News Category: Regulatory news
HPRA commences formal regulatory procedure
The HPRA, as the competent authority for determining the method of sale for individual medicines, has commenced a formal regulatory procedure to determine the appropriate method of sale for authorised codeine-containing medicines in Ireland. In general, method of sale refers to the classification of a medicine as either prescription-only or over the counter (OTC). Currently, codeine-containing medicines are available in Ireland OTC through pharmacies and are not subject to medical prescription.
The commencement of this formal procedure is the latest phase in an ongoing HPRA review of the use and classification of these products. This review, which commenced in quarter two of 2022, involves evaluating the available supporting evidence and experience of use for codeine-containing medicines accrued nationally and from other EU and international markets. The review is also being informed by ongoing engagement with relevant national and international stakeholders.
In recent years, a number of jurisdictions have reviewed the method of sale for codeine-containing products in response to a growing understanding of the potential impacts of addiction to codeine in low doses. In Ireland, this has been addressed to date by restricting access to codeine-containing products through pharmacies. While codeine-containing medicines are also similarly available without prescription in some other countries, in certain other jurisdictions they are available solely via a prescription from a doctor.
Commencement of formal regulatory procedure
As part of the HPRA’s ongoing review of codeine-containing products, the HPRA has today commenced a formal regulatory procedure to determine the appropriate method of sale for authorised codeine-containing products^. Under this formal procedure*, all marketing authorisation holders (MAHs) have been invited to submit data supporting the method of sale specific to their product. This is the next step in the HPRA’s review process. All of the available data must now be carefully considered within this context to determine whether any necessary regulatory actions are required to support the safe and effective use of these medicines.
Consistent with all regulatory procedures, the ongoing assessment of this matter, as well as any data received and reviewed by the HPRA, will remain confidential until the outcome is determined. The timescale for the procedure will be dependent on the availability of information from external sources. Once the procedure is completed, the HPRA will communicate the outcome and any recommendations to all relevant stakeholders.
HPRA-initiated EU safety review
In parallel with this ongoing review of the method of sale for codeine-containing products in Ireland, the European Medicines Agency (EMA) safety committee (PRAC) recently concluded a review of new safety concerns relating to codeine with ibuprofen combination medicines**. This review was triggered and led by the HPRA as part of its membership of PRAC. It has resulted in recommendations to update the product information for codeine with ibuprofen combination medicines to include stronger warnings of serious harms, including death, particularly when taken for prolonged periods at higher than recommended doses.
The PRAC’s recommendations were published by the EMA at the end of September. Following the conclusion of the PRAC review, the HPRA has communicated with healthcare professionals to raise awareness of the serious clinical harms associated with prolonged use of these medicines at higher than recommended doses due to codeine dependence and to inform them of the PRAC’s recommendations including the updates to the product information.
Furthermore, the PRAC recommendations also stated that the most effective way to reduce the risk of harm associated with abuse and dependence of these products is to make them available only with a prescription. This recommendation will also be considered as part of the HPRA’s formal regulatory procedure to determine the appropriate method of sale.
Current availability and recommendations for use
Over-the-counter codeine-containing medicines, including those in combination with ibuprofen or with paracetamol, are currently available in Ireland without prescription, under pharmacist supervision. These medicines are used for the short-term treatment of acute, moderate pain that is not relieved by paracetamol or ibuprofen alone. Other codeine containing products available without prescription in Ireland include a liquid preparation to supress coughing.
The existing product packaging and patient information leaflet, which accompany codeine-containing medicines, already contains detailed advice on known warnings and side effects associated with these products. The warnings for codeine-containing medicines in combination with ibuprofen or with paracetamol state that these medicines should be used at the lowest effective dose for the shortest period of time, the duration of treatment should be limited to three days and, if no effective pain relief is achieved, the patient should be advised to seek the opinion of their doctor. The current product information for all codeine-containing medicines in particular highlights that codeine can cause addiction if taken continuously for more than three days.
The HPRA recommends that patients always take time to read the accompanying patient information leaflet that comes with every medicine and that they follow the dosage and duration of use instructions. Patients should seek further advice from a healthcare professional if they have any queries or concerns about their medicine.
Any suspected adverse reactions associated with the use of medicines, including those containing codeine, may be reported to the HPRA through the available reporting options (www.hpra.ie/report).
Further information
* Formal Regulatory Procedure
The HPRA has commenced a formal regulatory classification procedure under Article 74 of Directive 2001/83/EC, as amended, of all over the counter products containing codeine.
^ Codeine-containing medicines currently authorised
Based on the most recent information available the products below are both authorised and currently marketed in Ireland:
The below products are authorised but not known to be currently marketed in Ireland based on the most recent information provided to the HPRA by the licence holder:
** EMA Safety Review
Further information relating to the outcome of the EMA’s safety review of codeine with ibuprofen combination medicines:
The HPRA approved a communication from the MAHs/licence holders to relevant healthcare professionals in Ireland to communicate the outcome of the PRAC review and associated recommendations. It is published on the HPRA website:
Media queries
Káno Communications (01) 679 8600
Siobhán Molloy / Kathryn Moley (086) 817 5066 / (086) 733 4438