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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/488729/2014

EMEA/H/C/000623

EPAR summary for the public

Baraclude

entecavir

This is a summary of the European public assessment report (EPAR) for Baraclude. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Baraclude.

What is Baraclude?

Baraclude is an antiviral medicine that contains the active substance entecavir. It is available as tablets (0.5 mg and 1 mg) and as an oral solution (0.05 mg/ml).

What is Baraclude used for?

Baraclude is used to treat chronic (long-term) hepatitis B (an infectious disease of the liver, caused by the hepatitis B virus).

It is used in adults with signs of ongoing liver injury (such as inflammation and fibrosis) when the liver is still working properly (compensated liver disease) and also when the liver is no longer working properly (decompensated liver disease).

It can also be considered for children aged from 2 to 18 years but only in those with compensated liver disease.

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 adults with compensated liver disease, the dose depends on whether or not the patient has been previously treated with a medicine in the same group as Baraclude

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(a nucleoside analogue, such as lamivudine). Patients who have not been treated before with a nucleoside analogue receive a 0.5 mg dose, while those who have received lamivudine before but whose infection is no longer responding to it are given a 1 mg dose. The 0.5 mg dose can be taken with or without food, but the 1 mg dose must be taken at least 2 hours before or 2 hours after a meal. The treatment duration is determined by how the patient responds.

The 1 mg daily dose is also used in adults with decompensated liver disease and stopping treatment is not recommended in these patients.

When treatment is considered appropriate in children, the dose depends on their body weight. Children weighing less than 32.6 kg should be given the oral solution, while those weighing 32.6 kg and above can also be given the 0.5 mg tablets. For more information on the use of the medicine in children, see the summary of product characteristics (also part of the EPAR).

How does Baraclude work?

The active substance in Baraclude, entecavir, is an antiviral belonging to the class of the 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 adults 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 whose infection was no longer responding 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 (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.

In a children's study, 180 children aged 2 to 18 years who had chronic hepatitis B were randomly selected to be given either Baraclude or placebo (a dummy treatment). The study looked at the reductions in levels of the virus in the blood and the number of patients who developed antibody to a viral protein (known as e-antigen) and no longer had e-antigen in their blood after 48 weeks of treatment.

What benefit has Baraclude shown during the studies?

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

Baraclude was also shown to be effective in the children's study: 24% of children in the Baraclude group achieved the primary goal of having a viral DNA level of less than 50 IU/ml plus production of antibody to e-antigen and no e-antigen in their blood compared with 2% of children in the placebo group.

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 and restrictions with Baraclude, see the package leaflet.

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.

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. Baraclude has been shown to be effective at suppressing the virus in adults with both compensated and decompensated liver disease. Viral suppression has also been shown in children. The decision to start a child on treatment should be based on careful consideration of their individual needs, as not all children with chronic hepatitis B infection require treatment.

What measures are being taken to ensure the safe and effective use of Baraclude?

A risk management plan has been developed to ensure that Baraclude is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Baraclude, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Baraclude

The European Commission granted a marketing authorisation valid throughout the European Union for Baraclude on 26 June 2006.

The full EPAR for Baraclude can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Baraclude, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 08-2014.

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Baraclude

EMA/488729/2014