Pholcodine-containing medicinal products

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

Overview

The European Medicines Agency (EMA) has started a review of medicines that contain pholcodine following concerns that their use may put people at risk of developing anaphylactic reactions (a sudden, severe and life-threatening allergic reaction) to certain medicines called neuromuscular blocking agents (NMBA). Pholcodine is used to treat non-productive (dry) cough in adults and children and NMBAs are used in general anaesthesia to prevent spontaneous muscle movements to improve operating conditions.

The review was requested by the French medicines agency (ANSM) following preliminary results of a study (ALPHO) carried out in France1. The results of the study suggested that taking pholcodine up to 12 months before general anaesthesia may increase the risk of having an NMBA-related anaphylactic reaction. Based on these results ANSM is considering, as a precautionary measure, to suspend the use of pholcodine-containing medicines in France.

The ALPHO study was carried out as a condition to the marketing authorisations of pholcodine-containing medicines following a previous safety review in 2011. At the time, the Agency's Committee for Medicinal Products for Human Use (CHMP) found no firm evidence that use of pholcodine may put people at risk of developing anaphylactic reactions to NMBAs and recommended that a new study (the ALPHO study) should be carried out to investigate this risk in people taking pholcodine.

While ALPHO study was ongoing, in 2021, a study in Australia2 linked pholcodine’s use to an increased risk of anaphylaxis to NMBA muscle relaxants. This led to a recommendation by PRAC to include relevant warnings in the product information of pholcodine-containing medicines.

The PRAC will now review the results of the ALPHO study together with all available data and assess their impact on the benefit-risk balance of pholcodine-containing medicines and issue a recommendation on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the EU.

The Agency invites all stakeholders (e.g. healthcare professionals, patients’ organisations, the general public) to submit data relevant to this procedure. Full details are available in the  PDF icon Stakeholder submission form  (please view in Adobe Reader X+ or Adobe Acrobat X+).


1Allergy to Neuromuscular Blocking Agents and Pholcodine Exposure (ALPHO)

2Sadleir et al. Relationship of perioperative anaphylaxis to neuromuscular blocking agents, obesity, and pholcodine consumption: a case-control study. Br J Anaesth (2021) May;126(5):940-948. doi: 10.1016/j.bja.2020.12.018. Epub 2021 Jan 14.

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
Procedure started
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

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

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.

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