Active Substance: entecavir
Common Name: entecavir
ATC Code: J05AF10
Marketing Authorisation Holder: Bristol-Myers Squibb Pharma EEIG
Active Substance: entecavir
Status: Authorised
Authorisation Date: 2006-06-26
Therapeutic Area: Hepatitis B, Chronic
Pharmacotherapeutic Group: Antivirals for systemic use

Therapeutic Indication

Baraclude is indicated for the treatment of chronic hepatitis-B-virus (HBV) infection in adults with compensated liver disease and evidence of active viral replication, persistently elevated serum alanine-aminotransferase (ALT) levels and histological evidence of active inflammation and / or fibrosis. This indication is based on clinical-trial data in nucleoside-naive patients with HBeAg-positive and HBeAg-negative HBV infection. With respect to patients with lamivudine-refractory hepatitis B, see sections 4.4 and 5.1.

What is Baraclude?

Baraclude contains the active substance entecavir. It is available as tablets (white: 0.5 mg, pink: 1 mg) or as an oral solution (0.05 mg/ml).

What is Baraclude used for?

Baraclude is used to treat adult patients who have chronic (long-term) hepatitis B (disease of the liver due to an infection with the hepatitis-B virus). It is used in patients with:

  • compensated liver disease (when the liver is damaged but functions normally), who also show signs that the virus is still multiplying, and signs of liver damage (raised liver enzyme, signs of damage when liver tissue is examined under a microscope);
  • decompensated liver disease (when the liver does not work normally).

The medicine can only be obtained with a prescription.

How is Baraclude used?

Treatment with Baraclude should be started by a doctor with experience in the management of chronic hepatitis B.

Baraclude is taken once a day. For compensated liver disease, the dose depends on whether or not the patient has been previously treated for chronic hepatitis B with a medicine in the same group as Baraclude (a nucleoside analogue, such as lamivudine). Patients who have not been treated before with a nucleoside analogue receive a 0.5-mg dose, while a 1-mg dose is used in patients who have received lamivudine before, but who are now ‘refractory’ (no longer responding) to lamivudine. The 0.5-mg dose can be taken with or without food, but the 1-mg dose must be taken at least two hours before or two hours after a meal. The treatment duration is determined by how the patient responds.

For decompensated liver disease, the dose is 1 mg, which must be taken at least two hours before or two hours after a meal. In these patients, stopping treatment is not recommended.

Doses are lower for patients who have kidney problems, for whom the oral solution can be used.

How does Baraclude work?

The active substance in Baraclude, entecavir, is an antiviral belonging to the class nucleoside analogues. Entecavir interferes with the action of a viral enzyme, DNA polymerase, which is involved in the formation of viral DNA. Entecavir stops the virus making DNA, and prevents it from multiplying and spreading.

How has Baraclude been studied?

Baraclude was compared with lamivudine in three main studies in patients with chronic hepatitis B who had compensated liver disease. Two of the studies were carried out in 1,363 patients who had not been treated with nucleoside analogues before. The third study was carried out in 293 patients who had become refractory to lamivudine treatment. The studies looked at how the liver damage had evolved after 48 weeks treatment by examining samples of liver tissue and measuring signs of the disease such as the levels of a liver enzyme (alanine transaminase, ALT) or viral DNA in the blood.

Baraclude was also compared with another medicine, adefovir dipivoxil, in 195 patients with chronic hepatitis B with decompensated liver disease. This study looked at the reduction in viral DNA in the blood after 24 weeks.

What benefit has Baraclude shown during the studies?

In patients with compensated liver disease, Baraclude was more effective than lamivudine in patients who had not been treated with nucleoside analogues before: an improvement in the condition of the liver was seen in just over 70% of the patients treated with Baraclude, against just over 60% of the patients treated with lamivudine. Baraclude was also more effective than lamivudine in patients refractory to lamivudine: 55% of patients treated with Baraclude had improvements in the condition of their liver, against 28% of those treated with lamivudine. At the end of the study, 55% of the patients treated with Baraclude had both a normal ALT level and undetectable viral DNA in their blood, while 4% of those treated with lamivudine showed the same results.

In patients with decompensated liver disease, there was a greater reduction in viral DNA with Baraclude than with adefovir dipivoxil.

What is the risk associated with Baraclude?

The most common side effects seen with Baraclude are headache (seen in 9% of patients), fatigue (tiredness, 6%), dizziness (4%) and nausea (feeling sick, 3%). For the full list of side effects reported with Baraclude, see the package leaflet.

Baraclude should not be used in people who may be hypersensitive (allergic) to entecavir or any of the other ingredients.

Patients also need to know that they may also suffer a worsening of their liver disease. This can happen during the treatment, or after it has been stopped. Resistance to entecavir (when a virus becomes insensitive to the antiviral) has been seen in lamivudine-refractory patients. As resistance may have an impact on effectiveness, this will be closely monitored during long-term follow-up.

Why has Baraclude been approved?

The CHMP concluded that Baraclude’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Baraclude

The European Commission granted a marketing authorisation valid throughout the European Union for Baraclude to Bristol-Myers Squibb Pharma EEIG on 26 June 2006. The marketing authorisation is valid for five years, after which it can be renewed.

For more information about treatment with Baraclude, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Source: European Medicines Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.