Fenspiride containing medicinal products - referral

Current status

CMDh final position

Overview

Withdrawal of marketing authorisations for fenspiride medicines

On 16 May 2019, EMA’s safety committee (PRAC) recommended that the marketing authorisations for fenspiride medicines be revoked, so the medicines can no longer be marketed in the EU. This follows a review that confirmed that these cough medicines could cause heart rhythm problems.

The PRAC considered all the available evidence in its review. This included cases of QT prolongation and torsades de pointes (abnormalities of the heart’s electrical activity that may lead to heart rhythm disturbances) in patients using these medicines, results of laboratory studies, data from published literature and stakeholder input.

Heart rhythm problems can be serious and occur suddenly, and it is not feasible to identify in advance the patients who may be at risk of these problems with fenspiride. In contrast, fenspiride medicines are used to treat non-serious cough. Therefore, the PRAC considered that these medicines should no longer be marketed.

The PRAC recommendation was adopted by the CMDh* by consensus and will be implemented directly at national level.

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*Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human

Information for patients

• Cough medicines containing fenspiride will no longer be marketed in the EU because of data showing a risk of sudden, serious heart rhythm problems.
• You should stop taking these medicines and contact your doctor or pharmacist for advice on alternative treatments, if needed. You can check the ingredients of your medicine in the package leaflet accompanying the medicine.
• Patients are only at risk of heart rhythm problems with fenspiride while they are taking these medicines.
• If you have any concerns about your medicine, discuss them with your doctor or pharmacist.
• Return unused medicines to your pharmacy for appropriate disposal.

Information for healthcare professionals

• Healthcare professionals should no longer prescribe fenspiride medicines and should advise their patients to stop taking fenspiride medicines.
• The withdrawal of the marketing authorisations of fenspiride medicines is based on case reports and nonclinical studies (including hERG channel binding) that showed that fenspiride can cause QT prolongation and has proarrhythmia potential (could cause triggering or worsening of arrhythmia) with the associated risk of torsades de pointes.
• Given the authorised uses of fenspiride for symptomatic treatment only and the seriousness of the safety concern, the benefit-risk balance of these medicines is negative for the currently authorised uses.

More about the medicines

Fenspiride medicines are available as syrup or tablets and used in adults and children from the age of 2 years to relieve cough resulting from lung diseases. In the EU, fenspiride medicines have been authorised via national procedures in Bulgaria, France, Latvia, Lithuania, Poland, Portugal and Romania and are available under various brand names (Elofen, Epistat, Eurefin, Eurespal, Fenspogal, Fosidal, Kudorp, Pneumorel, Pulneo, ???????? and ??????).

More about the procedure

The review of fenspiride was initiated on 14 February 2019 at the request of France, under Article 107i of Directive 2001/83/EC. At that time, the Pharmacovigilance Risk Assessment Committee (PRAC) recommended that supply of fenspiride medicines be suspended as a precautionary measure while the review was ongoing.

The review was first carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which made a set of recommendations.

The PRAC recommendation was sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which adopted it by consensus on 29 May 2019. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonised safety standards for medicines authorised via national procedures.

The PRAC recommendation will now be implemented by EU Member States, Iceland, Lichtenstein and Norway.

Fenspiride containing medicinal products Article-107i referral - Withdrawal of marketing authorisations for fenspiride medicines

Reference Number: EMA/285298/2019

Key facts

About this medicine

• Approved name:
  Fenspiride containing medicinal products
• International non-proprietary name (INN) or common name:
  fenspiride
• Class:
  Drugs for obstructive airway diseases

About this procedure

• Current status:
  CMDh final position
• Reference number:
  EMEA/H/A-107i/1480
• Type:
  Article 107i procedures

  This type of procedure is triggered when a Member State or the European Commission consider that urgent action is necessary because of a safety issue. Situations that fall under this procedure include consideration for suspension or revocation of the marketing authorisation for a medicine, the prohibition of supply of a medicine or major changes to the marketing authorisation such as deletion of indications, reduction of the recommended dose or new contraindications. The procedure is also applicable in case of a safety issue with a class of medicines.

• Authorisation model:
  Nationally authorised product(s)
• Decision making model:
  PRAC-CMDh

Key dates and outcomes

• Procedure start date:
  14/02/2019
• PRAC recommendation date:
  17/05/2019
• CHMP opinion date:
  29/05/2019

All documents

Procedure started

Fenspiride containing medicinal products Article-107i referral - Suspension of fenspiride medicines due to potential risk of heart rhythm problems

Reference Number: EMA/114407/2019

Fenspiride containing medicinal products Article-107i referral - Stakeholders submission form

Fenspiride containing medicinal products Article-107i referral - Notification

Fenspiride containing medicinal products Article-107i referral - PRAC List of questions to be addressed by the stakeholders

Reference Number: EMA/PRAC/100386/2019

Fenspiride containing medicinal products Article-107i referral - Rationale for triggering

Fenspiride containing medicinal products Article-107i referral - Annex I

DraftReference Number: EMA/121740/2019 Rev.1

Fenspiride containing medicinal products Article-107i referral - PRAC list of questions

Reference Number: EMA/PRAC/100387/2019

Fenspiride containing medicinal products Article-107i referral - Timetable for the procedure

Reference Number: EMA/PRAC/100392/2019

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Fenspiride containing medicinal products Article-107i referral - Withdrawal of marketing authorisations for fenspiride medicines

Reference Number: EMA/264639/2019

Position provided by CMDh

Fenspiride containing medicinal products Article-107i referral - Annex I

Fenspiride containing medicinal products Article-107i referral - Annex II

Fenspiride containing medicinal products Article-107i referral - Assessment report

AdoptedReference Number: EMA/317731/2019

Fenspiride containing medicinal products Article-107i referral - Annex III

Fenspiride containing medicinal products Article-107i referral - Withdrawal of marketing authorisations for fenspiride medicines

Reference Number: EMA/285298/2019

Description of documents published

Please note that some of the listed documents apply only to certain procedures.

• Overview - lay-language summary of the stage of the procedure
• Notification – a letter from a Member State, the European Commission or the marketing authorisation holder requesting the initiation of the procedure
• Scientific background – further background information from the triggering Member State on the issues leading to the initiation of the procedure (if applicable)
• List of questions – questions agreed by the Committee requesting further information from the marketing authorisation holder(s) / applicant(s) to evaluate the issues identified
• Timetable for the procedure – agreed timeframe to respond to the list of questions, to assess the issues and to adopt a conclusion
• List of medicines concerned by the procedure – medicine(s) / active substance(s) concerned, and marketing authorisation holder(s) / applicant(s)
• List of questions to be addressed by the stakeholders – call for data to be submitted by stakeholders (e.g. healthcare professionals, patient organisations, individual patients) (if applicable)
• Stakeholder submission form – form to be used by stakeholders to submit data (if applicable)
• Scientific conclusions – scientific conclusions of the PRAC and/or CHMP and/or CMDh
• Assessment report – PRAC or CHMP assessment and conclusions on the issues investigated, including divergent positions (if applicable)
• Divergent positions – divergent positions of the CHMP or CMDh members for pharmacovigilance procedures (if applicable)
• Changes to the summary of product characteristics, labelling and package leaflet (amended sections or fully revised version) (if applicable)
• Condition(s) to the marketing authorisation(s) – condition(s) for the safe and effective use of the medicine(s) (if applicable)
• Condition for lifting the suspension – condition to be fulfilled for the suspension of the marketing authorisation(s) to be lifted (if applicable)
• Timetable for implementation of CMDh position – agreed timeframe to submit and finalise the variation(s) implementing the outcome of the procedure (if applicable)

Note that older documents may have different titles.