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 analysis of Periodic Safety Update Reports (PSURs) for medicinal products containing nefopam, PSUSA/00002131/202503, reached the following conclusions.
In view of the available literature data and spontaneous reports, the PRAC considers that a causal relationship between the use of nefopam and the development of drug dependence is at least reasonably possible. The PRAC concluded that the instructions for medical use of medicinal products containing nefopam should be amended 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 nefopam, the CMDh considers that the benefit/risk balance of medicinal products containing nefopam does not change, provided that the proposed changes are made to the instructions for medical use.
Changes to be made to the relevant sections of the instruction for medical use (new text underlined and in bold, deleted text struck through).
“Special precautions for use” section
The warning should be changed as follows (the existing wording under the relevant topic should be replaced with the paragraph below, if necessary):
Cases of dependence and abuse have been reported with the use of nefopam.
Drug dependence
The use of nefopam may lead to the development of drug dependence, which can result in drug abuse, especially in patients with a history of psychoactive substance use and/or mental disorders. Nefopam should be prescribed with caution to such patients, and they should be monitored for signs of dependence.
“Adverse reactions” section
The following adverse reaction should be added to the System Organ Class (SOC) “Psychiatric disorders”: Preferred Term (PT) “Drug dependence” with the frequency “rare”.
The following paragraph should be added below the table or the description of adverse reactions:
Drug dependence
The use of [name of the medicinal product] may lead to the development of drug dependence. The risk of developing drug dependence may vary depending on the patient’s individual risk factors (see section “Special precautions for use”).
Changes to the safety information on nefopam-containing medicinal products based on the results of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 24 – 27 November 2025
The European Medicines Agency (EMA) has published the minutes of the Pharmacovigilance Risk Assessment Committee (PRAC) meeting of 24 – 27 November 2025. 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 nefopam.
Nefopam – PSUSA/00002131/202503
Nefopam is a non-narcotic analgesic that, in the form of a solution for injection, is used for the symptomatic treatment of acute pain conditions, while oral forms of nefopam are used to relieve acute and chronic pain, including postoperative, dental and musculoskeletal pain, acute trauma and pain associated with cancer.
Based on the assessment of periodic safety update reports (PSURs), the PRAC reviewed the benefit/risk balance of medicinal products containing nefopam and made 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 nefopam for the approved indications remains unchanged.
- At the same time, the instruction for medical use should be updated to amend the warning on drug dependence and to add drug dependence as an adverse reaction with the frequency “rare”. Thus, the existing provisions of the instruction for medical use should be amended1.
- In the next PSUR, all registration certificate holders must provide a cumulative analysis of cases of drug interaction between nefopam and serotonin and norepinephrine reuptake inhibitors (including venlafaxine), as well as between nefopam and selective serotonin reuptake inhibitors (including sertraline), taking into account data from the scientific literature.
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1Update of the “Special warnings and precautions for use” and “Adverse reactions” sections of the instructions for medical use. The risk assessment report and the PRAC recommendation are forwarded to CMDh for decision.
List of medicinal products containing nefopam and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 31.03.2026). (14 KB) (Downloaded: 06.04.2026 06:29:02)
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:
