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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/733654/2013

EMEA/H/C/002753

EPAR summary for the public

Tivicay

dolutegravir

This is a summary of the European public assessment report (EPAR) for Tivicay. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Tivicay.

For practical information about using Tivicay, patients should read the package leaflet or contact their doctor or pharmacist.

What is Tivicay and what is it used for?

Tivicay is an antiviral medicine containing the active substance dolutegravir. It is used together with other medicines to treat adults and adolescents from 12 years of age who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).

How is Tivicay used?

Tivicay can only be obtained with a prescription and should be prescribed by a doctor who is experienced in managing HIV infection.

Tivicay is available as tablets (50 mg). The dose depends on whether the infection is known or suspected to be resistant to medicines of the class to which Tivicay belongs (integrase inhibitors).

•    In patients whose virus is not resistant to integrase inhibitors, the usual dose is one tablet a day; however, when given with certain medicines that decrease the effectiveness of Tivicay the dose is increased to one tablet twice a day.

•    The dose is one tablet twice a day in patients whose virus is known or suspected to be resistant to integrase inhibitors; in these patients, giving Tivicay with medicines that decrease its effectiveness should be avoided.

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Although Tivicay can normally be taken with or without food, patients whose virus is resistant to this class of medicines should take Tivicay with food as it helps the medicine to get absorbed.

For further information, see the package leaflet.

How does Tivicay work?

The active substance in Tivicay, dolutegravir, is an integrase inhibitor. This is an antiviral medicine that blocks an enzyme called integrase that is needed by the HIV virus to make new copies of itself in the body. When it is given with other medicines, Tivicay helps to prevent the spread of HIV and keep the amount of the virus in the blood at a low level. Tivicay 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.

What benefits of Tivicay have been shown in studies?

Tivicay was demonstrated to be effective against HIV-1 in four main studies. The main measure of effectiveness in all the studies was the response rate, which was the proportion of patients with a reduction of the levels of virus (viral load) in the blood to fewer than 50 copies of HIV-1 RNA per ml.

Two studies involved patients who had not previously been treated for HIV:

•    In the first of these, involving 822 patients, Tivicay once daily was compared with raltegravir (another integrase inhibitor), both given in combination with two other HIV medicines of a different class (known as nucleoside reverse transcriptase inhibitors or NRTIs): 88% (361 of 411 patients) given Tivicay and 85% (351 of 411) given raltegravir responded after 48 weeks of treatment.

•    The second study involved 833 patients given either a combination of Tivicay with two NRTIs or a different three-drug combination (Atripla) that did not include an integrase inhibitor. The response rate at 48 weeks was 88% (364 of 414 patients) in those given Tivicay-based treatment compared with 81% (338 of 419 patients) in those given Atripla.

Two other studies looked at the effectiveness of Tivicay in patients whose previous HIV treatment had stopped working:

•    The first of these involved 715 patients whose previous treatment had not included an integrase inhibitor and whose infection was therefore not expected to be resistant to this class of medicines. Patients were treated with a combination of HIV medicines that included either Tivicay or raltegravir. Response rate at 48 weeks was 71% in patients given treatment based on Tivicay, and 64% in those given treatment based on raltegravir.

•    The second study in previously treated patients involved 183 patients with infection resistant to previous treatment that had involved an integrase inhibitor (i.e. their infection was resistant to several classes of medicine, including previous integrase inhibitors): adding Tivicay twice daily to other treatment resulted in a response rate of 69% after 24 weeks of therapy.

What are the risks associated with Tivicay?

The most common side effects with Tivicay (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea, and headache. More serious adverse effects that have been reported include an uncommon but severe hypersensitivity (allergic) reaction with rash and possible effects on the liver. For the full list of all side effects reported with Tivicay, see the package leaflet.

Tivicay must not be given together with dofetilide, a medicine for disturbances of heart rhythm, as it may cause serious side effects. In addition, the dose of Tivicay may need to be adjusted if certain medicines are taken at the same time. For the full list of restrictions, see the package leaflet.

Why is Tivicay approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Tivicay's benefits are greater than its risks and recommended that it be approved for use in the EU. The Committee concluded that the medicine had demonstrated its effectiveness in both untreated and previously treated patients, including those with resistance to integrase inhibitors. The medicine was generally well tolerated, although the CHMP noted the possible risk of infrequent but severe hypersensitivity reactions.

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

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

Other information about Tivicay

The European Commission granted a marketing authorisation valid throughout the European Union for Tivicay on 16 January 2014.

The full EPAR and risk management plan summary for Tivicay 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 Tivicay, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 01-2014.

Tivicay

EMA/733654/2013

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