Amfepramone-containing medicinal products - referral

Current status

European Commission final decision

Overview

Withdrawal of marketing authorisations for amfepramone medicines within the EU

On 27 October 2022, EMA’s safety committee (PRAC) confirmed its recommendation to withdraw the marketing authorisations for amfepramone obesity medicines. This followed a re-examination of its previous recommendation of June 2022, which was requested by the companies that market these medicines.

The recommendation followed a review which found that measures to restrict the use of these medicines for safety reasons have not been sufficiently effective. It found that the medicines were being used for longer than the recommended maximum period of 3 months, thereby potentially increasing the risk of serious side effects such as pulmonary arterial hypertension (high blood pressure in the lungs) and dependency. The medicines were also being used in patients with a history of heart disease or psychiatric disorders, increasing their risk of heart and psychiatric problems. In addition, there was evidence of use during pregnancy, which could pose risks to the unborn baby. 

The review considered all available information relating to these concerns, including data from two studies on the use of amfepramone medicines in Germany and in Denmark. In addition, the PRAC received advice from a group of experts, comprising endocrinologists, cardiologists and a patient representative. 

The PRAC considered introducing further measures to minimise the risk of side effects but could not identify any that would be sufficiently effective. The PRAC therefore concluded that the benefits of amfepramone medicines do not outweigh their risks and recommended that the medicines be removed from the market in the EU.

The CMDh¹ agreed with the PRAC recommendation and adopted its position by majority on 10 November 2022. The CMDh position was forwarded to the European Commission, which issued a final legally binding decision on 13 January 2023 that is applicable in all EU countries.

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¹ Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human

Information for patients

• EMA recommended that amfepramone obesity medicines should no longer be available because they are not always used as recommended. 
• Inappropriate use can cause serious side effects, such as increased blood pressure in the arteries of the lungs, heart disease, dependency, psychiatric problems and harm to the unborn baby. 
• In addition, the benefits of using these medicines in the treatment of obesity are considered limited. 
• Other obesity treatment options are available. Contact your doctor to discuss which treatment would be suitable for you. 
• If you have other questions or concerns about amfepramone medicines, speak to your doctor or pharmacist.

Information for healthcare professionals

• EMA recommended the withdrawal of the EU marketing authorisations for amfepramone medicines for the treatment of obesity.
• A review of available data  found that amfepramone medicines continue to be used outside the current risk minimisation measures included in the product information. 
• Inappropriate use may increase the risk of serious adverse effects, including cardiovascular disease, pulmonary arterial hypertension, dependency and psychiatric disorders, as well as harmful effects if used during pregnancy.
• A review of available data also indicated that the efficacy of amfepramone in the treatment of obesity is limited.
• Healthcare professionals should advise patients about other treatment options.

A direct healthcare professional communication (DHPC) will be sent in due course to healthcare professionals prescribing or dispensing the medicine and published on a dedicated page on the EMA website.

More about the medicine

Amfepramone is a sympathomimetic, which means that it acts in the brain and causes effects that are similar to those of adrenaline. Such medicines reduce a feeling of hunger. 

Amfepramone medicines were authorised in Denmark, Germany and Romania as treatment for patients with obesity (body mass index of at least 30 kg/m²) in whom other weight-reduction methods have not worked on their own. Amfepramone medicines were authorised to be used for 4 to 6 weeks and no longer than 3 months.

Within the EU, amfepramone medicines are available under the following trade names: Amfepramon Hormosan 25 mg Weichkapseln, Amfepramon Hormosan 60 mg Retardkapseln, Regenon, Tenuate Retard 75 mg retardtablette and Regenon 25 mg capsule moi.

More about the procedure

The review of amfepramone medicines was initiated at the request of the Romanian medicines agency (NAMMDR), under Article 31 of Directive 2001/83/EC.

The review was carried out by the Pharmacovigilance Risk Assessment Committee (PRAC), the Committee responsible for the evaluation of safety issues for human medicines, which has made a set of recommendations. Following a re-examination requested by the marketing authorisation holders, the PRAC subsequently confirmed its conclusions for amfepramone-containing medicines.

Because these medicines are all authorised at national level, the PRAC recommendations were sent to the CMDh, which has adopted a position. 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 across the EU. As the CMDh position was adopted by majority vote, it was sent to the European Commission, which issued a final legally binding decision applicable in all EU Member States on 13 January 2023.

This review follows Amfepramone-containing medicinal products Article-31 referral - Notification on the benefits and risks of appetite-suppressing medicines (including amfepramone) in 1996 and 1999.

Amfepramone-containing medicinal products Article-31 referral - Withdrawal of marketing authorisations for amfepramone medicines within the EU

Reference Number: EMA/867253/2022

Key facts

About this medicine

• Approved name:
  Amfepramone-containing medicinal products
• International non-proprietary name (INN) or common name:
  amfepramone
• Associated names:
  • Regenon
  • Tenuate Retard
  • Amfepramon-Hormosan
  • Regenon Retard

About this procedure

• Current status:
  European Commission final decision
• Reference number:
  EMEA/H/A-31/1501
• Type:
  Article 31 referrals

  This type of referral is triggered when the interest of the Union is involved, following concerns relating to the quality, safety or efficacy of a medicine or a class of medicines.

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

Key dates and outcomes

• Procedure start date:
  11/02/2021
• PRAC recommendation date:
  27/10/2022
• CMDh position date:
  10/11/2022
• EC decision date:
  13/01/2023
• Outcome:
  Revocation

All documents

Procedure started

Amfepramone-containing medicinal products Article-31 referral - Notification

Amfepramone-containing medicinal products Article-31 referral - Annex I

Reference Number: EMA/91464/2021

Amfepramone-containing medicinal products Article-31 referral - PRAC list of questions

Reference Number: EMA/PRAC/51715/2021

Under evaluation

Amfepramone-containing medicinal products Article-31 referral - Timetable for the procedure

Reference Number: EMA/PRAC/51714/2021 Rev.5

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Amfepramone-containing medicinal products Article-31 referral - EMA recommends withdrawal of marketing authorisation for amfepramone medicines

Reference Number: EMA/844036/2022

Position provided by CMDh

Amfepramone-containing medicinal products Article-31 referral - Withdrawal of marketing authorisations for amfepramone medicines within the EU

Reference Number: EMA/867253/2022

European Commission final decision

Amfepramone-containing medicinal products Article-31 referral - Annex I

Amfepramone-containing medicinal products Article-31 referral - Annex II

Amfepramone-containing medicinal products Article-31 referral - Assessment report

Reference Number: EMA/884474/2022

Amfepramone-containing medicinal products Article-31 referral - Divergent positions to CMDh position

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.