Pholcodine-containing medicinal products

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision

Table of contents

Current status
European Commission final decision

Overview

Pholcodine medicines withdrawn from EU market

On 1 December 2022, EMA’s safety committee, PRAC, concluded its review of medicines containing pholcodine, which are used in adults and children to treat non-productive (dry) cough and, in combination with other active substances, for the treatment of symptoms of cold and flu, and recommended the revocation of the EU marketing authorisations for these medicines.

During the review, the PRAC evaluated all available evidence including the final results of the ALPHO study,1 post-marketing safety data and information submitted by third parties such as healthcare professionals. The available data showed that use of pholcodine in the 12 months before general anaesthesia with neuromuscular blocking agents (NMBA) is a risk factor for developing an anaphylactic reaction (a sudden, severe and life-threatening allergic reaction) to NMBAs.

As it was not possible to identify effective measures to minimise this risk, nor to identify a patient population for whom the benefits of pholcodine outweigh its risks, pholcodine-containing medicines are being withdrawn from the EU market and will therefore no longer be available by prescription or over-the-counter.

Healthcare professionals should consider appropriate treatment alternatives and advise patients to stop taking pholcodine-containing medicines. Healthcare professionals should also check whether patients scheduled to undergo general anaesthesia with NMBAs have used pholcodine in the previous 12 months, and remain aware of the risk of anaphylactic reactions in these patients.

The PRAC recommendations were sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh),2 which endorsed them and adopted its position on 14 December 2022. 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 6 March 2023.

1 Companies marketing pholcodine medicines were requested to conduct the ALPHO study following a previous safety review conducted in 2011.

2 The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.

Key facts

About this medicine
Approved name
Pholcodine-containing medicinal products
International non-proprietary name (INN) or common name
pholcodine
Class
Cough and cold preparations
About this procedure
Current status
European Commission final decision
Reference number
EMEA/H/A-107i/1521
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
01/09/2022
PRAC recommendation date
01/12/2022
CHMP opinion/CMDh position date
14/12/2022
EC decision date
06/03/2023
Outcome
Revocation

Data submission

The Agency invites all stakeholders (e.g. healthcare professionals, patients' organisations, the general public) to submit data relevant to this procedure. This is in accordance with Article 107j(1) of Directive 2001/83/EC.

The following requirements apply for data to be considered:

Submitting data

Send the completed form electronically to the stakeholders' submission inbox (public@ema.europa.eu). Specify the name of the medicine in the subject line of the e-mail.

The size of the submission file should not exceed 25 MB. If your attempt to send your data package to the dedicated e-mail address is unsuccessful, please use alternative submission means.

It is of the utmost importance that data are provided promptly, to avoid undermining the safety review. Due to the urgent nature of the procedure, you are strongly advised to submit your data in English.

Protection of personal data

Personal data submitted are subject to data-protection rules as established by Regulation (EC) 45/2001. They will be treated in accordance with the PDF icon specific privacy statement for public consultations .

Treatment and publication of data

Data submitted will be received and recorded by the Agency.

The Agency will prepare a list of all submissions received, which will be published as an annex to the PRAC assessment report for transparency purposes and public awareness.

Please note that all data submitted in the context of this procedure may be shared and disclosed in the public domain.

All documents

Procedure started

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Rationale for triggering (PDF/840.8 KB)


    First published: 02/09/2022

  • List item

    Pholcodine-containing medicinal products Article-107i referral - List of questions to marketing authorisation holder(s) (PDF/268.1 KB)


    First published: 02/09/2022
    EMA/PRAC/704708/2022

  • List item

    Pholcodine-containing medicinal products Article-107i referral - List of questions to stakeholders (PDF/120.29 KB)


    First published: 02/09/2022
    EMAP/PRAC/709548/2022

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Stakeholders submission form (PDF/28.7 KB)


    First published: 02/09/2022

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Timetable for the procedure (PDF/117.07 KB)


    First published: 02/09/2022
    EMA/PRAC/704846/2022

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Annex I (PDF/129.33 KB)

    Draft

    First published: 02/09/2022
    Last updated: 04/10/2022
    EMA/722200/2022 Rev. 1

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Notification (PDF/68.09 KB)


    First published: 02/09/2022

    • Recommendation provided by Pharmacovigilance Risk Assessment Committee

    Position provided by CMDh

    European Commission final decision

  • List item

    Pholcodine medicines withdrawn from EU market (PDF/100.64 KB)


    First published: 29/03/2023
    EMA/126062/2023

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Annex II (PDF/101.67 KB)


    First published: 29/03/2023

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Annex I (PDF/68.98 KB)


    First published: 29/03/2023

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Divergent positions to CMDh position (PDF/78.37 KB)

    Adopted

    First published: 22/03/2023

  • List item

    Pholcodine-containing medicinal products Article-107i referral - Assessment report (PDF/293.7 KB)

    Adopted

    First published: 22/03/2023
    EMA/950036/2022

    • 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.

    News

    Direct healthcare professional communications (DHPC)

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