Entecavir

Entecavir is an oral prescription antiviral medication used in the treatment of chronic hepatitis B. Entecavir is in a class of drugs known as nucleoside analogue reverse transcriptase inhibitors. These medicines inhibit the reproduction and spread of the virus by interfering with the DNA replication process.

Other Names

• Baraclude

Uses

Entecavir is used to treat chronic hepatitis B. It also helps prevent the hepatitis B virus from multiplying and infecting new liver cells. Entecavir is also indicated for the treatment of chronic hepatitis B in adults with HIV/AIDS infection. However, entecavir is not active against HIV.

How Entecavir Is Taken

Entecavir comes in tablet and oral suspension forms. The tablets contain 0.5 or 1.0 mg entecavir. The oral solution contains 0.05 mg/ml entecavir in each 260 ml bottle.

Entecavir should be taken on an empty stomach with a full glass of water, at least 2 hours before or 2 hours after eating.

The recommended dosage of entecavir is a single 0.5 mg tablet once-daily for chronic hepatitis B patients beginning treatment for the first time, and a single 1 mg tablet once-daily for patients experiencing resistance to lamivudine. The oral solution and tablet can be used interchangeably.

How It Works

Entecavir is an analog of the DNA and RNA base guanine. The drug inhibits all three steps of viral replication (reverse transcription, DNA replication and transcription).

How the body affects Entecavir

The efficacy of entecavir appears to be proportional to the dose taken. It is well-distributed in the tissues. The absorption of the drug is affected by food, so it should be taken on an empty stomach.

Entecavir is eliminated through the kidneys so the dose may need to be adjusted in patients with kidney disease.

Benefits

Entecavir has been shown to be an effective treatment of hepatitis B through inhibition of virus replication. It is most effective for the treament of non lamivudine-resistant HBV at the 1.0 mg dose. Efficacy appears to be less in lamivudine-resistant HBV treatment. ^[1]

Side Effects

Baraclude may cause lactic acidosis (the build up of lactic acid in the body). Lactic acidosis can start slowly and gradually get worse. Symptoms include:

• Unusual muscle pain and weakness
• Trouble breathing
• Fast or uneven heart rate
• Nausea
• Vomiting
• Stomach pain
• Numbness in the arms or legs

Entecavir may also cause the following symptoms:

• Nausea
• Stomach pain
• Low fever
• Loss of appetite
• Dark urine
• Clay-colored stools
• Jaundice (yellowing of the skin or eyes).

Some people with hepatitis B develop liver symptoms after they stop taking entecavir, even months after stopping. The risk of chronic liver disease, such as cirrhosis and cancer of the liver is unknown and is being studied.

Precautions

Entecavir is not indicated for people suffering from:

• HIV or AIDS
• Kidney disease
• Liver disease or
• Patients that have had a liver transplant

Alternatively, these patients may need a dosage adjustment or special tests during treatment.

Taking entecavir will not prevent the passing hepatitis B to other people through unprotected sex or sharing of needles. It will not cure hepatitis B.

According to the U.S. Food and Drug Administration (FDA), entecavir may be harmful to an unborn baby. It is also not known whether this medication passes into breast milk or if it could harm a nursing baby. ^[2]

Interactions

Entecavir may interact with the following drugs:

• Drugs that weaken the immune system (such as cancer medicine or steroids)
• Amphoteracin B (Fungizone, AmBisome, Amphotec, Abelcet)
• Cyclosporine (Neoral, Sandimmune, Gengraf)
• Pentamidine (Nebupent, Pentam)
• Sirolimus (Rapamune)
• Tacrolimus (Prograf)
• Antibiotics such as capreomycin (Capastat), rifampin ( Rifadin, Rimactane, Rifater), and vancomycin (Vancocin, Vancoled)
• Any other antiviral medicines.
• Medicines that leave the body through the kidneys.

This list is not complete and there may be other drugs that can interact with Baraclude. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors.

History

Entecavir is marketed in the United States by Bristol-Myers Squibb Company as Baraclude. FDA approval for use in the treatment of chronic hepatitis B was granted on March 30, 2005.

Alternatives

The drugs which are currently approved for the treatment of chronic hepatitis B include: conventional interferon (IFN) alpha, lamivudine, adefovir dipivoxil, telbivudine, and entecavir.

Entecavir was found to be more effective than lamivudine in the treatment of hepatitis B. Safety profiles of the two drugs were similar but entecavir did not cause viral resistance in the same way as lamivudine. ^[3]

Telbivudine and adefovir dipivoxil are two other drugs used to treat hepatitis B. Telbivudine appears to be have greater efficacy against the virus. ^[4]

Research

Recent discoveries

• The combination of entecavir and interferon alpha 2b may be an effective treatment for chronic hepatitis B. ^[5]
• An evaluation of the cost-effectiveness of entecavir versus lamivudine in hepatitis BeAg-positive chronic hepatitis B patients. ^[6]
• A study was done to evaluate the efficacy of an entecavir/lamivudine combination to treat HIV and HBV co-infection. ^[7]
• Entecavir and adefovir were compared in the treatment of HBV. ^[8]

Future research

• The use of entecavir to treat patients with hepatitis-B related cirrhosis ^[9]
• Comparing entecavir to adefovir for the treatment of patients with hepatitis B and hepatic decompensation. ^[10]
• A study of the kinetics of entecavir and telbivudine in the treatment of hepatitis B. ^[11]

Clinical Trials

A list of ongoing clinical trials is available from ClinicalTrials.gov: entecavir trials.

References

1. ↑ Dimou E, Papadimitropoulos V, Hadziyannis SJ. The role of entecavir in the treatment of chronic hepatitis B. Ther Clin Risk Manag. 2007 Dec;3(6):1077-86. Abstract | Full Text
2. ↑ U.S. Food and Drug Administration. Barcalude (entecavir)
3. ↑ Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Eng J Med. 2006 Mar 9;354(10):1001-10. Abstract | Full Text
4. ↑ Chan HL, Heathcote EJ, Marcellin P, et al. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Ann Intern Med. 2007 Dec 4;147(11):745-54. Epub 2007 Oct 1. Abstract | Full Text
5. ↑ Ren FY, Jin H, Piao XX, Piao FS. Ribavirin and IFN-alpha combination therapy induces CD4+ T-cell proliferation and Th1 cytokine secretion in patients with chronic hepatitis B. World J Gastroenterol. 2007 Nov 7;13(41):5440-5. Abstract | PDF
6. ↑ J Manag Care Pharm. 2008 Jan-Feb;14(1):21-33. Abstract | PDF
7. ↑ ClinicalTrials.gov. Study of Adding Entecavir to Current Lamivudine Therapy in HIV and HBV Co-Infected Patients
8. ↑ ClinicalTrials.gov. Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection
9. ↑ ClinicalTrials.gov. Entecavir for Patients With Decompensated Hepatitis B Virus (HBV)-Related Cirrhosis
10. ↑ ClinicalTrials.gov. Comparison of Entecavir to Adefovir in Chronic Hepatitis B Virus (HBV) Patients With Hepatic Decompensation
11. ↑ ClinicalTrials.gov. Viral Kinetics Study of Telbivudine and Entecavir in Adults With Chronic Hepatitis B

External Links

MedlinePlus: Entecavir

Centers for Disease Control and Prevention (CDC): Viral Hepatitis B fact sheet