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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/588555/2013

EMEA/H/C/000419

EPAR summary for the public

Viread

tenofovir disoproxil

This document 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). Viread is used in combination with other 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 (compensated liver disease). In adults, it can also be used for those patients with liver damage whose liver is not working properly (decompensated liver disease) and those patients who do not respond to treatment with lamivudine (another HIV medicine).

The medicine can only be obtained with a prescription.

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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. Viread is taken once a day with food. The dose may need to be reduced or the medicine given less often in patients who have moderately or severely reduced kidney function. For more information on how the medicine is taken including doses 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. One study carried out in 87 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 fourth study, involving 280 adults who had not responded to treatment with lamivudine, compared Viread alone with 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 levels of 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 of Viread and emtricitabine was 88%. In the fourth study in adults who had not responded to lamivudine treatment, Viread was effective when given alone: 89% of patients taking Viread had a viral level below 400 copies/ml after 96 weeks of treatment, compared with 86% of patients taking the combination treatment of Viread and emtricitabine.

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% of those 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?

A risk management plan has been developed to ensure that Viread 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 Viread, including the appropriate precautions to be followed by healthcare professionals and patients.

The company that makes Viread will also 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.

The full EPAR for Viread 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 Viread, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 10-2013.

Viread