref>


==Side effects==
==Side effects==
The majority of people who use entecavir have little to no side effects.<ref>{{Cite web|url=https://www.drugs.com/cdi/entecavir.html|title=Entecavir: Indications, Side Effects, Warnings - Drugs.com|website=www.drugs.com|access-date=2016-11-10|url-status=live|archive-url=https://web.archive.org/web/20161107161241/https://www.drugs.com/cdi/entecavir.html|archive-date=2016-11-07}}</ref> The most common side effects include headache, fatigue, dizziness, and nausea.<ref name="bmsPI"/> Less common effects include [[insomnia|trouble sleeping]] and gastrointestinal symptoms such as sour stomach, diarrhea, and vomiting.<ref>{{Cite web|url=https://www.drugs.com/sfx/entecavir-side-effects.html|title=Entecavir Side Effects in Detail - Drugs.com|website=www.drugs.com|access-date=2016-11-10|url-status=live|archive-url=https://web.archive.org/web/20161110172702/https://www.drugs.com/sfx/entecavir-side-effects.html|archive-date=2016-11-10}}</ref>
The majority of people who use entecavir have little to no side effects.<ref>{{cite web|url=https://www.drugs.com/cdi/entecavir.html|title=Entecavir: Indications, Side Effects, Warnings - Drugs.com|website=www.drugs.com|access-date=10 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161107161241/https://www.drugs.com/cdi/entecavir.html|archive-date=7 November 2016}}</ref> The most common side effects include headache, fatigue, dizziness, and nausea.<ref name="Baraclude FDA label"/> Less common effects include [[insomnia|trouble sleeping]] and gastrointestinal symptoms such as sour stomach, diarrhea, and vomiting.<ref>{{cite web|url=https://www.drugs.com/sfx/entecavir-side-effects.html|title=Entecavir Side Effects in Detail - Drugs.com|website=www.drugs.com|access-date=10 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161110172702/https://www.drugs.com/sfx/entecavir-side-effects.html|archive-date=10 November 2016}}</ref>


Serious side effects from entecavir include lactic acidosis, [[hepatotoxicity|liver problems]], [[hepatomegaly|liver enlargement]], and [[steatosis|fat in the liver]].<ref name=Daily2016/>
Serious side effects from entecavir include lactic acidosis, [[hepatotoxicity|liver problems]], [[hepatomegaly|liver enlargement]], and [[steatosis|fat in the liver]].<ref name="Baraclude FDA label" />


Laboratory tests may show an increase in [[alanine transaminase]] (ALT), [[hematuria]], [[glycosuria]], and an increase in [[lipase]].<ref>{{Cite web|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20|title=DailyMed - BARACLUDE- entecavir tablet, film coated BARACLUDE- entecavir solution|website=dailymed.nlm.nih.gov|access-date=2016-11-10|url-status=live|archive-url=https://web.archive.org/web/20161109220804/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20|archive-date=2016-11-09}}</ref> Periodic monitoring of hepatic function and hematology are recommended.<ref name="bmsPI" />
Laboratory tests may show an increase in [[alanine transaminase]] (ALT), [[hematuria]], [[glycosuria]], and an increase in [[lipase]].<ref name="Baraclude FDA label" /> Periodic monitoring of hepatic function and hematology are recommended.<ref name="Baraclude FDA label" />


==Mechanism of action==
==Mechanism of action==
Entecavir is a [[nucleoside analog]],<ref name="pmid17125436">{{cite journal|vauthors=Sims KA, Woodland AM |title=Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection |journal=[[Pharmacother.|Pharmacotherapy]] |volume=26 |issue=12 |pages=1745–57 |date=December 2006 |pmid=17125436 |doi=10.1592/phco.26.12.1745 |s2cid=13149070 }}{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }}{{Closed access}}</ref> or more specifically, a [[deoxyguanosine]] [[analogue (chemical)|analogue]] that belongs to a class of [[carbocyclic nucleoside]]s and inhibits [[reverse transcription]], [[DNA replication]] and [[Transcription (genetics)|transcription]] in the [[viral replication]] process. Other nucleoside and nucleotide analogues include [[lamivudine]], [[telbivudine]], [[adefovir dipivoxil]], and [[tenofovir]].
Entecavir is a [[nucleoside analog]],<ref name="pmid17125436">{{cite journal | vauthors = Sims KA, Woodland AM | title = Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection | journal = Pharmacotherapy | volume = 26 | issue = 12 | pages = 1745–1757 | date = December 2006 | pmid = 17125436 | doi = 10.1592/phco.26.12.1745 | s2cid = 13149070 | doi-access = free }}</ref> or more specifically, a [[deoxyguanosine]] [[analogue (chemical)|analogue]] that belongs to a class of [[carbocyclic nucleoside]]s and inhibits [[reverse transcription]], [[DNA replication]] and [[Transcription (genetics)|transcription]] in the [[viral replication]] process. Other nucleoside and nucleotide analogues include [[lamivudine]], [[telbivudine]], [[adefovir dipivoxil]], and [[tenofovir]].


Entecavir reduces the amount of HBV in the blood by reducing its ability to multiply and infect new cells.<ref>{{Cite web|url=https://www.drugs.com/cdi/entecavir.html|title=Entecavir: Indications, Side Effects, Warnings - Drugs.com|website=www.drugs.com|access-date=2016-11-07|url-status=live|archive-url=https://web.archive.org/web/20161107161241/https://www.drugs.com/cdi/entecavir.html|archive-date=2016-11-07}}</ref>
Entecavir reduces the amount of hepatitis B virus in the blood by reducing its ability to multiply and infect new cells.<ref>{{cite web|url=https://www.drugs.com/cdi/entecavir.html|title=Entecavir: Indications, Side Effects, Warnings - Drugs.com|website=www.drugs.com|access-date=7 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161107161241/https://www.drugs.com/cdi/entecavir.html|archive-date=7 November 2016}}</ref>


==Administration==
==Administration==
Entecavir is taken by mouth as a tablet or solution. Doses are based on a person's weight.<ref name=Daily2016>{{Cite web|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20#section-2.3|title=DailyMed - BARACLUDE- entecavir tablet, film coated BARACLUDE- entecavir solution|website=dailymed.nlm.nih.gov|access-date=2016-11-09|url-status=live|archive-url=https://web.archive.org/web/20161108140245/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20#section-2.3|archive-date=2016-11-08}}</ref> The solution is recommended for children more than 2 years old who weigh up to 30&nbsp;kg. Entecavir is recommended on an empty stomach at least 2 hours before or after a meal, generally at the same time every day. It is not used in children less than 2 years old. Dose adjustments are also recommended for people with decreased kidney function.<ref name=Daily2016/>
Entecavir is taken by mouth as a tablet or solution. Doses are based on a person's weight.<ref name="Baraclude FDA label" /> The solution is recommended for children more than 2 years old who weigh up to 30&nbsp;kg. Entecavir is recommended on an empty stomach at least 2 hours before or after a meal, generally at the same time every day. It is not used in children less than 2 years old. Dose adjustments are also recommended for people with decreased kidney function.<ref name="Baraclude FDA label" />


==History==
==History==
* 1992: SQ-34676 at Squibb as part of anti-herpes virus program<ref>Slusarchyk, W. A., A. K. Field, J. A. Greytok, P. Taunk, A. V. Tooumari, M. G. Young, and R. Zahler. 4-Hydroxy-3-(hydroxymethyl)-2-methylcyclopentyl purines and pyrimidines, a novel class of anti-herpesvirus agents. Abstract from the Fifth International Conference on Antiviral Research. Antivir Res 1992.17(Suppl. 1):98</ref>
* 1992: SQ-34676 at Squibb as part of anti-herpes virus program<ref>{{cite journal | vauthors=Slusarchyk, WA, Field AK, Greytok JA, Taunk P, Tooumari AV, Young MG, Zahler R | title=4-Hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl purines and pyrimidines, a new class of anti-herpesvirus agents | journal=Antiviral Research | volume=17 | year=1992 | doi=10.1016/0166-3542(92)90200-o | page=98}}</ref>
* 1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against HBV, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza<ref name="Bisacchi, G. S. 1997">{{cite journal | last1 = Bisacchi | first1 = G. S. | last2 = Chao | first2 = S. T. | last3 = Bachard | first3 = C. | last4 = Daris | first4 = J. P. | last5 = Innaimo | first5 = S. F. | last6 = Jacobs | first6 = J. A. | last7 = Kocy | first7 = O. | last8 = Lapointe | first8 = P. | last9 = Martel | first9 = A. | last10 = Merchant | first10 = Z. | last11 = Slusarchyk | first11 = W. A. | last12 = Sundeen | first12 = J. E. | last13 = Young | first13 = M. G. | last14 = Colonno | first14 = R. | last15 = Zahler | first15 = R. | year = 1997 | title = BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro | journal = Bioorg. Med. Chem. Lett. | volume = 7 | issue = 2| pages = 127–132 | doi=10.1016/s0960-894x(96)00594-x}}</ref>
* 1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against hepatitis B virus, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza<ref name="Bisacch_1997">{{cite journal | vauthors = Bisacchi GS, Chao ST, Bachard C, Daris JP, Innaimo SF, Jacobs JA, Kocy O, Lapointe P, Martel A, Merchant Z, Slusarchyk WA, Sundeen JE, Young MG, Colonno R, Zahler R | year = 1997 | title = BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro | journal = Bioorganic & Medicinal Chemistry Letters | volume = 7 | issue = 2| pages = 127–132 | doi=10.1016/s0960-894x(96)00594-x }}</ref>
* Superior activity observed against HBV pushed research towards BMS 200475, its base analogues and its enantiomer against HBV in HepG2.2.15 cell line<ref name="Bisacchi, G. S. 1997" />
* Superior activity observed against hepatitis B virus pushed research towards BMS 200475, its base analogues and its enantiomer against hepatitis B virus in HepG2.2.15 cell line<ref name="Bisacch_1997" />
* Comparison to other NAs, proven more selective potent inhibitor of HBV by virtue of being Guanine NA<ref>{{cite journal | last1 = Innaimo | first1 = S F | last2 = Seifer | first2 = M | last3 = Bisacchi | first3 = G S | last4 = Standring | first4 = D N | last5 = Zahler | first5 = R | last6 = Colonno | first6 = R J | year = 1997 | title = Identification of BMS-200475 as a Potent and Selective Inhibitor of Hepatitis B Virus. Antimicrob | journal = Agents Chemother | volume = 41 | issue = 7| pages = 1444–1448 | doi = 10.1128/AAC.41.7.1444 | pmid = 9210663 | pmc = 163937 }}</ref>
* Comparison to other NAs, proven more selective potent inhibitor of hepatitis B virus by virtue of being Guanine NA<ref>{{cite journal | vauthors = Innaimo SF, Seifer M, Bisacchi GS, Standring DN, Zahler R, Colonno RJ | title = Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus | journal = Antimicrobial Agents and Chemotherapy | volume = 41 | issue = 7 | pages = 1444–1448 | date = July 1997 | pmid = 9210663 | pmc = 163937 | doi = 10.1128/AAC.41.7.1444 }}</ref>
* 1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP<ref>{{cite journal | last1 = Seifer | first1 = M. | last2 = Hamatake | first2 = R. K. | last3 = Colonno | first3 = R. J. | last4 = Standring | first4 = D. N. | year = 1998 | title = In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir. Antimicrob | journal = Agents Chemother | volume = 42 | issue = 12| pages = 3200–3208 | doi = 10.1128/AAC.42.12.3200 | pmid = 9835515 | pmc = 106023 }}</ref>
* 1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP<ref>{{cite journal | vauthors = Seifer M, Hamatake RK, Colonno RJ, Standring DN | title = In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 12 | pages = 3200–3208 | date = December 1998 | pmid = 9835515 | pmc = 106023 | doi = 10.1128/AAC.42.12.3200 }}</ref>
* Metabolic studies showed more efficient phosphorylation to triphosphate active form<ref>{{cite journal | last1 = Yamanaka | first1 = G. | last2 = Wilson | first2 = T. | last3 = Innaimo | first3 = S. | last4 = Bisacchi | first4 = G. S. | last5 = Egli | first5 = P. | last6 = Rinehart | first6 = J. K. | last7 = Zahler | first7 = R. | last8 = Colonno | first8 = R. J. | year = 1999 | title = Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus. Antimicrob | journal = Agents Chemother | volume = 43 | issue = 1| pages = 190–193 | doi = 10.1128/AAC.43.1.190 | pmid = 9869593 | pmc = 89048 | doi-access = free }}</ref>
* Metabolic studies showed more efficient phosphorylation to triphosphate active form<ref>{{cite journal | vauthors = Yamanaka G, Wilson T, Innaimo S, Bisacchi GS, Egli P, Rinehart JK, Zahler R, Colonno RJ | title = Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus | journal = Antimicrobial Agents and Chemotherapy | volume = 43 | issue = 1 | pages = 190–193 | date = January 1999 | pmid = 9869593 | pmc = 89048 | doi = 10.1128/AAC.43.1.190 | doi-access = free }}</ref>
* 3-year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance<ref>{{cite journal | last1 = Colonno | first1 = R. J. | last2 = Genovesi | first2 = E. V. | last3 = Medina | first3 = I. | last4 = Lamb | first4 = L. | last5 = Durham | first5 = S. K. | last6 = Huang | first6 = M. L. | last7 = Corey | first7 = L. | last8 = Littlejohn | first8 = M. | last9 = Locarnini | first9 = S. | last10 = Tennant | first10 = B. C. | last11 = Rose | first11 = B. | last12 = Clark | first12 = J. M. | year = 2001 | title = Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection | journal = J. Infect. Dis. | volume = 184 | issue = 10| pages = 1236–1245 | doi=10.1086/324003| pmid = 11679911 | doi-access = free }}</ref>
* 3-year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance<ref>{{cite journal | vauthors = Colonno RJ, Genovesi EV, Medina I, Lamb L, Durham SK, Huang ML, Corey L, Littlejohn M, Locarnini S, Tennant BC, Rose B, Clark JM | title = Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection | journal = The Journal of Infectious Diseases | volume = 184 | issue = 10 | pages = 1236–1245 | date = November 2001 | pmid = 11679911 | doi = 10.1086/324003 | doi-access = free }}</ref>
* Efficacy # LVD resistant HBV replication in vitro<ref>{{cite journal | last1 = Levine | first1 = S. | last2 = Hernandez | first2 = D. | last3 = Yamanaka | first3 = G. | last4 = Zhang | first4 = S. | last5 = Rose | first5 = R. | last6 = Weinheimer | first6 = S. | last7 = Colonno | first7 = R. J. | year = 2002 | title = Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. Antimicrob | journal = Agents Chemother | volume = 46 | issue = 8| pages = 2525–2532 | doi=10.1128/aac.46.8.2525-2532.2002| pmid = 12121928 | pmc = 127388 }}</ref>
* Efficacy # LVD resistant hepatitis B virus replication in vitro<ref>{{cite journal | vauthors = Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, Weinheimer S, Colonno RJ | title = Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro | journal = Antimicrobial Agents and Chemotherapy | volume = 46 | issue = 8 | pages = 2525–2532 | date = August 2002 | pmid = 12121928 | pmc = 127388 | doi = 10.1128/aac.46.8.2525-2532.2002 }}</ref>
* Superior activity compared to LVD in vivo for both HBeAg+ & HBeAg− patients<ref>{{cite journal | last1 = Chang | first1 = T. T. | year = 2006 | title = A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. | doi = 10.1056/nejmoa051285| pmid = 16525137 | journal = N. Engl. J. Med. | volume = 354 | issue = 10| pages = 1001–1010 }}</ref><ref>{{Cite journal|date=9 March 2006|title=Entecavir versus Lamivudine for Patients with HBeAg-Negative Chronic Hepatitis B|journal=[[N. Engl. J. Med.|The New England Journal of Medicine]]|volume=354|issue=10|pages=1011&ndash;20|doi=10.1056/NEJMoa051287|pmid=16525138|vauthors=Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L|hdl=10722/45018|url=http://hub.hku.hk/bitstream/10722/45018/1/125018.pdf}}</ref>
* Superior activity compared to LVD in vivo for both HBeAg+ & HBeAg− patients<ref>{{cite journal | vauthors = Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D | title = A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B | journal = The New England Journal of Medicine | volume = 354 | issue = 10 | pages = 1001–1010 | date = March 2006 | pmid = 16525137 | doi = 10.1056/nejmoa051285 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L | title = Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B | journal = The New England Journal of Medicine | volume = 354 | issue = 10 | pages = 1011–1020 | date = March 2006 | pmid = 16525138 | doi = 10.1056/NEJMoa051287 | doi-access = free | hdl = 10722/45018 | hdl-access = free }}</ref>
* Efficacy in LVD refractory CHB patients<ref>{{cite journal | last1 = Sherman | first1 = M. | last2 = Yurdaydin | first2 = C. | last3 = Sollano | first3 = J. | last4 = Silva | first4 = M. | last5 = Liaw | first5 = Y. F. | last6 = Cianciara | first6 = J. | last7 = Boron-Kaczmarska | first7 = A. | last8 = Martin | first8 = P. | last9 = Goodman | first9 = Z. | last10 = Colonno | first10 = R. J. | last11 = Cross | first11 = A. | last12 = Denisky | first12 = G. | last13 = Kreter | first13 = B. | last14 = Hindes | first14 = R. | year = 2006 | title = Entecavir for the treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. | journal = Gastroenterology | volume = 130 | issue = 7| pages = 2039–2049 | doi=10.1053/j.gastro.2006.04.007| pmid = 16762627 }}</ref>
* Efficacy in LVD refractory CHB patients<ref>{{cite journal | vauthors = Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, Boron-Kaczmarska A, Martin P, Goodman Z, Colonno R, Cross A, Denisky G, Kreter B, Hindes R | title = Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B | journal = Gastroenterology | volume = 130 | issue = 7 | pages = 2039–2049 | date = June 2006 | pmid = 16762627 | doi = 10.1053/j.gastro.2006.04.007 | doi-access = free }}</ref>
* Entecavir was approved by the U.S. [[Food and Drug Administration]] (FDA) in March 2005.<ref>{{cite web | title=Drug Approval Package: Baraclude (Entecavir) NDA #021797 & 021798 | website=U.S. [[Food and Drug Administration]] (FDA) | date=28 December 2011 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_21798_BaracludeTOC.cfm | access-date=24 January 2021 | archive-date=24 March 2013 | archive-url=https://web.archive.org/web/20130324094415/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_21798_BaracludeTOC.cfm | url-status=live }}</ref>
* Entecavir was approved by the U.S. [[Food and Drug Administration|FDA]] in March 2005.


===Patent information===
===Patent information===
[[Bristol-Myers Squibb]] was the original patent holder for Baraclude, the brand name of entecavir in the US and Canada. The drug patent expiration for Baraclude was in 2015.<ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021797&Product_No=001&table1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=www.accessdata.fda.gov|archive-url=https://web.archive.org/web/20160304084741/http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021797&Product_No=001&table1=OB_Rx|archive-date=4 March 2016|accessdate=2015-08-29}}</ref><ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=021798&Appl_type=N|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=Orange Book|at=Patent and Exclusivity for: N021798|access-date=14 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161115140215/http://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=021798&Appl_type=N|archive-date=15 November 2016}}</ref>
[[Bristol-Myers Squibb]] was the original patent holder for Baraclude, the brand name of entecavir in the US and Canada. The drug patent expiration for Baraclude was in 2015.<ref>{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021797&Product_No=001&table1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=U.S. [[Food and Drug Administration]] (FDA)|archive-url=https://web.archive.org/web/20160304084741/http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021797&Product_No=001&table1=OB_Rx|archive-date=4 March 2016|access-date=29 August 2015|url-status=dead}}</ref><ref>{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=021798&Appl_type=N|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=U.S. [[Food and Drug Administration]] (FDA)|access-date=14 November 2016|url-status=unfit|archive-url=https://web.archive.org/web/20161115140215/http://www.accessdata.fda.gov/scripts/cder/ob/patent_info.cfm?Product_No=001&Appl_No=021798&Appl_type=N|archive-date=15 November 2016}}</ref>
Entecavir patents were a subject of litigation in the USA between [[Bristol-Myers-Squibb Co.]] (the patent owner) and [[Teva Pharmaceuticals USA]] (a generic manufacturer). The lawsuit resulted in a relatively rare in the pharmaceutical field patent invalidation for [[obviousness]], which was affirmed on 12 June 2014 by the [[US Court of Appeals for the Federal Circuit]] (752 F.32d 967).
Entecavir patents were a subject of litigation in the US between [[Bristol Myers Squibb]] (the patent owner) and [[Teva Pharmaceuticals USA]] (a generic manufacturer). The lawsuit resulted in a relatively rare in the pharmaceutical field patent invalidation for [[obviousness]], which was affirmed in June 2014, by the [[US Court of Appeals for the Federal Circuit]] (752 F.32d 967).


On August 26, 2014, [[Teva Pharmaceuticals USA]] gained FDA approval for generic equivalents of Baraclude 0.5&nbsp;mg and 1&nbsp;mg tablets;<ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=202122&TABLE1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=www.accessdata.fda.gov|at=Search results from the "OB_Rx" table for query on "202122."|archive-url=https://web.archive.org/web/20151222125427/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=202122&TABLE1=OB_Rx|archive-date=22 December 2015|accessdate=2015-08-29}}</ref> [[Hetero Labs]] received such approval on August 21, 2015;<ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=205740&TABLE1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=www.accessdata.fda.gov|at=Search results from the "OB_Rx" table for query on "205740."|archive-url=https://web.archive.org/web/20160304060955/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=205740&TABLE1=OB_Rx|archive-date=4 March 2016|accessdate=2015-08-29}}</ref> and [[Aurobindo Pharma]] on August 26, 2015.<ref>{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=206217&TABLE1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=www.accessdata.fda.gov|at=Search results from the "OB_Rx" table for query on "206217."|archive-url=https://web.archive.org/web/20160304053459/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=206217&TABLE1=OB_Rx|archive-date=4 March 2016|accessdate=2015-08-29}}</ref>
In August 2014, [[Teva Pharmaceuticals USA]] gained FDA approval for generic equivalents of Baraclude 0.5&nbsp;mg and 1&nbsp;mg tablets;<ref>{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=202122&TABLE1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=U.S. [[Food and Drug Administration]] (FDA)|at=Search results from the "OB_Rx" table for query on "202122."|archive-url=https://web.archive.org/web/20151222125427/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=202122&TABLE1=OB_Rx|archive-date=22 December 2015|access-date=29 August 2015|url-status=dead}}</ref> [[Hetero Labs]] received such approval on 21 August 2015;<ref>{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=205740&TABLE1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=U.S. [[Food and Drug Administration]] (FDA)|at=Search results from the "OB_Rx" table for query on "205740."|archive-url=https://web.archive.org/web/20160304060955/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=205740&TABLE1=OB_Rx|archive-date=4 March 2016|access-date=29 August 2015|url-status=dead}}</ref> and [[Aurobindo Pharma]] on 26 August 2015.<ref>{{cite web|url=http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=206217&TABLE1=OB_Rx|title=Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations|website=U.S. [[Food and Drug Administration]] (FDA)|at=Search results from the "OB_Rx" table for query on "206217."|archive-url=https://web.archive.org/web/20160304053459/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=206217&TABLE1=OB_Rx|archive-date=4 March 2016|access-date=29 August 2015|url-status=dead}}</ref>


==References==
== References ==
{{reflist}}
{{reflist}}


{{DNA antivirals}}
==External links==
⚫
{{Portal bar | Medicine | Viruses}}
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/entecavir | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Entecavir }}
{{Authority control}}

{{Antivirals}}
⚫
{{portal bar|Medicine}}


[[Category:Bristol-Myers Squibb]]
[[Category:Drugs developed by Bristol Myers Squibb]]
[[Category:Nucleoside analog reverse transcriptase inhibitors]]
[[Category:Nucleoside analog reverse transcriptase inhibitors]]
[[Category:Purines]]
[[Category:Purines]]
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[[Category:Cyclopentanes]]
[[Category:Cyclopentanes]]
[[Category:Alkene derivatives]]
[[Category:Alkene derivatives]]
[[Category:Hydroxymethyl compounds]]

Latest revision as of 10:42, 12 July 2024

Not to be confused with Emtricitabine.

Entecavir
Clinical data
Pronunciation/ɛnˈtɛkəvɪər/ en-TEK-ə-veer
Trade namesBaraclude, others
Other namesETV, BMS-200475-01
AHFS/Drugs.comMonograph
MedlinePlusa605028
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilityn/a (≥70)[3]
Protein binding13% (in vitro)
Metabolismnegligible/nil
Elimination half-life128–149 hours
ExcretionKidney 62–73%
Identifiers
  • 2-Amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1H-purin-6-one
CAS Number
PubChem CID
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ECHA InfoCard100.111.234 Edit this at Wikidata
Chemical and physical data
FormulaC12H15N5O3
Molar mass277.284 g·mol−1
3D model (JSmol)
Melting point220 °C (428 °F) value applies to entecavir monohydrate and is a minimum value[5]
  • C=C1C(CC(C1CO)O)N2C=NC3=C2N=C(NC3=O)N
  • 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 ☒N
  • Key:QDGZDCVAUDNJFG-FXQIFTODSA-N ☒N
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Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection.[6] In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used.[6] Entecavir is taken by mouth as a tablet or solution.[6]

Common side effects include headache, nausea, high blood sugar, and decreased kidney function.[6] Severe side effects include enlargement of the liver, high blood lactate levels, and liver inflammation if the medication is stopped.[6] While there appears to be no harm from use during pregnancy, this use has not been well studied.[1] Entecavir is in the nucleoside reverse transcriptase inhibitors (NRTIs) family of medications.[6][7] It prevents the hepatitis B virus from multiplying by blocking reverse transcriptase.[6]

Entecavir was approved for medical use in 2005.[6] It is on the World Health Organization's List of Essential Medicines.[8] It is available as a generic medication.

Medical uses

[edit]

Entecavir is mainly used to treat chronic hepatitis B infection in adults and children two years and older with active viral replication and evidence of active disease with elevations in liver enzymes.[3] It is also used to prevent hepatitis B virus reinfection after liver transplant[9] and to treat HIV patients infected with hepatitis B virus. Entecavir is weakly active against HIV, but is not recommended for use in HIV-HBV co-infected patients without a fully suppressive anti-HIV regimen[10] as it may select for resistance to lamivudine and emtricitabine in HIV.[11]

The efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Entecavir by mouth is effective and generally well tolerated treatment.[12]

Pregnancy and breastfeeding

[edit]

No adequate and well-controlled studies exist in pregnant women.[1]

Side effects

[edit]

The majority of people who use entecavir have little to no side effects.[13] The most common side effects include headache, fatigue, dizziness, and nausea.[3] Less common effects include trouble sleeping and gastrointestinal symptoms such as sour stomach, diarrhea, and vomiting.[14]

Serious side effects from entecavir include lactic acidosis, liver problems, liver enlargement, and fat in the liver.[3]

Laboratory tests may show an increase in alanine transaminase (ALT), hematuria, glycosuria, and an increase in lipase.[3] Periodic monitoring of hepatic function and hematology are recommended.[3]

Mechanism of action

[edit]

Entecavir is a nucleoside analog,[15] or more specifically, a deoxyguanosine analogue that belongs to a class of carbocyclic nucleosides and inhibits reverse transcription, DNA replication and transcription in the viral replication process. Other nucleoside and nucleotide analogues include lamivudine, telbivudine, adefovir dipivoxil, and tenofovir.

Entecavir reduces the amount of hepatitis B virus in the blood by reducing its ability to multiply and infect new cells.[16]

Administration

[edit]

Entecavir is taken by mouth as a tablet or solution. Doses are based on a person's weight.[3] The solution is recommended for children more than 2 years old who weigh up to 30 kg. Entecavir is recommended on an empty stomach at least 2 hours before or after a meal, generally at the same time every day. It is not used in children less than 2 years old. Dose adjustments are also recommended for people with decreased kidney function.[3]

History

[edit]
  • 1992: SQ-34676 at Squibb as part of anti-herpes virus program[17]
  • 1997: BMS 200475 developed at BMS pharmaceutical research institute as antiviral nucleoside analogue à Activity demonstrated against hepatitis B virus, HSV-1, HCMV, VZV in cell lines & no or little activity against HIV or influenza[18]
  • Superior activity observed against hepatitis B virus pushed research towards BMS 200475, its base analogues and its enantiomer against hepatitis B virus in HepG2.2.15 cell line[18]
  • Comparison to other NAs, proven more selective potent inhibitor of hepatitis B virus by virtue of being Guanine NA[19]
  • 1998: Inhibition of hepadnaviral polymerases was demonstrated in vitro in comparison to a number of NAs-TP[20]
  • Metabolic studies showed more efficient phosphorylation to triphosphate active form[21]
  • 3-year treatment of woodchuck model of CHB à sustained antiviral efficacy and prolonged life spans without detectable emergence of resistance[22]
  • Efficacy # LVD resistant hepatitis B virus replication in vitro[23]
  • Superior activity compared to LVD in vivo for both HBeAg+ & HBeAg− patients[24][25]
  • Efficacy in LVD refractory CHB patients[26]
  • Entecavir was approved by the U.S. Food and Drug Administration (FDA) in March 2005.[27]

Patent information

[edit]

Bristol-Myers Squibb was the original patent holder for Baraclude, the brand name of entecavir in the US and Canada. The drug patent expiration for Baraclude was in 2015.[28][29] Entecavir patents were a subject of litigation in the US between Bristol Myers Squibb (the patent owner) and Teva Pharmaceuticals USA (a generic manufacturer). The lawsuit resulted in a relatively rare in the pharmaceutical field patent invalidation for obviousness, which was affirmed in June 2014, by the US Court of Appeals for the Federal Circuit (752 F.32d 967).

In August 2014, Teva Pharmaceuticals USA gained FDA approval for generic equivalents of Baraclude 0.5 mg and 1 mg tablets;[30] Hetero Labs received such approval on 21 August 2015;[31] and Aurobindo Pharma on 26 August 2015.[32]

References

[edit]
  1. ^ a b c "Entecavir (Baraclude) Use During Pregnancy". Drugs.com. 3 December 2019. Archived from the original on 7 November 2016. Retrieved 24 January 2021.
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ a b c d e f g h i "Baraclude- entecavir tablet, film coated Baraclude- entecavir solution". DailyMed. Archived from the original on 8 November 2016. Retrieved 24 January 2021.
  4. ^ "Baraclude EPAR". European Medicines Agency. 26 June 2006. Archived from the original on 6 March 2024. Retrieved 5 July 2024.
  5. ^ O'Neil MJ (2006). "The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals". The Merck Index (14th ed.). p. 613. ISBN 978-0-911910-00-1.
  6. ^ a b c d e f g h "Entecavir". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 28 November 2016.
  7. ^ Shetty K, Wu GY (2009). Chronic Viral Hepatitis: Diagnosis and Therapeutics. Springer Science & Business Media. p. 34. ISBN 9781597455657.
  8. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  9. ^ Fung J, Cheung C, Chan SC, Yuen MF, Chok KS, Sharr W, et al. (October 2011). "Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation". Gastroenterology. 141 (4): 1212–1219. doi:10.1053/j.gastro.2011.06.083. PMID 21762659.
  10. ^ "Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents" (PDF). Panel on Antiretroviral Guidelines for Adults and Adolescents. Archived (PDF) from the original on 1 November 2016. Retrieved 15 March 2015.
  11. ^ McMahon MA, Jilek BL, Brennan TP, Shen L, Zhou Y, Wind-Rotolo M, et al. (June 2007). "The HBV drug entecavir - effects on HIV-1 replication and resistance". The New England Journal of Medicine. 356 (25): 2614–2621. doi:10.1056/NEJMoa067710. PMC 3069686. PMID 17582071.
  12. ^ Scott LJ, Keating GM (May 2009). "Entecavir: a review of its use in chronic hepatitis B". Drugs. 69 (8): 1003–1033. doi:10.2165/00003495-200969080-00005. PMID 19496629. S2CID 115493805. Archived from the original on 8 October 2011. Retrieved 29 March 2010.
  13. ^ "Entecavir: Indications, Side Effects, Warnings - Drugs.com". www.drugs.com. Archived from the original on 7 November 2016. Retrieved 10 November 2016.
  14. ^ "Entecavir Side Effects in Detail - Drugs.com". www.drugs.com. Archived from the original on 10 November 2016. Retrieved 10 November 2016.
  15. ^ Sims KA, Woodland AM (December 2006). "Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection". Pharmacotherapy. 26 (12): 1745–1757. doi:10.1592/phco.26.12.1745. PMID 17125436. S2CID 13149070.
  16. ^ "Entecavir: Indications, Side Effects, Warnings - Drugs.com". www.drugs.com. Archived from the original on 7 November 2016. Retrieved 7 November 2016.
  17. ^ Slusarchyk, WA, Field AK, Greytok JA, Taunk P, Tooumari AV, et al. (1992). "4-Hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl purines and pyrimidines, a new class of anti-herpesvirus agents". Antiviral Research. 17: 98. doi:10.1016/0166-3542(92)90200-o.
  18. ^ a b Bisacchi GS, Chao ST, Bachard C, Daris JP, Innaimo SF, Jacobs JA, et al. (1997). "BMS-200475, a novel carbocyclic 29-deoxyguanosine analog with potent and selective antihepatitis B virus activity in vitro". Bioorganic & Medicinal Chemistry Letters. 7 (2): 127–132. doi:10.1016/s0960-894x(96)00594-x.
  19. ^ Innaimo SF, Seifer M, Bisacchi GS, Standring DN, Zahler R, Colonno RJ (July 1997). "Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus". Antimicrobial Agents and Chemotherapy. 41 (7): 1444–1448. doi:10.1128/AAC.41.7.1444. PMC 163937. PMID 9210663.
  20. ^ Seifer M, Hamatake RK, Colonno RJ, Standring DN (December 1998). "In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir". Antimicrobial Agents and Chemotherapy. 42 (12): 3200–3208. doi:10.1128/AAC.42.12.3200. PMC 106023. PMID 9835515.
  21. ^ Yamanaka G, Wilson T, Innaimo S, Bisacchi GS, Egli P, Rinehart JK, et al. (January 1999). "Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus". Antimicrobial Agents and Chemotherapy. 43 (1): 190–193. doi:10.1128/AAC.43.1.190. PMC 89048. PMID 9869593.
  22. ^ Colonno RJ, Genovesi EV, Medina I, Lamb L, Durham SK, Huang ML, et al. (November 2001). "Long-term entecavir treatment results in sustained antiviral efficacy and prolonged life span in the woodchuck model of chronic hepatitis infection". The Journal of Infectious Diseases. 184 (10): 1236–1245. doi:10.1086/324003. PMID 11679911.
  23. ^ Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, Weinheimer S, et al. (August 2002). "Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro". Antimicrobial Agents and Chemotherapy. 46 (8): 2525–2532. doi:10.1128/aac.46.8.2525-2532.2002. PMC 127388. PMID 12121928.
  24. ^ Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, et al. (March 2006). "A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B". The New England Journal of Medicine. 354 (10): 1001–1010. doi:10.1056/nejmoa051285. PMID 16525137.
  25. ^ Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, et al. (March 2006). "Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B". The New England Journal of Medicine. 354 (10): 1011–1020. doi:10.1056/NEJMoa051287. hdl:10722/45018. PMID 16525138.
  26. ^ Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, et al. (June 2006). "Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B". Gastroenterology. 130 (7): 2039–2049. doi:10.1053/j.gastro.2006.04.007. PMID 16762627.
  27. ^ "Drug Approval Package: Baraclude (Entecavir) NDA #021797 & 021798". U.S. Food and Drug Administration (FDA). 28 December 2011. Archived from the original on 24 March 2013. Retrieved 24 January 2021.
  28. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Archived from the original on 4 March 2016. Retrieved 29 August 2015.
  29. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Archived from the original on 15 November 2016. Retrieved 14 November 2016.
  30. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Search results from the "OB_Rx" table for query on "202122.". Archived from the original on 22 December 2015. Retrieved 29 August 2015.
  31. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Search results from the "OB_Rx" table for query on "205740.". Archived from the original on 4 March 2016. Retrieved 29 August 2015.
  32. ^ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Search results from the "OB_Rx" table for query on "206217.". Archived from the original on 4 March 2016. Retrieved 29 August 2015.
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