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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/169582/2015

EMEA/H/C/000249

EPAR summary for the public

Sustiva

efavirenz

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

What is Sustiva?

Sustiva is an antiviral medicine that contains the active substance efavirenz. It is available as capsules (50, 100, 200 mg) and as tablets (600 mg).

What is Sustiva used for?

Sustiva is used together with other antiviral medicines to treat adults and children aged three months or older and weighing at least 3.5 kg, who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).

The medicine can only be obtained with a prescription.

How is Sustiva used?

Treatment with Sustiva should be started by a doctor who has experience in the management of HIV infection. Sustiva must be given in combination with other antiviral medicines. It is recommended that Sustiva be taken on an empty stomach and without food, preferably at bedtime.

The recommended dose of Sustiva for adults is 600 mg once a day. In patients aged three months to 17 years, the dose depends on body weight. For patients who are unable to swallow, the capsule contents can be mixed with a small amount of food (around two teaspoons). The dose of Sustiva needs to be reduced in patients taking voriconazole (used to treat fungal infections). Patients taking rifampicin (an antibiotic) may need to take a higher dose of Sustiva.

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For full details, see the summary of product characteristics (also part of the EPAR).

How does Sustiva work?

The active substance in Sustiva, efavirenz, is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It works by blocking the activity of reverse transcriptase, an enzyme needed by HIV to produce the genetic instructions for making more viruses once it has infected the cell. By blocking this enzyme, Sustiva, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Sustiva does not cure HIV infection or AIDS, but it can hold off damage to the immune system and avoid the development of infections and diseases associated with AIDS.

How has Sustiva been studied?

Sustiva has been studied in three main studies involving over 1,100 adults:

•    in the first study, Sustiva in combination with lamivudine and zidovudine or with indinavir (other antiviral medicines) was compared with the combination of indinavir, lamivudine and zidovudine;

•    the second study compared Sustiva in combination with nelfinavir and two other antiviral medicines with the same combination without Sustiva;

•    the third study compared adding Sustiva or placebo (a dummy treatment) to a combination of antiviral medicines that included indinavir and two other antiviral medicines, in patients who had already been receiving treatment for HIV infection.

Sustiva has also been studied in 182 patients (of whom 177 were children aged between three months and 18 years) in combination with nelfinavir and other antiviral medicines.

In all of the studies, the main measure of effectiveness was the number of patients who had undetectable levels of HIV 1 in their blood (viral loads) after 24 or 48 weeks of treatment.

What benefit has Sustiva shown during the studies?

All of the studies showed that combinations including Sustiva were at least as effective as the comparator medicines:

•    the first study showed that 67% of the adults treated with Sustiva in combination with zidovudine and lamivudine had viral loads below 400 copies/ml after 48 weeks, compared with 54% of the patients treated with Sustiva and indinavir, and 45% of the patients treated with indinavir, lamivudine and zidovudine;

•    in the second study, Sustiva in combination with nelfinavir was superior to the combination without Sustiva: 70% and 30% of the patients, respectively, had viral loads below 500 copies/ml after 48 weeks;

•    the third study showed that more patients receiving Sustiva had viral loads below 400 copies/ml than those taking placebo after 24 weeks.

Similar results were seen in the studies in children.

What is the risk associated with Sustiva?

The most common side effect with Sustiva (seen in more than 1 patient in 10) is rash. Sustiva is also associated with nervous system symptoms, such as dizziness, headache, somnolence (sleepiness), balance disturbances and impaired concentration, and with psychiatric disorders, including depression, anxiety, insomnia (difficulty sleeping) and abnormal dreams. Taking Sustiva with food may lead to an increase in the frequency of side effects. For a more complete list of side effects reported with Sustiva, see the package leaflet.

Sustiva must not be used in patients with severe liver disease or who are taking any of the following medicines:

•    astemizole, terfenadine (commonly used to treat allergy symptoms - these medicines may be available without prescription);

•    dihydroergotamine, ergotamine, ergonovine, methylergonovine (used to treat migraine headache);

•    midazolam, triazolam (used to relieve anxiety or difficulty sleeping);

•    pimozide (used to treat mental illnesses);

•    cisapride (used to relieve certain stomach problems);

•    bepridil (used to treat angina);

•    St John's wort (a herbal preparation used to treat depression).

Caution is also needed when Sustiva is taken at the same time as other medicines. For the full list of restrictions, see the package leaflet.

Why has Sustiva been approved?

The CHMP decided that Sustiva's benefits are greater than its risks in antiviral combination treatment of HIV-infected adults, adolescents and children three months of age and older. The Committee noted that Sustiva has not been studied adequately in patients with advanced disease (CD4 cell counts below 50 cells/mm3) or after treatment with protease inhibitors (another type of antiviral medicine) that was not working. The Committee also noted that there is little information on the benefits of treatment including a protease inhibitor in patients who have been treated with Sustiva in the past but which stopped working, although there is no evidence to suggest that protease inhibitors may not work in these patients. The Committee recommended that Sustiva be given marketing authorisation.

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

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

Other information about Sustiva

The European Commission granted a marketing authorisation valid throughout the European Union for Sustiva on 28 May 1999.

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

This summary was last updated in 03-2015.

Sustiva

EMA/169582/2015

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