Effentora

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Questions and answers

On 11 July 2013, Teva Pharma B.V. officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a new indication for Effentora, to extend the treatment for breakthrough pain to adult patients with chronic (long-term) persistent pain from causes other than cancer.

What is Effentora?

Effentora is a medicine that contains the active substance fentanyl. It is already used to treat ‘breakthrough’ pain in adults with cancer who are using opioid painkillers to control long-term cancer pain. Breakthrough pain is when a patient experiences additional, sudden pain in spite of ongoing treatment with painkillers.

Effentora is available as ‘buccal tablets’ (tablets that dissolve in the mouth). It has been authorised in the European Union since 4 April 2008.

What was Effentora expected to be used for?

Effentora was also expected to be used to treat breakthrough pain in adults with long-term persistent pain from causes other than cancer, who were already receiving regular treatment with opioids to control their persistent pain.

How was Effentora expected to work?

In adults with long-term pain due to causes other than cancer, Effentora was expected to work in the same way as it does in adults with cancer pain.

The active substance in Effentora, fentanyl, is an opioid. It is a well-known substance, which has been used to control pain for many years. In Effentora, it is given as a buccal tablet, so that fentanyl is absorbed through the lining of the mouth. Once absorbed, fentanyl acts on receptors in the brain and spinal cord to control pain.

What did the company present to support its application?

The applicant presented data from three main studies in adults with breakthrough pain already using opioids. The effects of Effentora were compared with those of placebo (a dummy treatment) in 79 patients with neuropathic pain (pain due to nerve damage) in one study, and in 77 patients with low-back pain in a second study. The duration of treatment was determined by the time needed by each patient to control nine episodes of breakthrough pain within a 21-day period. The third study, which lasted for 12 weeks, looked at the effects of Effentora in 148 patients with non-cancer-related long-term pain. In all of the studies, the main measure of effectiveness was the change in pain intensity in the 60 minutes after taking the tablet. Each patient ranked their pain intensity on a scale of 0 to 10.

How far into the evaluation was the application when it was withdrawn?

The application was withdrawn after the CHMP had evaluated the documentation provided by the company and formulated lists of questions. After the CHMP had assessed the company’s responses to the questions, there were still some unresolved issues.

What was the recommendation of the CHMP at that time?

Based on the review of the data and the company’s response to the CHMP lists of questions, at the time of the withdrawal, the CHMP had concerns and was of the provisional opinion that Effentora could not have been approved for the treatment of breakthrough pain in adults with long-term pain other than cancer pain.

The CHMP considered that, although the use of Effentora is accepted in cancer patients who have limited survival, further data were needed to support its safe use in adults with non-cancer-related pain, who have normal life expectancy and may need long-term treatment. The Committee noted that several cases of misuse or abuse of the medicine had been reported in the studies, and was concerned about the risk of addiction in non-cancer patients when using Effentora in the long term. The Committee also had concerns that the patients in the studies had high levels of background pain and might not have been representative of the intended treatment group, which consists of patients with breakthrough pain but whose background pain is otherwise well controlled by regular opioid treatment.

Therefore, at the time of the withdrawal, the CHMP was of the opinion that the benefits of Effentora in patients with non-cancer-related long-term pain did not outweigh its risks.

What were the reasons given by the company for withdrawing the application?

In its official letter, the company stated that it decided to withdraw the application after the CHMP indicated that the data submitted were not sufficient to address the Committee’s concerns.

The withdrawal letter is available under the tab 'All documents'.

What consequences does this withdrawal have for patients in clinical trials?

The company informed the CHMP that there are no consequences for patients currently included in clinical trials with Effentora.

If you are in a clinical trial and need more information about your treatment, contact the doctor who is giving it to you.

What is happening with Effentora for the treatment ‘breakthrough’ pain in adults with cancer?

There are no consequences on the use of Effentora in its authorised indication.

Name Language First published Last updated
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) BG = bălgarski 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) ES = español 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) CS = čeština 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) DA = dansk 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) DE = Deutsch 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) ET = eesti keel 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) EL = elliniká 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) EN = English 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) FR = français 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) IT = italiano 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) LV = latviešu valoda 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) LT = lietuvių kalba 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) HU = magyar 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) MT = Malti 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) NL = Nederlands 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) PL = polski 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) PT = português 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) RO = română 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) SK = slovenčina 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) SL = slovenščina 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) FI = suomi 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) SV = svenska 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) HR = Hrvatski 26/07/2013  

News

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 July 2013

This page provides an overview of the opinions adopted at the July 2013 meeting of the Committee for Medicinal Products for Human Use (CHMP) and other important outcomes.

At its July meeting, the CHMP welcomed Ivana Mikacic as the Croatian member of the Committee following the accession of Croatia to the European Union on 1 July 2013. Ana Dugonjic has been appointed as the Croatian alternate. This addition brings the total number of CHMP members to 33.

Eight new medicines recommended for approval

The CHMP recommended the approval of Giotrif for the treatment of lung cancer.

The CHMP also recommended that Incresync, Vipdomet and Vipidia should be granted marketing authorisations for the treatment of type-2 diabetes.

Ultibro Breezhaler and Xoterna Breezhaler received positive opinions from the Committee for the treatment of chronic obstructive pulmonary disease (COPD).

The Committee recommended that Tybost should be granted a marketing authorisation for the treatment of human-immunodeficiency-virus-1 (HIV-1) infection in combination with the protease inhibitors atazanavir and darunavir.

The Committee also gave a positive recommendation for the approval of Grastofil, a biosimilar medicine for the treatment of neutropenia.

Negative opinion for Delamanid

The Committee adopted a negative opinion for Delamanid, which was intended for the treatment of multi-drug-resistant tuberculosis.

Seven recommendations on extensions of therapeutic indications

The CHMP recommended extensions to the existing indications for Eylea, Ilaris, Prezista, Revolade, Simponi, Stelara and Zonegran.

Re-examination of two initial recommendations for marketing authorisation

The CHMP adopted a positive re-examination opinion for Defitelio, for the treatment of severe hepatic veno-occlusive disease (VOD) in patients undergoing blood-stem-cell transplantation.

It also adopted a final negative opinion following the re-examination of Xeljanz which was intended for the treatment of moderate to severe active rheumatoid arthritis.

Investigation on GLP-1 based diabetes therapies concluded

The CHMP has finalised a review of glucagon-like-peptide-1 (GLP-1)-based diabetes therapies. The Committee concluded that available data do not confirm recent concerns over an increased pancreatic cancer risk with these medicines. For more information, please see the press release in the grid below.

Outcome of two further safety reviews

In addition to the safety review on GLP-1-based diabetes therapies, the Committee also issued recommendations on ketoconazole-containing medicines for oral use and metoclopramide-containing medicines.

More information on these and all other outcomes of this month’s meeting are available in the table below.

 

Positive recommendations on new medicines

Name of medicine Giotrif
International non-proprietary name (INN) afatinib
Marketing-authorisation applicant Boehringer Ingelheim International GmbH
Therapeutic indication Treatment of epidermal-growth-factor-receptor (EGFR) tyrosine-kinase-inhibitor-naïve adult patients with locally advanced or metastatic non-small-cell lung cancer with activating EGFR mutations
More information Summary of opinion for Giotrif

 

Name of medicine Grastofil
International non-proprietary name (INN) filgrastim
Marketing-authorisation applicant Apotex Europe BV
Therapeutic indication Treatment of neutropenia
More information Summary of opinion for Grastofil

 

Name of medicine Incresync
INN alogliptin / pioglitazone
Marketing-authorisation applicant Takeda Pharma A/S
Therapeutic indication Treatment of type-2 diabetes mellitus
More information Summary of opinion for Incresync

 

Name of medicine Tybost
INN cobicistat
Marketing-authorisation applicant Gilead Sciences International Ltd
Therapeutic indication Tybost is indicated as a pharmacokinetic enhancer of atazanavir 300 mg once daily or darunavir 800 mg once daily as part of antiretroviral combination therapy in HIV-1-infected adults
More information Summary of opinion for Tybost

 

Name of medicine Ultibro Breezhaler
INN glycopyrronium bromide / indacaterol
Marketing-authorisation applicant Novartis Europharm Ltd
Therapeutic indication Treatment of COPD
More information Summary of opinion for Ultibro Breezhaler

 

Name of medicine Vipdomet
INN alogliptin / metformin
Marketing-authorisation applicant Takeda Pharma A/S
Therapeutic indication Treatment of type-2 diabetes mellitus
More information Summary of opinion for Vipdomet

 

Name of medicine Vipidia
INN alogliptin
Marketing-authorisation applicant Takeda Pharma A/S
Therapeutic indication Treatment of type-2 diabetes mellitus
More information Summary of opinion for Vipidia

 

Name of medicine Xoterna Breezhaler
INN glycopyrronium bromide / indacaterol
Marketing-authorisation applicant Novartis Europharm Ltd
Therapeutic indication Treatment of COPD
More information Summary of opinion for Xoterna Breezhaler

    

Negative recommendation on new medicine

Name of medicine Delamanid
INN delamanid
Marketing-authorisation applicant Otsuka Novel Products GmbH
Therapeutic indication Treatment of multi-drug-resistant tuberculosis
More information Questions and answers on the refusal of the marketing authorisation for Delamanid

 

Re-examinations of initial recommendations for marketing authorisation

Name of medicine Defitelio
INN defibrotide
Marketing-authorisation applicant Gentium S.p.A.
Therapeutic indication Treatment of severe VOD in patients undergoing blood-stem-cell transplantation
More information

Summary of opinion for Defitelio


Questions and answers on the positive opinion on the marketing authorisation for Defitelio

  

Name of medicine Xeljanz
INN tofacitinib
Marketing-authorisation applicant Pfizer Limited
Therapeutic indication Treatment of moderate to severe active rheumatoid arthritis
More information Questions and answers on the refusal of the marketing authorisation for Xeljanz

 

Positive recommendations on extensions of therapeutic indications  

Name of medicine Eylea
INN aflibercept
Marketing-authorisation holder Bayer Pharma AG
Change to the indication
(changes in bold)
Eylea is indicated for adults for the treatment of:
- neovascular (wet) age-related macular degeneration (see section 5.1);
- visual impairment due to macular oedema secondary to central-retinal-vein occlusion (see section 5.1).
More information Summary of opinion for Eylea

 

Name of medicine Ilaris
INN canakinumab
Marketing-authorisation holder Novartis Europharm Ltd.
Change to the indication
(changes in bold)
 
Ilaris is indicated for the treatment of cryopyrin-associated periodic syndromes in adults, adolescents and children aged two years and older with body weight of 7.5 kg or above, including:
- Muckle-Wells syndrome (MWS);
- neonatal-onset multisystem inflammatory disease / chronic infantile neurological, cutaneous, articular syndrome;
- severe forms of familial cold auto-inflammatory syndrome / familial cold urticaria presenting with signs and symptoms beyond cold-induced urticarial skin rash
- Ilaris is indicated for the treatment of active systemic juvenile idiopathic arthritis in patients aged two years and older who have responded inadequately to previous therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids. Ilaris can be given as monotherapy or in combination with methotrexate.
More information Summary of opinion for Ilaris

  

Name of medicine Prezista
INN darunavir
Marketing-authorisation holder Janssen-Cilag International N.V.
Change to the indication
(changes in bold)
Prezista 400- and 800-mg tablets may be used to provide suitable dose regimens for the treatment of HIV-1 infection in adult and paediatric patients from the age of 12 years and at least 40 kg body weight who are:
-
antiretroviral-therapy (ART)-naïve (see section 4.2);
- ART-experienced with no darunavir-resistance-associated mutations 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 patients, genotypic testing should guide the use of Prezista (see sections 4.2, 4.3, 4.4 and 5.1).
More information Summary of opinion for Prezista

 

Name of medicine Revolade
INN eltrombopag
Marketing-authorisation holder GlaxoSmithKline Trading Services
Change to the indication
(changes in bold)
- Revolade is indicated for adult chronic-immune (idiopathic)-thrombocytopenic-purpura splenectomised patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). Revolade may be considered as second-line treatment for adult non-splenectomised patients where surgery is contraindicated.
- Revolade is indicated in adult patients with chronic hepatitis-C-virus infection for the treatment of thrombocytopenia, where the degree of thrombocytopenia is the main factor preventing the initiation or limiting the ability to maintain optimal interferon-based therapy.
More information Summary of opinion for Revolade

 

Name of medicine Simponi
INN golimumab
Marketing-authorisation holder Janssen Biologics B.V.
Change to the indication
(changes in bold)

Rheumatoid arthritis (RA)

Simponi, in combination with methotrexate (MTX), is indicated for:
- the treatment of moderate to severe, active RA in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate;
- the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX.

Simponi, in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function.

Psoriatic arthritis (PsA)

Simponi, alone or in combination with MTX, is indicated for the treatment of active and progressive PsA in adult patients when the response to previous DMARD therapy has been inadequate. Simponi has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease (see section 5.1) and to improve physical function.

Ankylosing spondylitis (AS)

Simponi is indicated for the treatment of severe, active AS in adults who have responded inadequately to conventional therapy.

Ulcerative colitis (UC)

Simponi is indicated for treatment of moderately to severely active UC in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6‑mercaptopurine or azathioprine, or who are intolerant to or have medical contraindications for such therapies.

More information Summary of opinion for Simponi

 

Name of medicine Stelara
INN ustekinumab
Marketing-authorisation holder Janssen-Cilag International N.V.
Change to the indication
(changes in bold)

Plaque psoriasis

Stelara is indicated for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, MTX and psoralen ultraviolet A (see section 5.1).

PsA

Stelara, alone or in combination with MTX, is indicated for the treatment of active PsA in adult patients when the response to previous non-biological DMARD therapy has been inadequate (see section 5.1).

More information Summary of opinion for Stelara

 

Name of medicine Zonegran
INN zonisamide
Marketing-authorisation holder Eisai Ltd
Extension of indication
(changes in bold)
Zonegran is indicated as:
- monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy;
- adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents and children aged six years and above.
More information Summary of opinion for Zonegran

 

Recommendation on other variations

Name of medicine Insuman
INN insulin human
Marketing-authorisation holder Sanofi-aventis Deutschland GmbH
More information Summary of opinion for Insuman

 

Withdrawal of applications

Name of medicine Effentora
INN fentanyl citrate
More information Effentora: Withdrawn application

 

Name of medicine Eviplera
INN emtricitabine / rilpivirine hydrochloride / tenofovir disoproxil fumarate
More information Eviplera: Withdrawn application

  

Outcome of arbitration procedure

Name of medicine Methylphenidate Hexal
INN methylphenidate hydrochloride  
Marketing-authorisation holder Hexal A/S
More information Methylphenidate Hexal: Article-29 referral

 

Name of medicine Methylphenidate Sandoz
INN methylphenidate hydrochloride  
Marketing-authorisation holder Sandoz A/S
More information Methylphenidate Sandoz: Article-29 referral

 

Opinion on any scientific matter (Article 5(3))

Name of medicine GLP-1 based therapies
INN exenatide, liraglutide, lixisenatide, sitagliptin, saxagliptin, vildagliptin, linagliptin
More information Investigation into GLP-1-based diabetes therapies concluded

 

Public-health communications on non-centrally authorised medicines

Name of medicine Ketoconazole-containing medicines for oral use
INN ketoconazole
More information Ketoconazole-containing medicines: Article-31 referral

 

European Medicines Agency recommends suspension of marketing authorisations for oral ketoconazole

 

Name of medicine Metoclopramide-containing medicines
INN metoclopramide
More information Metoclopramide-containing medicines: Article-31 referral

 

European Medicines Agency recommends changes to the use of metoclopramide

 

Other updates

Opinions on annual re-assessments, renewals of marketing authorisations and accelerated assessment procedures
Opinions on safety variations
Start of Community reviews
Scientific advice and protocol assistance
Guidelines and concept papers adopted
Overview of invented names reviewed in July 2013 by the Name Review Group (NRG)
Organisational matters
Opinions on consultation procedures on ancillary medicinal substances in medical devices

 

Key facts

Product details for Effentora
NameEffentora
Product numberEMEA/H/C/000833
Date of issue of marketing authorisation valid throughout the European Union (if applicable)04/04/2008
International non-proprietary name or common name

fentanyl

Active substancefentanyl
Date of withdrawal11/07/2013
Company making the application

Teva B.V.

Withdrawal typePost-authorisation

All documents

Name Language First published Last updated
Withdrawal assessment report for Effentora (English only) 29/08/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) BG = bălgarski 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) ES = español 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) CS = čeština 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) DA = dansk 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) DE = Deutsch 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) ET = eesti keel 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) EL = elliniká 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) EN = English 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) FR = français 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) IT = italiano 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) LV = latviešu valoda 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) LT = lietuvių kalba 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) HU = magyar 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) MT = Malti 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) NL = Nederlands 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) PL = polski 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) PT = português 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) RO = română 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) SK = slovenčina 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) SL = slovenščina 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) FI = suomi 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) SV = svenska 26/07/2013  
Questions and answers on the withdrawal of the application for a change to the marketing authorisation for Effentora (fentanyl) HR = Hrvatski 26/07/2013  
Withdrawal letter: Effentora (English only) 26/07/2013  

Related information

Related information on withdrawals

The question-and-answer (Q&A) document provides a summary of the CHMP's evaluation of the application at the time of the withdrawal, and includes a link to the company's formal withdrawal letter.

An assessment report is published when the application is withdrawn after the first stage of the CHMP's evaluation is completed ('day 90').