Entecavir Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:464189683
Width:240
Tradename:Baraclude, others
Dailymedid:Entecavir
Pregnancy Au:B3
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth
Atc Prefix:J05
Atc Suffix:AF10
Legal Au:S4
Legal Ca:Rx-only
Legal Uk:POM
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Eu Comment:[2]
Legal Status:Rx-only
Bioavailability:n/a (≥70)
Protein Bound:13% (in vitro)
Metabolism:negligible/nil
Elimination Half-Life:128–149 hours
Excretion:Kidney 62–73%
Cas Number:142217-69-4
Pubchem:135398508
Drugbank:DB00442
Chemspiderid:135679
Unii:NNU2O4609D
Kegg:D04008
Chebi:473990
Chembl:713
Synonyms:ETV, BMS-200475-01
Iupac Name:2-Amino-9-[(1''S'',3''R'',4''S'')-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1H-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: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
Stdinchikey:QDGZDCVAUDNJFG-FXQIFTODSA-N
Melting Point:220
Melting Notes:value applies to entecavir monohydrate and is a minimum value[3]

Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection. In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used. Entecavir is taken by mouth as a tablet or solution.

Common side effects include headache, nausea, high blood sugar, and decreased kidney function. Severe side effects include enlargement of the liver, high blood lactate levels, and liver inflammation if the medication is stopped. While there appears to be no harm from use during pregnancy, this use has not been well studied. Entecavir is in the nucleoside reverse transcriptase inhibitors (NRTIs) family of medications.[4] It prevents the hepatitis B virus from multiplying by blocking reverse transcriptase.

Entecavir was approved for medical use in 2005.[5] It is on the World Health Organization's List of Essential Medicines.[6] 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.[7] It is also used to prevent hepatitis B virus reinfection after liver transplant[8] 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[9] as it may select for resistance to lamivudine and emtricitabine in HIV.[10]

The efficacy of entecavir has been studied in several randomized, double-blind, multicentre trials. Entecavir by mouth is effective and generally well tolerated treatment.[11]

Pregnancy and breastfeeding

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

Side effects

The majority of people who use entecavir have little to no side effects.[12] The most common side effects include headache, fatigue, dizziness, and nausea.[7] Less common effects include trouble sleeping and gastrointestinal symptoms such as sour stomach, diarrhea, and vomiting.[13]

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

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

Mechanism of action

Entecavir is a nucleoside analog,[14] 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.[15]

Administration

Entecavir is taken by mouth as a tablet or solution. Doses are based on a person's weight. 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.

History

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.[27] [28] 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;[29] Hetero Labs received such approval on 21 August 2015;[30] and Aurobindo Pharma on 26 August 2015.[31]

Notes and References

  1. Web site: Entecavir (Baraclude) Use During Pregnancy . Drugs.com . 3 December 2019 . 24 January 2021 . 7 November 2016 . https://web.archive.org/web/20161107162421/https://www.drugs.com/pregnancy/entecavir.html . live .
  2. Web site: European Medicines Agency . Baraclude EPAR . 26 June 2006 . 5 July 2024 . 6 March 2024 . https://web.archive.org/web/20240306150057/https://www.ema.europa.eu/en/medicines/human/EPAR/baraclude . live .
  3. Encyclopedia: The Merck Index . 14th . 2006 . 613 . 978-0-911910-00-1 . The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals . O'Neil MJ .
  4. Book: Shetty K, Wu GY . Chronic Viral Hepatitis: Diagnosis and Therapeutics. 2009. Springer Science & Business Media. 9781597455657. 34. en.
  5. Web site: Entecavir. The American Society of Health-System Pharmacists. 28 November 2016. live. https://web.archive.org/web/20161220224057/https://www.drugs.com/monograph/entecavir.html. 20 December 2016.
  6. Book: ((World Health Organization)) . The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) . 2023 . 10665/371090 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2023.02 . free .
  7. Web site: Baraclude- entecavir tablet, film coated Baraclude- entecavir solution . DailyMed . 24 January 2021 . 8 November 2016 . https://web.archive.org/web/20161108140245/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=046e61c9-9298-4b2e-b76e-b26b81fecd20 . live .
  8. 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 . Entecavir monotherapy is effective in suppressing hepatitis B virus after liver transplantation . Gastroenterology . 141 . 4 . 1212–1219 . October 2011 . 21762659 . 10.1053/j.gastro.2011.06.083 . free .
  9. Web site: Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Panel on Antiretroviral Guidelines for Adults and Adolescents. 15 March 2015. live. https://web.archive.org/web/20161101202407/https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. 1 November 2016.
  10. 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 . The HBV drug entecavir - effects on HIV-1 replication and resistance . The New England Journal of Medicine . 356 . 25 . 2614–2621 . June 2007 . 17582071 . 3069686 . 10.1056/NEJMoa067710 .
  11. Scott LJ, Keating GM . Entecavir: a review of its use in chronic hepatitis B . Drugs . 69 . 8 . 1003–1033 . May 2009 . 19496629 . 10.2165/00003495-200969080-00005 . 115493805 . dead . 29 March 2010 . https://web.archive.org/web/20111008153846/http://adisonline.com/drugs/abstract/2009/69080/Entecavir__A_Review_of_its_Use_in_Chronic.5.aspx . 8 October 2011 .
  12. Web site: Entecavir: Indications, Side Effects, Warnings - Drugs.com. www.drugs.com. 10 November 2016. live. https://web.archive.org/web/20161107161241/https://www.drugs.com/cdi/entecavir.html. 7 November 2016.
  13. Web site: Entecavir Side Effects in Detail - Drugs.com. www.drugs.com. 10 November 2016. live. https://web.archive.org/web/20161110172702/https://www.drugs.com/sfx/entecavir-side-effects.html. 10 November 2016.
  14. Sims KA, Woodland AM . Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection . Pharmacotherapy . 26 . 12 . 1745–1757 . December 2006 . 17125436 . 10.1592/phco.26.12.1745 . 13149070 . free .
  15. Web site: Entecavir: Indications, Side Effects, Warnings - Drugs.com. www.drugs.com. 7 November 2016. live. https://web.archive.org/web/20161107161241/https://www.drugs.com/cdi/entecavir.html. 7 November 2016.
  16. Slusarchyk, WA, Field AK, Greytok JA, Taunk P, Tooumari AV, Young MG, Zahler R . 4-Hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl purines and pyrimidines, a new class of anti-herpesvirus agents . Antiviral Research . 17 . 1992 . 10.1016/0166-3542(92)90200-o . 98.
  17. 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 . 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 . 10.1016/s0960-894x(96)00594-x .
  18. Innaimo SF, Seifer M, Bisacchi GS, Standring DN, Zahler R, Colonno RJ . Identification of BMS-200475 as a potent and selective inhibitor of hepatitis B virus . Antimicrobial Agents and Chemotherapy . 41 . 7 . 1444–1448 . July 1997 . 9210663 . 163937 . 10.1128/AAC.41.7.1444 .
  19. Seifer M, Hamatake RK, Colonno RJ, Standring DN . In vitro inhibition of hepadnavirus polymerases by the triphosphates of BMS-200475 and lobucavir . Antimicrobial Agents and Chemotherapy . 42 . 12 . 3200–3208 . December 1998 . 9835515 . 106023 . 10.1128/AAC.42.12.3200 .
  20. Yamanaka G, Wilson T, Innaimo S, Bisacchi GS, Egli P, Rinehart JK, Zahler R, Colonno RJ . Metabolic studies on BMS-200475, a new antiviral compound active against hepatitis B virus . Antimicrobial Agents and Chemotherapy . 43 . 1 . 190–193 . January 1999 . 9869593 . 89048 . 10.1128/AAC.43.1.190 . free .
  21. Colonno RJ, Genovesi EV, Medina I, Lamb L, Durham SK, Huang ML, Corey L, Littlejohn M, Locarnini S, Tennant BC, Rose B, Clark JM . 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 . November 2001 . 11679911 . 10.1086/324003 . free .
  22. Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, Weinheimer S, Colonno RJ . Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro . Antimicrobial Agents and Chemotherapy . 46 . 8 . 2525–2532 . August 2002 . 12121928 . 127388 . 10.1128/aac.46.8.2525-2532.2002 .
  23. 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 . A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B . The New England Journal of Medicine . 354 . 10 . 1001–1010 . March 2006 . 16525137 . 10.1056/nejmoa051285 . free .
  24. Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L . Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B . The New England Journal of Medicine . 354 . 10 . 1011–1020 . March 2006 . 16525138 . 10.1056/NEJMoa051287 . free . 10722/45018 . free .
  25. 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 . Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B . Gastroenterology . 130 . 7 . 2039–2049 . June 2006 . 16762627 . 10.1053/j.gastro.2006.04.007 . free .
  26. Web site: Drug Approval Package: Baraclude (Entecavir) NDA #021797 & 021798 . U.S. Food and Drug Administration (FDA) . 28 December 2011 . 24 January 2021 . 24 March 2013 . https://web.archive.org/web/20130324094415/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21797_21798_BaracludeTOC.cfm . live .
  27. Web site: Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration (FDA). 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. 4 March 2016. 29 August 2015. dead.
  28. Web site: Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration (FDA). 14 November 2016. unfit. 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. 15 November 2016.
  29. Web site: 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.". https://web.archive.org/web/20151222125427/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=202122&TABLE1=OB_Rx. 22 December 2015. 29 August 2015. dead.
  30. Web site: 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.". https://web.archive.org/web/20160304060955/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=205740&TABLE1=OB_Rx. 4 March 2016. 29 August 2015. dead.
  31. Web site: 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.". https://web.archive.org/web/20160304053459/http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl_No=206217&TABLE1=OB_Rx. 4 March 2016. 29 August 2015. dead.

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