Methadone medicinal products for oral use containing povidone

  • Procedure started
  • Under evaluation
  • PRAC recommendation
  • CMDh position
  • European Commission final decision
Current status:
Position provided by CMDh

Overview

CMDh endorses suspension of methadone oral solutions containing high molecular weight povidone

The Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh)1 has endorsed by consensus the recommendation to suspend the marketing authorisation of methadone oral (by mouth) solutions containing high molecular weight povidone. These products will remain suspended until they have been reformulated. Additionally, the CMDh agreed that methadone tablets that contain low molecular weight povidone should remain on the market with changes to the product information.

Methadone is used in rehabilitation programs to prevent or reduce withdrawal symptoms in patients dependent on opioids such as heroin. Some oral formulations of methadone also contain the additive povidone, which is available in different molecular weights. While these medicines are intended for oral use only, some patients may misuse oral methadone formulations by injecting them into a vein. If a medicine containing high molecular weight povidone (known as K90) is misused in this way, the povidone is not excreted from the body and accumulates inside the cells of vital organs, which may cause serious harm.

The safety of oral methadone medicines containing povidone was reviewed by the EMA's Pharmacovigilance Risk Assessment Committee (PRAC), following reports of serious adverse events in former or current drug abusers in Norway, which led to the suspension of methadone oral solutions containing povidone K90 from the Norwegian market.

The PRAC assessed the available safety data on the risks associated with the misuse by injection of methadone medicines containing povidone from post-marketing reports and the published literature, and a group of experts (which included pathologists and addiction experts) was consulted for advice. The PRAC concluded that risk minimisation measures would be insufficient to mitigate the risks with oral solutions containing high molecular weight povidone, and therefore recommended that these products should be suspended. They will need to be appropriately reformulated before being reintroduced on the European market.

For methadone tablets containing povidone of lower molecular weight (e.g. K25 and K30), the available data showed that this kind of povidone is excreted from the body and does not accumulate inside the cells as high molecular weight povidone does. Therefore, these products will remain on the market and changes will be made to the product information (SmPC and package leaflet) to reinforce the message that tablets are for oral administration only and must not be taken in any other way.

As the PRAC recommendation was endorsed by consensus by the CMDh, it will now be implemented in all EU Member States where these medicines are marketed, according to an agreed timetable.


1 The CMDh is a medicines regulatory body representing the European Union (EU) Member States.

Key facts

About this medicine
Approved name
Methadone medicinal products for oral use containing povidone
International non-proprietary name (INN) or common name
methadone
About this procedure
Current status
Position provided by CMDh
Reference number
EMEA/H/A-107i/1395
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.

Decision making model
PRAC-CMDh
Authorisation model
Nationally authorised product(s)
Key dates and outcomes
Procedure start date
10/04/2014
PRAC recommendation date
10/07/2014
CHMP opinion/CMDh position date
23/07/2014
Outcome
Suspension

Data submission

The Agency invites all stakeholders (e.g. healthcare professionals, patients' organisations and 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 specific PDF iconprivacy 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

Recommendation provided by Pharmacovigilance Risk Assessment Committee

Position provided by CMDh

  • List item

    CMDh endorses suspension of methadone oral solutions containing high molecular weight povidone (PDF/80.05 KB)


    First published: 24/07/2014
    Last updated: 24/07/2014
    EMA/444346/2014

  • List item

    Methadone Article-107i procedure - Annex IV (PDF/46.37 KB)


    First published: 04/08/2014
    Last updated: 04/08/2014

  • List item

    Methadone Article-107i procedure - Annex II (PDF/80.08 KB)


    First published: 04/08/2014
    Last updated: 04/08/2014

  • List item

    Methadone Article-107i procedure - PRAC assessment report (PDF/228.93 KB)

    Adopted

    First published: 04/08/2014
    Last updated: 04/08/2014
    EMA/464317/2014

  • List item

    Methadone Article-107i procedure - Annex V (PDF/32.7 KB)


    First published: 04/08/2014
    Last updated: 04/08/2014

  • List item

    Methadone Article-107i procedure - Annex I (PDF/84.27 KB)


    First published: 04/08/2014
    Last updated: 04/08/2014

  • List item

    CMDh endorses suspension of methadone oral solutions containing high molecular weight povidone (PDF/80.05 KB)


    First published: 24/07/2014
    Last updated: 24/07/2014
    EMA/444346/2014

  • List item

    Methadone Article-107i procedure - Annex III (PDF/11.38 KB)


    First published: 24/07/2014
    Last updated: 24/07/2014

  • Document description

    • Annex I - List of the medicines affected by the referral
    • Annex II - Scientific conclusions of the CHMP or CMDh
    • Annex III - Changes to the summary of product characteristics, labelling or package leaflet - available when the CHMP or CMDh recommends changes to the product information. Also includes conditions for lifting of suspensions, if applicable
    • Annex IV - Conditions of the marketing authorisation - available when the CHMP or CMDh recommends other measures to be taken for the marketing authorisation such as safety measures or additional studies
    • Notification - A letter from a Member State, the European Commission or a marketing-authorisation holder requesting the initiation of a referral procedure
    • Rationale for triggering - Background provided by the party triggering the referral explaining the issues leading to the initiation of the procedure
    • PRAC list of questions - Questions agreed by the PRAC requesting further information to evaluate the issues identified
    • PRAC timetable - Timeframe agreed by the PRAC to receive information, assess the issues and adopt a recommendation
    • PRAC / CHMP or CMDh assessment report - The assessment and conclusions of the PRAC and CHMP or CMDh on the issues investigated

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