Viread

tenofovir disoproxil fumarate

This is a summary of the European public assessment report (EPAR) for Viread. 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 Viread.

What is Viread?

Viread is a medicine containing the active substance tenofovir disoproxil. It is available as tablets (123, 163, 204 and 245 mg) and as granules (33 mg/g).

What is Viread used for?

Viread is used to treat patients aged two years and above infected with human immunodeficiency virus type 1 (HIV 1), a virus that causes acquired immune deficiency syndrome (AIDS), and is used in combination with other anti-HIV medicines. In children and adolescents its use is only for those who cannot be treated with other first-line nucleotide reverse-transcriptase inhibitors (NRTI). For patients who have taken medicines to treat HIV infection before, doctors should only prescribe Viread once they have looked at the antiviral medicines the patient has taken before or the likelihood of the virus’s response to antiviral medicines.

Viread is also used to treat chronic (long-term) hepatitis-B-virus infection in adults and adolescents aged 12 years and above with liver damage whose liver is still working properly. In adults it can also be used for those patients with liver damage whose liver is not working properly (decompensated liver disease).

The medicine can only be obtained with a prescription.

How is Viread used?

Treatment with Viread should be started by a doctor who has experience in the treatment of HIV infection or chronic hepatitis B. For information on how the medicine is taken including doses and for adults, adolescents and children, see the summary of product characteristics.

How does Viread work?

The active substance in Viread, tenofovir disoproxil, is a ‘prodrug’ that is converted into tenofovir in the body.

Tenofovir is a nucleotide reverse-transcriptase inhibitor (NRTI). In HIV infection, it blocks the activity of reverse transcriptase, an enzyme produced by HIV that allows it to infect cells and make more viruses. Viread, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Viread does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.

Tenofovir also interferes with the action of an enzyme produced by the hepatitis-B virus called ‘DNA polymerase’, which is involved in the formation of viral DNA. Viread stops the virus making DNA and prevents it from multiplying and spreading.

How has Viread been studied?

For the treatment of HIV, three studies involving 1,343 HIV-infected adults investigated the effect of adding Viread to existing treatment or compared Viread with another medicine, stavudine, when taken in combination with lamivudine and efavirenz. Two studies carried out in 177 adolescents (12 to 18 years of age) investigated the effects of adding Viread to existing treatment. A study in 97 children (aged two to twelve years) being treated with stavudine or zidovudine, compared the effects of switching their treatment to Viread with continuing previous treatment. The main measure of effectiveness for all the HIV studies was based on the levels of HIV in the blood (viral load).

For the treatment of hepatitis B, two studies involving 641 adult patients compared Viread with another medicine, adefovir dipivoxil. One of these studies involved patients with ‘HBeAg-negative’ hepatitis B, a type that is more difficult to treat, while the other involved the more common HBeAg-positive’ hepatitis B. A third study involving 112 adults whose liver had stopped working properly (decompensated liver disease) compared Viread with entecavir and a combination treatment of Viread and emtricitabine. A study was also carried in 106 adolescents with either ‘HBeAg-negative’ or ‘HBeAg-positive’ hepatitis B, comparing Viread with placebo (a dummy treatment). These studies looked at the levels of the hepatitis-B virus in the blood after treatment and the reduction in liver damage.

What benefit has Viread shown during the studies?

In HIV-infected adults, adding Viread to existing treatment resulted in a fall in viral load of around 75% after four and after 24 weeks, compared with a small rise or fall in viral load of around 5% in the patients taking placebo. Viread was also as effective as stavudine, with similar numbers of patients in the Viread and stavudine groups having viral loads below 400 copies/ml after 48 weeks.

In adolescents, there was no benefit of adding Viread to existing treatment compared with adding placebo. However, Viread was shown to produce similar levels of the active substance in the body as in adults, and it was judged that the results were influenced by the type of patients included in the Viread group. Results in children showed that the vast majority of those who switched treatment from stavudine or zidovudine maintained their low HIV blood levels on Viread (83% of children in the Viread group and 92% of those on stavudine or zidovudine had viral loads below 400 copies/ml after 48 weeks).

In adults with chronic hepatitis B and compensated liver disease, Viread was more effective than adefovir dipivoxil. After 48 weeks, 71% of the HBeAg-negative and 67% of HBeAg-positive patients taking Viread had a complete response to treatment, compared with 49% and 12%, respectively, of the patients taking adefovir dipivoxil. In the third study in adults with hepatitis B and decompensated liver disease, 70% of patients taking Viread or entecavir had a viral level below 400 copies/ml. The figure for the combination treatment with Viread with emtricitabine was 88%.

In adolescents with chronic hepatitis B, 88% of patients taking Viread had a viral level below 400 copies/ml after 72 weeks compared with 0% taking placebo.

What is the risk associated with Viread?

The most common side effects with Viread (seen in more than 1 patient in 10) are nausea (feeling sick), vomiting, diarrhoea, dizziness, hypophosphataemia (low levels of phosphate in the blood), rash and asthenia (weakness). Rare cases of severe kidney problems have also been seen in patients treated with Viread. Moreover, Viread may cause a reduction in bone density. For the full list of side effects reported with Viread, see the package leaflet.

Viread must not be used in people who are hypersensitive (allergic) to tenofovir, to tenofovir disoproxil fumarate, or to any of the other ingredients.

Why has Viread been approved?

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

What measures are being taken to ensure the safe use of Viread?

The company that makes Viread will ensure that all doctors who are expected to prescribe or use Viread are provided with educational materials containing important safety information, particularly on the risks and precautions relating to kidney function and the bones.

Other information about Viread

The European Commission granted a marketing authorisation valid throughout the European Union for Viread on 5 February 2002.

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

This EPAR was last updated on 13/12/2012 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

31/01/2012  Viread -EMEA/H/C/000419 -X/0105/G

Contents

• Annex I - Summary of product characteristics
• Annex IIA - Manufacturing-authorisation holder responsible for batch release
• Annex IIB - Conditions of the marketing authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmacotherapeutic group

Antivirals for systemic use

Therapeutic indication

Viread 123-mg film-coated tablets are indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1-infected paediatric patients, with nucleoside-reverse-transcriptase-inhibitor (NRTI) resistance or toxicities precluding the use of first line agents, aged 6 to < 12 years who weigh from 17 kg to less than 22 kg.

The choice of Viread to treat antiretroviral-experienced patients with HIV-1 infection should be based on individual viral resistance testing and / or treatment history of patients.

Viread 163-mg film-coated tablets are indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1-infected paediatric patients, with NRTI resistance or toxicities precluding the use of first line agents, aged 6 to < 12 years who weigh from 22 kg to less than 28 kg.

The choice of Viread to treat antiretroviral-experienced patients with HIV-1 infection should be based on individual viral resistance testing and / or treatment history of patients.

Viread 204-mg film-coated tablets are indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected paediatric patients, with NRTI resistance or toxicities precluding the use of first line agents, aged 6 to < 12 years who weigh from 28 kg to less than 35 kg.

The choice of Viread to treat antiretroviral-experienced patients with HIV-1 infection should be based on individual viral resistance testing and / or treatment history of patients.

HIV-1 infection

Viread 245-mg film-coated tablets are indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected adults.

In adults, the demonstration of the benefit of Viread in HIV-1 infection is based on results of one study in treatment-naïve patients, including patients with a high viral load (> 100,000 copies/ml) and studies in which Viread was added to stable background therapy (mainly tritherapy) in antiretroviral pre-treated patients experiencing early virological failure (< 10,000 copies/ml, with the majority of patients having < 5,000 copies/ml).

Viread 245-mg film-coated tablets are also indicated for the treatment of HIV-1 infected adolescents, with NRTI resistance or toxicities precluding the use of first line agents, aged 12 to < 18 years.

The choice of Viread to treat antiretroviral-experienced patients with HIV-1 infection should be based on individual viral resistance testing and/or treatment history of patients.

Hepatitis-B infection

Viread 245-mg film-coated tablets are indicated for the treatment of chronic hepatitis B in adults with:

• compensated liver disease, with evidence of active viral replication, persistently elevated serum alanine aminotransferase (ALT) levels and histological evidence of active inflammation and/or fibrosis (see section 5.1);
• decompensated liver disease (see sections 4.4, 4.8 and 5.1).

Viread 245-mg film-coated tablets are indicated for the treatment of chronic hepatitis B in adolescents 12 to < 18 years of age with:

• compensated liver disease and evidence of immune active disease, i.e. active viral replication, persistently elevated serum ALT levels and histological evidence of active inflammation and / or fibrosis (see sections 4.4, 4.8 and 5.1).

HIV-1 infection

Viread 33-mg/g granules are indicated in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected paediatric patients, with NRTI resistance or toxicities precluding the use of first line agents, from 2 to < 6 years of age, and above 6 years of age for whom a solid dosage form is not…

Changes since initial authorisation of medicine

Initial marketing-authorisation documents