Prezista

darunavir

This is a summary of the European public assessment report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach its recommendations on how to use the medicine.

If you need more information about your medical condition or your treatment, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis of the CHMP recommendations, read the scientific discussion (also part of the EPAR).

What is Prezista?

Prezista is a medicine that contains the active substance darunavir. It is available as tablets (white and caplet-shaped: 75 mg; white and oval: 150 mg; orange and oval: 300 and 600 mg; light orange and oval: 400 mg).

What is Prezista used for?

Prezista is used together with low-dose ritonavir and other antiviral medicines to treat patients aged six years or over who are infected with human immunodeficiency virus (HIV‑1), a virus that causes acquired immune deficiency syndrome (AIDS). Prezista can be used in adults (over the age of 18 years), whether they have been treated before or not. In children and adolescents aged between six and 18 years, it can only be used if they have been treated before and weigh at least 20 kg.

Doctors should prescribe Prezista to patients who have been treated before only once they have looked at the antiviral medicines that the patient has taken before and checked that the virus causing the infection is likely to respond to the medicine.

The medicine can only be obtained with a prescription.

How is Prezista used?

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

For adults who have not been treated before, the recommended dose is 800 mg once a day. For adults who have been treated before, the dose is 600 mg twice a day. A dose of 800 mg once a day can also be taken, provided that the patients are healthy enough and that the HIV virus causing their infection has been shown to be likely to respond to Prezista. Children and adolescents receive doses that depend on their body weight, and vary between 375 and 600 mg twice a day. Each dose of Prezista must be taken with ritonavir, within 30 minutes of finishing a meal.

How does Prezista work?

The active substance in Prezista, darunavir, is a protease inhibitor. It blocks an enzyme called protease, which is involved in the reproduction of HIV. When the enzyme is blocked, the virus does not reproduce normally, slowing down the rate of replication. Ritonavir is another protease inhibitor that is used as a ‘booster’. It slows down the rate at which darunavir is broken down, increasing the levels of darunavir in the blood. This allows a lower dose of darunavir to be used for the same antiviral effect.

Prezista, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Prezista does not cure HIV infection or AIDS, but it may delay or reverse the damage to the immune system and the development of infections and diseases associated with AIDS.

How has Prezista been studied?

In adults, Prezista has been studied in five main studies. One study compared ritonavir-boosted Prezista 800 mg once a day with ritonavir-boosted lopinavir (another protease inhibitor) in 691 adults who had not been treated for HIV before.

Three studies involved adults who had been treated before who received 600 mg Prezista twice a day. One study compared ritonavir-boosted Prezista with ritonavir-boosted lopinavir in 604 patients who had taken some anti‑HIV medicines in the past. The other two studies compared ritonavir-boosted Prezista with other protease inhibitors chosen on the basis of the patient’s previous treatments and predicted response, in a total of 628 patients who had taken many anti‑HIV medicines in the past.

The fifth study involved 590 adults who had been treated before and compared Prezista 800 mg once a day with Prezista 600 mg twice a day.

Ritonavir-boosted Prezista has also been studied in 80 children and adolescents aged between six and 18 years. All of these patients had been treated before and weighed at least 20 kg.

In all of the studies, the patients also took other anti‑HIV medicines. The main measures of effectiveness were based on the change in HIV levels in the blood (viral load).

What benefit has Prezista shown during the studies?

In adults who had not been treated before, Prezista was as effective as lopinavir. After 48 weeks, 84% of the patients taking ritonavir-boosted Prezista had viral loads below 50 copies/ml (287 out of 343) compared with 78% of those taking ritonavir-boosted lopinavir (271 out of 346).

In adults who had been treated before, those taking Prezista achieved lower viral loads than those taking the comparator protease inhibitors. In patients who had taken some anti-HIV medicines in the past, 77% of those taking ritonavir-boosted Prezista had viral loads below 400 copies/ml after 48 weeks, compared with 68% of those taking ritonavir-boosted lopinavir. In adults who had received many anti-HIV medicines in the past, 70% of those taking the approved dose of ritonavir-boosted Prezista (92 out of 131) had at least a 90% reduction in viral load after 24 weeks, compared with 21% of those taking the comparator protease inhibitors (26 out of 124).

Prezista 800 mg once a day was as effective as Prezista 600 mg twice a day in patients who had been treated before: after 48 weeks, 72% of the patients taking Prezista 800 mg once day had viral loads below 50 copies/ml (212 out of 294) compared with 71% of those taking Prezista 600 mg twice a day (210 out of 296).

Similar results were seen in children and adolescents: 74% (59 out of 80) had at least a 90% reduction in viral loads after 24 weeks of treatment.

What is the risk associated with Prezista?

In adults, the most common side effects with Prezista are diarrhoea, ‘immune reconstitution syndrome’, nausea (feeling sick), pyrexia (fever) and rash. Immune reconstitution syndrome happens when the patient’s immune system starts working again and fights existing infections, causing inflammation at the site of the infection. Side effects are similar in children and adolescents. For the full list of all side effects reported with Prezista, see the package leaflet.

Prezista should not be taken by patients who may be hypersensitive (allergic) to darunavir or any of the other ingredients. It must not be taken by patients who have severe problems with their liver, or who are taking the following medicines:

• rifampicin (used to treat tuberculosis);
• ritonavir-boosted lopinavir;
• St John’s wort (a herbal preparation used to treat depression);
• medicines that are broken down in the same way as Prezista and are harmful at high levels in the blood. See the package leaflet for the full list of these medicines.

The 300- and 600-mg tablets contain a colouring agent called sunset yellow (E110), which can cause allergies. Patients who are allergic to this agent may need to take the lower strength tablets, which do not contain sunset yellow.

Why has Prezista been approved?

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

Prezista was originally given ‘conditional approval’. This means that there was more evidence to come about the medicine, in particular its safety. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full approval.

Other information about Prezista

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Prezista to Janssen-Cilag International NV on 12 February 2007. This was switched to a full marketing authorisation on 16 December 2008. The marketing authorisation is valid for five years, after which it can be renewed.

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

This EPAR was last updated on 03/05/2012 .

More detail is available in the summary of product characteristics

Product details

Publication details

Product information

12/04/2012  Prezista -EMEA/H/C/000707 -IB/0048

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

Prezista, co-administered with low dose ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of patients with human immunodeficiency virus (HIV-1) infection.

Prezista 75, 150, 300 and 600 mg tablets may be used to provide suitable dose regimens: 

• For the treatment of HIV-1 infection in antiretroviral treatment (ART) experienced adult patients, including those that have been highly pre treated.
• For the treatment of HIV-1 infection in ART experienced children and adolescents from the age of 6 years and at least 20 kg body weight.

In deciding to initiate treatment with Prezista co-administered with low dose ritonavir careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different agents. Genotypic or phenotypic testing (when available) and treatment history should guide the use of Prezista.

Prezista, co-administered with low dose ritonavir is indicated in combination with other antiretroviral medicinal products for the treatment of patients with human immunodeficiency virus (HIV-1) infection.

PREZISTA 400 mg tablets may be used to provide suitable dose regimens:

• For the treatment of HIV-1 infection in ART naïve adults.
• For the treatment of HIV-1 infection in ART-experienced adults with no darunavir resistance associated mutations (DRV-RAMs) and who have plasma HIV-1 RNA <100,000 copies/ml and CD4+ cell count ≥100 cells x 10⁶/l. In deciding to initiate treatment with Prezista in such ART-experienced adults genotypic testing should guide the use of Prezista.

Changes since initial authorisation of medicine

Initial marketing-authorisation documents