Votubia

everolimus

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

What is Votubia?

Votubia is a medicine that contains the active substance everolimus. It is available as tablets (2.5, 5 and 10 mg) and as dispersible tablets (2, 3 and 5 mg).

What is Votubia used for?

Votubia is used to treat the following benign (non-cancerous) tumours caused by the genetic disease tuberous sclerosis:

  • subependymal giant cell astrocytoma (SEGA), a benign tumour of the brain, where it is used in adults and children whose brain tumour cannot be surgically removed;
  • renal angiomyolipoma, a benign tumour of the kidneys, where it is used in adults who are at risk of complications but who do not require immediate surgery. 

Because the number of patients with tuberous sclerosis is low, the disease is considered ‘rare’, and Votubia was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 4 August 2010. 

The medicine can only be obtained with a prescription.

How is Votubia used?

Votubia treatment should be started by a doctor experienced in treating tuberous sclerosis and in drug monitoring.

Votubia is taken by mouth once a day at the same time every day, consistently either with or without food.

For SEGA, the starting dose depends on the body surface area (calculated using the patient’s height and weight), but the doctor will adjust the dose based on the patient’s blood levels of the medicine and how well the patient tolerates the medicine.

In patients with renal angiomyolipoma, the recommended dose is 10 mg once a day. In case patients experience severe side effects, the doctor may need to reduce the dose or interrupt treatment temporarily.

Patients with mild or moderate impairment of liver function should be started at a lower dose. Votubia is not recommended for patients with SEGA and severe impairment of liver function. For patients with renal angiomyolipoma and severe impairment of liver function, Votubia is only recommended if the desired benefit outweighs the risk.

How does Votubia work?

The active substance in Votubia, everolimus, is an antitumour medicine that acts by blocking an enzyme called ‘mammalian target of rapamycin’ (mTOR), which has increased activity in tumour cells of patients with SEGA or renal angiomyolipoma. In the body, everolimus first attaches to a protein called FKBP-12 that is found inside cells to make a ‘complex’. This complex then blocks mTOR. Since mTOR is involved in the control of cell division and the growth of blood vessels, Votubia prevents the division of tumour cells and reduces their blood supply.

How has Votubia been studied?

In SEGA caused by tuberous sclerosis, Votubia has been studied in two main studies: the first study involved 28 adults and children aged three years and above. The main measure of effectiveness was based on how much the patient’s main brain tumour shrank after six months of treatment. The second study involved 117 patients (including 20 children aged below 3 years) and compared Votubia with placebo (a dummy treatment). The main measure of effectiveness was the proportion of patients who responded to treatment and whose brain tumour shrank by at least half after six months of treatment.

In renal angiomyolipoma caused by tuberous sclerosis, Votubia has been compared with placebo in one study involving 118 adults. The main measure of effectiveness was the proportion of patients who responded to treatment and whose kidney tumour shrank by at least half.

What benefit has Votubia shown during the studies?

Votubia was shown to be effective at treating patients with SEGA and renal angiomyolipoma by shrinking the volume of the tumours.

In the first study in patients with SEGA, the main brain tumour shrank by half in approximately 30% of patients and by about a third in around 70% of patients. In the second study, the brain tumour shrank by at least half in 35% of patients (27 out of 78 patients) treated with Votubia, compared with none of the 39 patients who received placebo.

In patients with renal angiomyolipoma, the kidney tumour shrank by at least half in 42% of patients (33 out of 79 patients) treated with Votubia, compared with none of the 39 patients who received placebo.

What is the risk associated with Votubia?

The most common side effects (seen in more than 1 in 10 patients) in studies with Votubia are infections, stomatitis (inflammation of the lining of the mouth) and increased blood levels of cholesterol. For the full list of all side effects reported with Votubia, see the package leaflet.

Votubia must not be used in people who are hypersensitive (allergic) to everolimus, to related medicines such as sirolimus and temsirolimus or to any of the other ingredients.

Why has Votubia been approved?

The CHMP noted that Votubia has been shown to reduce the size of the brain tumours in adults and children and that this is expected to reduce the signs and symptoms of SEGA such as seizures, hydrocephalus (accumulation of fluid in the brain), and increased pressure within the brain. Although surgery remains the standard treatment for this condition, Votubia is expected to benefit patients whose tumour cannot be operated on. Votubia has also been shown to reduce the size of kidney tumours in patients with renal angiomyolipoma. The side effects of the medicine were considered to be manageable and were generally mild or moderate. The CHMP therefore concluded that the benefits of Votubia outweigh its risks and recommended that it be given marketing authorisation.

Votubia has been given ‘conditional approval’. This means that there is more evidence to come about the medicine, in particular its long-term effects. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

What information is still awaited for Votubia?

Since Votubia has been granted a conditional approval, the company that makes Votubia will provide more study results on the long-term effects of the medicine, the duration of the response to treatment and how the medicine is handled in the body.

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

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

Other information about Votubia

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Votubia on 02 September 2011.

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

Name Language First published Last updated
Votubia : EPAR - Summary for the public BG = bălgarski 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public ES = español 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public CS = čeština 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public DA = dansk 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public DE = Deutsch 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public ET = eesti keel 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public EL = elliniká 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public EN = English 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public FR = français 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public IT = italiano 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public LV = latviešu valoda 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public LT = lietuvių kalba 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public HU = magyar 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public MT = Malti 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public NL = Nederlands 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public PL = polski 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public PT = português 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public RO = română 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public SK = slovenčina 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public SL = slovenščina 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public FI = suomi 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public SV = svenska 19/09/2011 23/01/2014
Votubia : EPAR - Summary for the public HR = Hrvatski 19/09/2011 23/01/2014

This EPAR was last updated on 23/01/2014 .

Authorisation details

Product details

Product details for Votubia
NameVotubia
Agency product numberEMEA/H/C/002311
Active substance

everolimus

International non-proprietary name (INN) or common name

everolimus

Therapeutic area Astrocytoma
Anatomical therapeutic chemical (ATC) code L01XE10
Additional monitoring

This medicine is under additional monitoring. This means that it is being monitored even more intensively than other medicines. For more information, see medicines under additional monitoring.

Treatment of rare diseases

This medicine has an "orphan designation" which means that it is used to treat life-threatening or chronically debilitating conditions that affect no more than five in 10,000 people in the European Union, or are medicines which, for economic reasons, would be unlikely to be developed without incentives.

Conditional Approval

Sometimes, the CHMP recommends that a medicine be given ‘conditional approval’. This happens when the Committee has based its positive opinion on data which, while not yet comprehensive, indicate that the medicine’s benefits outweigh its risks.

The company is given obligations to fulfil, such as the performance of further studies. The approval is renewed on a yearly basis until all obligations have been fulfilled, and is then converted from a conditional approval into a normal approval. Conditional approvals can only be granted for medicines that satisfy an ‘unmet medical need’, meaning the medicine is intended to be used for a disease or condition for which no treatment is readily available, and it is therefore important that patients have early access to the medicine concerned.

Publication details

Publication details for Votubia
Marketing-authorisation holder

Novartis Europharm Ltd.

Revision7
Date of issue of marketing authorisation valid throughout the European Union02/09/2011

Contact address:

Novartis Europharm Ltd.
Wimblehurst Road
Horsham
West Sussex
RH12 5AB
United Kingdom

Product information

Product information

21/11/2013  Votubia -EMEA/H/C/002311 -II/0019

Name Language First published Last updated
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - Product Information HR = Hrvatski 19/09/2011 23/01/2014

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.


Name Language First published Last updated
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014
Votubia : EPAR - All Authorised presentations HR = Hrvatski 19/09/2011 23/01/2014

Pharmacotherapeutic group

Antineoplastic agents

Therapeutic indication

Renal angiomyolipoma associated with tuberous sclerosis complex (TSC)

Votubia is indicated for the treatment of adult patients with renal angiomyolipoma associated with tuberous sclerosis complex (TSC) who are at risk of complications (based on factors such as tumour size or presence of aneurysm, or presence of multiple or bilateral tumours) but who do not require immediate surgery. 

The evidence is based on analysis of change in sum of angiomyolipoma volume. 

Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC)

Votubia is indicated for the treatment of patients with subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC) who require therapeutic intervention but are not amenable to surgery.

The evidence is based on analysis of change in SEGA volume. Further clinical benefit, such as improvement in disease‑related symptoms, has not been demonstrated.

Assessment History

Changes since initial authorisation of medicine

Initial marketing-authorisation documents

Name Language First published Last updated
Votubia : EPAR - Public assessment report HR = Hrvatski 19/09/2011  
CHMP summary of positive opinion for Votubia HR = Hrvatski 24/06/2011