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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/355543/2016

EMEA/H/C/000494

EPAR summary for the public

Reyataz

atazanavir

This document is a summary of the European Public Assessment Report (EPAR) for Reyataz. 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 Reyataz.

What is Reyataz?

Reyataz is an antiviral medicine that contains the active substance atazanavir. It is available as capsules (100 mg, 150 mg, 200 mg and 300 mg) and oral powder (50 mg).

What is Reyataz used for?

Reyataz is used together with low-dose ritonavir and other antiviral medicines to treat adults and children aged 3 months and over and weighing at least 5 kg who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).

For patients who have received HIV medicines before, doctors should prescribe Reyataz only after they have looked at which medicines the patient has taken and carried out tests to establish that the virus is likely to respond to Reyataz. The medicine is not expected to work in patients in whom many medicines in the same class as Reyataz (protease inhibitors) do not work.

The medicine can only be obtained with a prescription.

How is Reyataz used?

Treatment with Reyataz should be started by a doctor who has experience in the treatment of HIV infection.

For adults (aged 18 years or over), the recommended dose is 300 mg once a day. In younger patients, the dose of Reyataz depends on body weight. Reyataz oral powder can be used for children aged at

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least 3 months and weighing at least 5 kg, and for patients who cannot swallow capsules. Each dose must be taken with food.

Reyataz is normally given with ritonavir to boost its action but doctors can consider stopping ritonavir in adults in some specific situations.

How does Reyataz work?

The active substance in Reyataz, atazanavir, is a protease inhibitor. It blocks an enzyme called protease, which is needed for the virus to multiply. Blocking the enzyme prevents the virus from multiplying, slowing down the spread of infection. A small dose of another medicine, ritonavir, is normally given at the same time as a 'booster'. Ritonavir slows down the break-down of atazanavir, increasing the levels of atazanavir in the blood. This allows a lower dose of atazanavir to be used for the same antiviral effect. Reyataz, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Reyataz 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.

How has Reyataz been studied?

Reyataz capsules have been assessed in four main studies involving patients aged 16 years and over. One study compared ritonavir-boosted Reyataz with ritonavir-boosted lopinavir (another antiviral medicine) in 883 patients who had not taken treatment for HIV infection before. The other three studies involved a total of 743 patients who had taken treatment for HIV infection before: the first two compared Reyataz, taken with saquinavir (another antiviral medicine) but without ritonavir, with ritonavir-boosted saquinavir or ritonavir-boosted lopinavir. The final study compared Reyataz plus either ritonavir or saquinavir with ritonavir-boosted lopinavir in 358 patients. The main measure of effectiveness was the change in the levels of HIV in the patients' blood (viral load).

Reyataz capsules boosted with ritonavir have also been studied in 41 patients aged between 6 and 18 years. More than half of these patients had taken HIV treatment in the past. The study looked at the effect of the medicine on viral load and on the immune system, among other measures.

A further main study involved 172 patients who had achieved undetectable viral load (below 50 copies/ml) after treatment with Reyataz capsules and ritonavir. It compared continued treatment with either a higher dose of Reyataz without ritonavir or the boosted combination.

Reyataz oral powder with ritonavir has been assessed in two main studies involving 155 children aged from 3 months up to 11 years. More than half of these patients had taken HIV treatment in the past. A measure of effectiveness was the viral load after treatment for 48 weeks.

In all of the studies, the patients also took two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs, a type of antiviral medicine).

What benefit has Reyataz shown during the studies?

In patients who had not been treated before, ritonavir-boosted Reyataz capsules were as effective as ritonavir-boosted lopinavir. At the start of the study, the patients' viral loads were around 88,100 copies/ml, but after 48 weeks, 78% of the patients taking Reyataz (343 out of 440) had viral loads below 50 copies/ml, compared with 76% of those taking lopinavir (338 out of 443).

In patients who had been treated before, the results of the first study could not be interpreted, as a large number of patients left the study before its planned end. In the second study, ritonavir-boosted lopinavir caused a greater reduction in viral load than Reyataz capsules taken without ritonavir after 24 weeks. In the third study, patients taking ritonavir-boosted Reyataz capsules had similar falls in viral load after 24 and 48 weeks as those taking ritonavir-boosted lopinavir: they had fallen by around 99% after 48 weeks. This finding was maintained after 96 weeks.

In the patients aged between 6 and 18 years, 81% of those who had not taken HIV treatment in the past (13 out of 16) and 24% of those who had taken it in the past (6 out of 25) had viral loads below 50 copies/ml after 48 weeks. The patients also had improvements in their immune systems.

In the study in patients who already had undetectable viral loads with ritonavir-boosted Reyataz capsules, these were maintained in 68 of 87 patients (78%) who continued treatment with a higher dose of Reyataz without ritonavir, and in 64 of 85 (75%) who continued with the boosted combination.

In the two studies in children aged from 3 months up to 11 years taking boosted Reyataz oral powder, the viral load was undetectable in about half the children after treatment for 48 weeks.

What is the risk associated with Reyataz?

In adults, the most common side effects with Reyataz (seen in between 1 and 10 patients in 100) are headache, ocular icterus (yellowing of the eyes), vomiting, diarrhoea, abdominal pain (stomach ache), nausea (feeling sick), dyspepsia (heartburn), rash, fatigue (tiredness) and jaundice (yellowing of the skin and eyes because of liver problems). In studies, side effects were similar in younger patients. For the full list of all side effects reported with Reyataz, see the package leaflet.

Reyataz must not be used in patients who have severe reductions in their liver function; if given with ritonavir it must not be used in patients with moderate reduction in liver function. In addition, Reyataz must not be given to patients taking rifampicin (used to treat tuberculosis), sildenafil (when this medicine is used to treat pulmonary arterial hypertension), St John's wort (a herbal medicine used to treat depression) or medicines that are broken down in the body in the same way as Reyataz and are harmful at high levels in the blood. For the full list of restrictions with Reyataz see the package leaflet.

Why has Reyataz been approved?

The CHMP considered that Reyataz's effectiveness had been shown in patients aged at least 3 months and weighing at least 5 kg. The Committee decided that Reyataz's benefits are greater than its risks and recommended that it be given marketing authorisation.

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

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Reyataz have been included in the summary of product characteristics and the package leaflet.

Other information about Reyataz:

The European Commission granted a marketing authorisation valid throughout the European Union for Reyataz on 2 March 2004.

The full EPAR for Reyataz 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 Reyataz, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2016.

Reyataz

EMA/464689/2016

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