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 European Medicines Agency (EMA) has published the minutes of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 12 – 15 January 2026. Based on the results of the meeting, a decision was made on the need to introduce safety-related amendments to the registration materials/instructions for medical use of medicinal products containing caffeine/codeine/paracetamol/propyphenazone and acetylsalicylic acid/caffeine/codeine/paracetamol.
Caffeine/codeine/paracetamol/propyphenazone and acetylsalicylic acid/caffeine/codeine/paracetamol – PSUSA/00002312/202506
Caffeine/codeine/paracetamol/propyphenazone and acetylsalicylic acid/caffeine/codeine/paracetamol are fixed-dose combinations that are usually used for short-term symptomatic treatment of moderate or severe pain (depending on the medicinal product), especially in cases where such pain is not sufficiently relieved by analgesics such as paracetamol or ibuprofen used alone. In addition, acetylsalicylic acid/caffeine/codeine/paracetamol is indicated for symptomatic treatment of fever and inflammatory processes of the upper respiratory tract accompanied by cough and fever.
Based on the evaluation of periodic safety update reports (PSURs), PRAC reviewed the benefit/risk ratio of the use of medicinal products containing caffeine/codeine/paracetamol/propyphenazone (caffeine/codeine/paracetamol/propyphenazone) and acetylsalicylic acid/caffeine/codeine/paracetamol (acetylsalicylic acid/caffeine/codeine/paracetamol), and provided relevant recommendations.
Summary of recommendations and conclusions
- Based on the analysis of safety and efficacy data, the benefit/risk balance of medicinal products containing caffeine/codeine/paracetamol/propyphenazone and acetylsalicylic acid/caffeine/codeine/paracetamol remains unchanged for the approved indications.
- At the same time, the instructions for medical use should be updated by adding warnings regarding central sleep apnea (CSA), hyperalgesia, hepatobiliary disorders, Kounis syndrome and information related to tolerance and opioid use disorders (OUD) (abuse and dependence), as appropriate. In addition, the instructions for medical use should be updated by adding information on drug interaction with gabapentinoids, and by including pancreatitis, sphincter of Oddi dysfunction and Kounis syndrome as adverse reactions with a frequency of “not known”. Thus, the existing provisions of the instructions for medical use must be amended1.
- In the next PSUR, registration certificate holders must update the list of safety concerns considered in the report and state the following in it: opioid toxicity (respiratory depression and sedation) and disorders associated with the use of opioids (abuse, misuse, dependence, addiction, tolerance, withdrawal syndrome) as important identified risks; effect on fertility as missing information.
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1Update of the sections “Method of administration and doses,” “Special warnings and precautions for use,” “Interaction with other medicinal products and other forms of interaction,” and “Adverse reactions” of the instructions for medical use. The risk assessment report and the PRAC recommendation are forwarded to the CMDh for decision-making.
List of medicinal products containing caffeine/codeine/paracetamol/propyphenazone and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 31.03.2026). (13 KB) (Downloaded: 10.04.2026 09:31:10)
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:
