Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Entecavir: Difference between pages

{{Short description|Chemical compound}}

{{Distinguish|Emtricitabine}}

{{Use dmy dates|date=July 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 464189683

| image = Entecavir structure.

| width = 240

| alt =

| image2 = Entecavir ball-and-stick model.png

| alt2 =

| caption =

<!--Clinical data-->

| pronounce = {{IPAc-en|ɛ|n|ˈ|t|ɛ|k|ə|v|ɪər}} {{respell|en|TEK|ə|veer}}

| tradename = Baraclude, others

| =

| 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_category=

| routes_of_administration = [[Oral administration|By mouth]]

| class =

| ATC_prefix = J05

| ATC_suffix = AF10

| ATC_supplemental =

<!-- Legal status -->

| 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_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_comment =

| legal_US_comment = <ref name="Baraclude FDA label" />

| 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-->

| bioavailability =

| protein_bound = 13%

| metabolism =

| metabolites =

| onset =

| duration_of_action =

| excretion = [[Kidney]] 62–73%

<!--Identifiers-->

| = {{cascite||CAS}}

| =

| =

| =

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChemSpiderID_Ref = {{chemspidercite||chemspider}}

| ChemSpiderID =

| UNII_Ref = {{fdacite||FDA}}

| UNII = NNU2O4609D

| ChEBI =

| ChEMBL = 713

| NIAID_ChemDB =

| 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 = 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 =

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = QDGZDCVAUDNJFG-FXQIFTODSA-N

| density =

| density_notes =

| 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 | vauthors = O'Neil MJ }}</ref>

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''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 -->

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 -->

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==

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 | 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 ===

No adequate and well-controlled studies exist in pregnant women.<ref name="Drugs.com pregnancy" />

==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=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="Baraclude FDA label" />

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==

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 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==

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==

* 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 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 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 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 | 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 | 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 | 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 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 | 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 | 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>

===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=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 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&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 ==

{{reflist}}

{{DNA antivirals}}

{{Portal bar | Medicine | Viruses}}

{{Authority control}}

[[Category:Drugs developed by Bristol Myers Squibb]]

[[Category:Nucleoside analog reverse transcriptase inhibitors]]

[[Category:Purines]]

[[Category:Hepatotoxins]]

[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Cyclopentanes]]

[[Category:Alkene derivatives]]

[[Category:Hydroxymethyl compounds]]