Entecavir

Last updated

Entecavir
Entecavir structure.svg
Entecavir ball-and-stick model.png
Clinical data
Pronunciation /ɛnˈtɛkəvɪər/ en-TEK-ə-veer
Trade names Baraclude, others
Other namesETV, BMS-200475-01
AHFS/Drugs.com Monograph
MedlinePlus a605028
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability n/a (≥70) [3]
Protein binding 13% (in vitro)
Metabolism negligible/nil
Elimination half-life 128–149 hours
Excretion Kidney 62–73%
Identifiers
  • 2-Amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-1H-purin-6-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.111.234 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H15N5O3
Molar mass 277.284 g·mol−1
3D model (JSmol)
Melting point 220 °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 X mark.svgN
  • Key:QDGZDCVAUDNJFG-FXQIFTODSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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]

Contents

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

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

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

Side effects

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

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

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

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. [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]

Related Research Articles

<span class="mw-page-title-main">Hepatitis</span> Inflammation of the liver

Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.

<span class="mw-page-title-main">Antiviral drug</span> Medication used to treat a viral infection

Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.

<span class="mw-page-title-main">Ribavirin</span> Antiviral medication

Ribavirin, also known as tribavirin, is an antiviral medication used to treat illness caused by respiratory syncytial virus (RSV) and hepatitis C virus (HCV) infections, as well as some viral hemorrhagic fevers. For HCV, it is used in combination with other medications, such as simeprevir, sofosbuvir, peginterferon alfa-2b or peginterferon alfa-2a. It can also be used for viral hemorrhagic fevers—specifically, for Lassa fever, Crimean–Congo hemorrhagic fever, and Hantavirus infections. Ribavirin is usually taken orally or inhaled. Despite widespread usage, it has faced scrutiny in the 21st century because of lack of proven efficacy in treating viral infections for which it has been prescribed in the past.

<span class="mw-page-title-main">Zidovudine</span> Antiretroviral medication

Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.

<span class="mw-page-title-main">Viral hepatitis</span> Liver inflammation from a viral infection

Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form, typically progressing from a long-lasting asymptomatic condition up to a decompensated hepatic disease and hepatocellular carcinoma (HCC).

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.

<span class="mw-page-title-main">Lamivudine</span> Chemical compound

Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.

<span class="mw-page-title-main">Tenofovir disoproxil</span> Antiviral drug used to treat or prevent HIV and hepatitis infections

Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.

<span class="mw-page-title-main">Adefovir</span> Chemical compound

Adefovir is a prescription medicine used to treat (chronic) infections with hepatitis B virus. A prodrug form of adefovir was previously called bis-POM PMEA, with trade names Preveon and Hepsera. It is an orally administered nucleotide analog reverse-transcriptase inhibitor (ntRTI). It can be formulated as the pivoxil prodrug adefovir dipivoxil.

<span class="mw-page-title-main">Nucleoside analogue</span> Biochemical compound

Nucleoside analogues are structural analogues of a nucleoside, which normally contain a nucleobase and a sugar. Nucleotide analogues are analogues of a nucleotide, which normally has one to three phosphates linked to a nucleoside. Both types of compounds can deviate from what they mimick in a number of ways, as changes can be made to any of the constituent parts. They are related to nucleic acid analogues.

<span class="mw-page-title-main">Lamivudine/zidovudine</span> Combination drug for HIV

Lamivudine/zidovudine, sold under the brand name Combivir among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains two antiretroviral medications, lamivudine and zidovudine. It is used together with other antiretrovirals. It is taken by mouth twice a day.

<span class="mw-page-title-main">Nitazoxanide</span> Broad-spectrum antiparasitic and antiviral medication

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Telbivudine</span> Chemical compound

Telbivudine is an antiviral drug used in the treatment of hepatitis B infection. It is marketed by Swiss pharmaceutical company Novartis under the trade names Sebivo and Tyzeka. Clinical trials have shown it to be significantly more effective than lamivudine or adefovir, and less likely to cause resistance. However, HBV signature resistance mutation M204I or L180M+M204V have been associated with Telbivudine resistance.

<span class="mw-page-title-main">Elvucitabine</span> Medication

Elvucitabine is an experimental nucleoside reverse transcriptase inhibitor (NRTI), developed by Achillion Pharmaceuticals, Inc. for the treatment of HIV infection.

<span class="mw-page-title-main">Hepatitis B</span> Human viral infection

Hepatitis B is an infectious disease caused by the hepatitis B virus (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.

<span class="mw-page-title-main">Elbasvir</span> Chemical compound

Elbasvir is a drug approved by the FDA in January 2016 for the treatment of hepatitis C. It was developed by Merck and completed Phase III trials, used in combination with the NS3/4A protease inhibitor grazoprevir under the trade name Zepatier, either with or without ribavirin.

Elbasvir/grazoprevir, sold under the brand name Zepatier, is a fixed-dose combination for the treatment of hepatitis C, containing elbasvir and grazoprevir. It is used to treat chronic hepatitis C virus (HCV) genotypes 1 or 4 infection in both treatment-naïve and treatment-experienced patients.

<span class="mw-page-title-main">NS5B inhibitor</span> Class of pharmaceutical drugs

Non-structural protein 5B (NS5B) inhibitors are a class of direct-acting antivirals widely used in the treatment of chronic hepatitis C. Depending on site of action and chemical composition, NS5B inhibitors may be categorized into three classes—nucleoside active site inhibitors (NIs), non-nucleoside allosteric inhibitors, and pyrophosphate analogues. Subsequently, all three classes are then subclassified. All inhibit RNA synthesis by NS5B but at different stages/sites resulting in inability of viral RNA replication. Expression of direct-acting NS5B inhibitors does not take place in cells that are not infected by hepatitis C virus, which seems to be beneficial for this class of drugs.

<span class="mw-page-title-main">Lobucavir</span> Chemical compound

Lobucavir is an antiviral drug that shows broad-spectrum activity against herpesviruses, hepatitis B and other hepadnaviruses, HIV/AIDS and cytomegalovirus. It initially demonstrated positive results in human clinical trials against hepatitis B with minimal adverse effects but was discontinued from further development following the discovery of increased risk of cancer associated with long-term use in mice. Although this carcinogenic risk is present in other antiviral drugs, such as zidovudine and ganciclovir that have been approved for clinical use, development was halted by Bristol-Myers Squibb, its manufacturer.

References

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  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.
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  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.
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  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. 1 2 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.
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