On amending the package inserts for medicinal products containing choline salicylate / cetalkonium chloride (cetalkonium / choline salicylate)

In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.

The Pharmacovigilance Risk Assessment Committee (PRAC), based on the assessment of periodic safety update reports (PSURs) for medicinal products containing choline salicylate and cetalkonium chloride (cetalkonium / choline salicylate), PSUSA/00000626/202508, reached the following conclusions.

In view of the available data on medicinal products of the same therapeutic class, and also taking into account the likely mechanism of action, it is considered necessary to introduce a warning about the risk of using choline salicylate / cetalkonium chloride during pregnancy.

In addition, based on available data from a literature source, it is considered necessary to introduce a warning regarding use by patients who currently suffer from peptic ulcer or have a history of it.

Also, taking into account the available data for the therapeutic class of salicylates and the risk of salicylate poisoning, introducing a warning on the concomitant use of other salicylates is considered relevant.

The PRAC concluded that the instructions for medical use of medicinal products containing choline salicylate / cetalkonium chloride should be updated accordingly.

Having considered the PRAC recommendations, the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) agrees with the overall conclusions of the PRAC and the grounds for the recommendations.

Based on the scientific conclusions on choline salicylate / cetalkonium chloride, CMDh considers that the benefit/risk balance of medicinal products containing choline salicylate / cetalkonium chloride remains unchanged, provided that the proposed amendments to the instructions for medical use are made.

Changes to be made to the relevant sections of the instructions for medical use (new text is underlined and in bold).

“Special precautions for use” section

This medicinal product contains salicylate and should not be used together with aspirin or other salicylates, unless prescribed by a doctor or dentist.

This medicinal product should be used with caution in patients with active or recurrent gastric or duodenal ulcer.

Section “Use during pregnancy or breastfeeding”

There are no clinical data on the use of [medicinal product name] during pregnancy. Although systemic exposure after topical administration is lower than after oral administration, it is not known whether the level of systemic exposure to [medicinal product name] achieved after buccal administration may have a harmful effect on the embryo/fetus.

During the first and second trimesters of pregnancy, [name of the medicinal product] should be used only in case of absolute necessity. If use is necessary, the dose should be as low as possible and the duration of treatment as short as possible.

In the third trimester of pregnancy, systemic use of prostaglandin synthetase inhibitors, including [name of the medicinal product], may cause the development of cardiopulmonary and renal toxicity in the fetus. At the end of pregnancy, bleeding time may be prolonged in both the mother and the newborn, and the onset of labor may be delayed. Therefore, [name of the medicinal product] should not be used in the third trimester.

Changes to the safety information for medicinal products containing choline salicylate / cetalkonium chloride (cetalkonium / choline salicylate), based on the results of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of March 09 – 12, 2026

The European Medicines Agency (EMA) has published the minutes of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 09 – 12 March 2026. Following the meeting, a decision was made on the need to introduce safety-related changes to the registration materials/instructions for medical use of medicinal products containing choline salicylate / cetalkonium chloride (cetalkonium / choline salicylate).

Choline salicylate / cetalkonium chloride (cetalkonium / choline salicylate) – PSUSA/00000626/202508

Choline salicylate is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic and analgesic properties. Cetalkonium chloride has antibacterial and antifungal action. The combination of cetalkonium and choline salicylate is used for fast relief of pain, inflammation and discomfort associated with mouth ulcers, irritation from dentures, and sore areas caused by the use of orthodontic appliances.

Based on the assessment of periodic safety update reports (PSURs), PRAC reviewed the benefit/risk balance of the use of medicinal products containing choline salicylate / cetalkonium chloride (cetalkonium / choline salicylate) and provided the relevant recommendations.

Summary of recommendations and conclusions

• Based on the analysis of safety and efficacy data, the benefit/risk balance of medicinal products containing choline salicylate / cetalkonium chloride (cetalkonium / choline salicylate), for the approved indications remains unchanged.
• At the same time, the instructions for medical use should be updated to add a warning about the risk of using aspirin or other medicinal products containing salicylates, as well as a warning regarding use in patients who currently have or have had a history of peptic ulcer disease, and to supplement the information on use during pregnancy. Thus, the current provisions of the instructions for medical use must be amended¹.
• In the next PSUR, the applicant(s) must identify similar safety concerns based on the list proposed by the applicant Reckitt, with some adjustments as needed: immune system reactions / hypersensitivity reactions, use in the third trimester of pregnancy or during breastfeeding, and Reye's syndrome as important identified risks; concomitant use of acetylsalicylic acid or other salicylates, use beyond the recommended maximum duration, which may delay the treatment of more serious underlying diseases, off-label use in children under 4 months, and use during the first and second trimesters of pregnancy as important potential risks; missing information – none. The applicant(s) must also closely monitor any cases or new information regarding bronchospasm and asthma. The applicants Lavipharm and Pierre Fabre must closely monitor any cases or any new information related to the drug interaction with uricosuric agents.

________________________________________________________________

¹Update of the sections “Special warnings and precautions for use” and “Use during pregnancy or breastfeeding” of the instructions for medical use. The risk assessment report and the PRAC recommendation are forwarded to the CMDh for a decision.

TO ANALYZE THE PUBLISHED INFORMATION AND SUBMIT THE RELEVANT APPLICATION FOR AMENDMENTS TO THE REGISTRATION MATERIALS, THE APPLICANT MUST USE THE ORIGINAL TEXT AVAILABLE AT THE FOLLOWING LINKS: