Defitelio

defibrotide

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

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

What is Defitelio and what is it used for?

Defitelio is a medicine containing the active substance defibrotide. It is used to treat severe veno-occlusive disease (VOD) in patients undergoing haematopoietic (blood) stem-cell transplantation. VOD is a condition in which the veins in the liver become blocked, leading to liver dysfunction. Defitelio is used in adults and in children from one month of age.

Because the number of patients with VOD is low, the disease is considered ‘rare’, and Defitelio was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 29 July 2004.

How is Defitelio used?

Defitelio can only be obtained with a prescription and must be prescribed and given by a doctor experienced in the management of complications of haematopoietic stem cell transplantation. It is available as a concentrate to be made into a solution for infusion (drip) into a vein. Defitelio is given four times a day at a dose of 6.25 mg per kg body-weight. Treatment should last for at least for 3 weeks and continue until the patient’s symptoms resolve.

How does Defitelio work?

VOD is usually a complication resulting from a treatment, known as ‘myeloablative chemotherapy’, that is given to patients before blood stem-cell transplantation. Myeloablative chemotherapy is used to clear the patient’s bone marrow of cells before receiving healthy stem cells from a donor. The medicines used for this treatment can damage the lining of the blood vessels in the liver, leading to the formation of clots and obstruction of the vessels seen in VOD.

The active substance in Defitelio, defibrotide, works by increasing the breakdown of clots in the blood. In addition, there is experimental evidence that Defibrotide may protect the cells lining blood vessels.

What benefits of Defitelio have been shown in studies?

Severe VOD is known to have a high mortality rate, ranging between 75 and 85% and in some patient registries exceeding 85%. In one main study involving 102 patients with severe VOD following blood stem-cell transplantation, Defitelio was compared with a historical control group of patients who had received standard supportive care. Defitelio was shown to lower the mortality rate to 62% at 100days after transplantation, and in 24% of patients the symptoms of severe VOD were completely resolved after 100days.

Benefits of Defitelio were also seen in data from a patient registry in the United States, where patients with severe VOD following blood stem-cell transplantation who received Defitelio plus standard care had better outcomes than those given standard care alone, including a higher 100-day survival rate (39% versus 31%) and a higher proportion of patients whose VOD resolved (51% versus 29%).

What are the risks associated with Defitelio?

The most common side effects with Defitelio (which may affect up to 1 in 10 people) are bleeding, hypotension (low blood pressure) and coagulopathy (problems with blood clotting). For the full list of all side effects reported with Defitelio, see the package leaflet.

Defitelio must also not be used together with other medicines that break down blood clots. For the full list of restrictions, see the package leaflet.

Why is Defitelio approved?

The Agency’s Committee for Medicinal Products for Human Use (CHMP) concluded that Defitelio’s benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP considered that Defitelio had been shown to improve survival in patients with severe VOD. Although it was not possible to conduct a study directly comparing Defitelio with placebo (dummy treatment), the company had provided sufficient data to show that patients treated with the medicine had improved chances of survival. The side effects seen, such as bleeding, were considered manageable and it was not possible to determine with certainty whether they were caused by Defitelio.

Defitelio has been authorised under ‘exceptional circumstances’. This is because it has not been possible to obtain complete information about Defitelio due to the rarity of the disease. Every year, the European Medicines Agency will review any new information that becomes available and this summary will be updated as necessary.

What information is still awaited for Defitelio?

Since Defitelio has been approved under exceptional circumstances, the company that markets the medicine is required to set up a patient registry to provide further data on long-term safety, health outcomes, and the way the medicine is used in practice. The company will ensure that all healthcare professionals who are expected to use the medicine are provided with information on how to enter their patients in the registry.

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

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

Other information about Defitelio

The European Commission granted a marketing authorisation valid throughout the European Union for Defitelio on 18 October 2013.

Name Language First published Last updated
Defitelio : EPAR - Summary for the public BG = bălgarski 25/10/2013  
Defitelio : EPAR - Summary for the public ES = español 25/10/2013  
Defitelio : EPAR - Summary for the public CS = čeština 25/10/2013  
Defitelio : EPAR - Summary for the public DA = dansk 25/10/2013  
Defitelio : EPAR - Summary for the public DE = Deutsch 25/10/2013  
Defitelio : EPAR - Summary for the public ET = eesti keel 25/10/2013  
Defitelio : EPAR - Summary for the public EL = elliniká 25/10/2013  
Defitelio : EPAR - Summary for the public EN = English 25/10/2013  
Defitelio : EPAR - Summary for the public FR = français 25/10/2013  
Defitelio : EPAR - Summary for the public IT = italiano 25/10/2013  
Defitelio : EPAR - Summary for the public LV = latviešu valoda 25/10/2013  
Defitelio : EPAR - Summary for the public LT = lietuvių kalba 25/10/2013  
Defitelio : EPAR - Summary for the public HU = magyar 25/10/2013  
Defitelio : EPAR - Summary for the public MT = Malti 25/10/2013  
Defitelio : EPAR - Summary for the public NL = Nederlands 25/10/2013  
Defitelio : EPAR - Summary for the public PL = polski 25/10/2013  
Defitelio : EPAR - Summary for the public PT = português 25/10/2013  
Defitelio : EPAR - Summary for the public RO = română 25/10/2013  
Defitelio : EPAR - Summary for the public SK = slovenčina 25/10/2013  
Defitelio : EPAR - Summary for the public SL = slovenščina 25/10/2013  
Defitelio : EPAR - Summary for the public FI = suomi 25/10/2013  
Defitelio : EPAR - Summary for the public SV = svenska 25/10/2013  
Defitelio : EPAR - Summary for the public HR = Hrvatski 25/10/2013  

This EPAR was last updated on 25/09/2014 .

Authorisation details

Product details

Product details for Defitelio
NameDefitelio
Agency product numberEMEA/H/C/002393
Active substance

defibrotide

International non-proprietary name (INN) or common name

defibrotide

Therapeutic area Hepatic Veno-Occlusive Disease
Anatomical therapeutic chemical (ATC) code B01AX01
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.

Exceptional Circumstances

There were "exceptional circumstances" concerning the approval of this medicine. This happens when the applicant can show that they are unable to provide comprehensive data on the efficacy and safety of the medicine for which authorisation is being sought, due to the rarity of the condition it is intended for, limited scientific knowledge in the area concerned, or ethical considerations involved in the collection of such data.

Publication details

Publication details for Defitelio
Marketing-authorisation holder

Gentium SpA

Revision1
Date of issue of marketing authorisation valid throughout the European Union18/10/2013

Contact address:

Gentium SpA
Piazza XX Settembre 2
22079 Villa Guardia (Como)
Italy

Product information

Product information

20/02/2014  Defitelio -EMEA/H/C/002393 -II/0001

Name Language First published Last updated
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014
Defitelio : EPAR - Product Information HR = Hrvatski 25/10/2013 25/09/2014

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
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  
Defitelio : EPAR - All Authorised presentations HR = Hrvatski 25/10/2013  

Pharmacotherapeutic group

Antithrombotic agents

Therapeutic indication

Defitelio is indicated for the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstructive syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy.

It is indicated in adults and in adolescents, children and infants over 1 month of age.

Assessment History

Changes since initial authorisation of medicine

Name Language First published Last updated
Defitelio : EPAR - Procedural steps taken and scientific information after authorisation HR = Hrvatski 25/09/2014  

Initial marketing-authorisation documents

Authorised

This medicine is approved for use in the European Union

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