Ceplene

histamine dihydrochloride

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

What is Ceplene?

Ceplene is a solution for injection that contains the active substance histamine dihydrochloride (0.5 mg/0.5 ml).

What is Ceplene used for?

Ceplene is used in combination with interleukin-2 (an anticancer medicine) as maintenance treatment in adults with acute myeloid leukaemia (AML), a type of cancer affecting the white blood cells. It is used during the patients’ first ‘remission’ (a period without symptoms of the disease after the first course of treatment). The effectiveness of Ceplene has not been fully demonstrated in patients older than 60 years of age.

Because the number of people with AML is low, the disease is rare, and Ceplene was designated as an ‘orphan medicine’ (a medicine used in rare disease) on 11 April 2005.

The medicine can only be obtained with a prescription.

How is Ceplene used?

Ceplene should be given under the supervision of a doctor who has experience in the treatment of AML. The recommended dose of Ceplene is a 0.5-mg injection under the skin, twice a day, one to three minutes after an interleukin-2 injection. Ceplene and interleukin-2 are given for 10 cycles.

For the first three cycles, each cycle consists of three weeks of treatment, followed by a three-week rest period. For the following seven cycles, each cycle consists of three weeks of treatment, followed by a six-week rest period.

When Ceplene is first given, the patient’s blood pressure, heart rate and lung function must be monitored. Depending on the patient’s response to treatment and side effects, the treatment may have to be suspended or the dose adjusted.

Each Ceplene injection must be given slowly over five to 15 minutes, in a different site from the interleukin-2 injection, and preferably in the thigh or abdomen (tummy). Patients can inject themselves once they have been trained appropriately.

How does Ceplene work?

The active substance in Ceplene, histamine dihydrochloride, is an immune modulator. This means that it alters the activity of the immune system (the body’s natural defences). Histamine is a naturally occurring substance in the body that is involved in many processes. In the treatment of AML, it is thought to work by protecting immune system cells from damage. This improves the effectiveness of interleukin-2, a medicine that stimulates the immune system to attack cancerous cells. When Ceplene is given with interleukin-2, it helps the immune system to kill the leukaemia cells that may remain in the body during remission. This can increase the length of time the patient stays in remission.

How has Ceplene been studied?

The effectiveness of Ceplene has been studied in one main study involving 320 adults with AML who were in remission following leukaemia treatment. Ceplene was given in combination with interleukin-2 and compared with no treatment. The main measure of effectiveness was the length of time until the disease came back or the patient died.

What benefit has Ceplene shown during the studies?

The combination of Ceplene and interleukin-2 was more effective than no treatment in increasing the time until AML came back or the patient died: in the patients in their first complete remission, the average time without disease increased from 291 days with no treatment to 450 days after treatment with Ceplene and interleukin-2. No effect of Ceplene and interleukin-2 was seen in patients in second or later remission.

What is the risk associated with Ceplene?

The most common side effects with Ceplene (seen in more than 1 patient in 10) are upper respiratory tract infection (colds), eosinophilia (an increase in eosinophil levels, a type of white blood cell), thrombocytopenia (low blood platelet counts), headache, dizziness, dysgeusia (a bitter or unusual taste in the mouth), tachycardia (rapid heart beat), flushing (reddening), hypotension (low blood pressure), cough, dyspnoea (shortness of breath), nausea (feeling sick), dyspepsia (indigestion), diarrhoea, rash, arthralgia (pain in the joints), myalgia (muscle pain), pyrexia (fever), chills, fatigue (tiredness), flu-like symptoms, feeling hot and injection site reactions (redness, itching, pain and inflammation). For the full list of all side effects reported with Ceplene, see the package leaflet.

Ceplene must not be used in patients who have severe heart problems or in women who are pregnant or breast-feeding. It must also not be used in patients who have received a bone marrow transplant from a donor, or who are taking steroids (medicines used to reduce or prevent inflammation) given systemically (given as treatment throughout the body), clonidine (used to reduce high blood pressure) or histamine H2 blockers (used to treat stomach ulcers, indigestion or heartburn). For the full list of restrictions, see the package leaflet.

Why has Ceplene been approved?

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

Ceplene has been authorised under ‘exceptional circumstances’. This means that because the disease is rare, it has not been possible to obtain complete information about Ceplene. 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 Ceplene?

The company will carry out further studies to look in more detail at the effectiveness of the combination of Ceplene and interleukin-2 and at how the combination works.

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

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

Other information about Ceplene

The European Commission granted a marketing authorisation valid throughout the European Union for Ceplene on 7 October 2008.

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

Name Language First published Last updated
Ceplene : EPAR - Summary for the public BG = bălgarski 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public ES = español 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public CS = čeština 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public DA = dansk 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public DE = Deutsch 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public ET = eesti keel 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public EL = elliniká 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public EN = English 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public FR = français 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public IT = italiano 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public LV = latviešu valoda 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public LT = lietuvių kalba 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public HU = magyar 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public MT = Malti 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public NL = Nederlands 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public PL = polski 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public PT = português 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public RO = română 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public SK = slovenčina 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public SL = slovenščina 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public FI = suomi 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public SV = svenska 11/11/2008 10/04/2014
Ceplene : EPAR - Summary for the public HR = Hrvatski 11/11/2008 10/04/2014

This EPAR was last updated on 10/04/2014 .

Authorisation details

Product details

Product details for Ceplene
NameCeplene
Agency product numberEMEA/H/C/000796
Active substance

histamine dihydrochloride

International non-proprietary name (INN) or common name

histamine dihydrochloride

Therapeutic area Leukemia, Myeloid, Acute
Anatomical therapeutic chemical (ATC) code L03AX14
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 Ceplene
Marketing-authorisation holder

Meda AB

Revision8
Date of issue of marketing authorisation valid throughout the European Union07/10/2008

Contact address:

Meda AB
Pipers väg 2A
SE-170 09 Solna
Sweden
 

Product information

Product information

21/03/2014  Ceplene -EMEA/H/C/000796 -S/0014

Name Language First published Last updated
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014
Ceplene : EPAR - Product Information HR = Hrvatski 28/10/2008 10/04/2014

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
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  
Ceplene : EPAR - All Authorised presentations HR = Hrvatski 28/10/2008  

Pharmacotherapeutic group

Immunostimulants

Therapeutic indication

Ceplene maintainance therapy is indicated for adult patients with acute myeloid leukaemia in first remission concomitantly treated with interleukin-2 (IL-2). The efficacy of Ceplene has not been fully demonstrated in patients older than age 60.

Assessment History

Changes since initial authorisation of medicine

Name Language First published Last updated
Ceplene : EPAR - Procedural steps taken and scientific information after authorisation HR = Hrvatski 17/05/2010 10/04/2014
Ceplene-H-C-796-A20-11 : EPAR - Assessment Report - Article 20 HR = Hrvatski 23/08/2012  

Initial marketing-authorisation documents