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 Pharmacovigilance Risk Assessment Committee (PRAC) meeting of 27 – 30 October 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 clozapine.
Clozapine – PSUSA/00000836/202503
Clozapine is an atypical antipsychotic indicated for the treatment of patients with treatment-resistant schizophrenia or patients with intolerance to other antipsychotics, as well as for the treatment of psychotic disorders in Parkinson's disease in cases where standard therapy is ineffective.
Based on the assessment of Periodic Safety Update Reports (PSURs), PRAC reviewed the benefit/risk balance of medicinal products containing clozapine 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 clozapine for the approved indications remains unchanged.
- At the same time, the instructions for medical use should be updated by adding a warning about the risk of appendicitis associated with the anticholinergic action of clozapine, and including appendicitis as an adverse reaction with the frequency “not known,” as well as adding hematological malignancies as an adverse reaction with the frequency “not known.” In addition, the instructions for medical use should be updated by adding a warning about the risk of drug reaction with eosinophilia and systemic symptoms (DRESS) and including drug interaction with valproic acid and the associated increased risk of myocarditis caused by the use of clozapine. Accordingly, the existing provisions of the instructions for medical use should be amended1.
- In the next PSUR, registration certificate holders must provide cumulative reviews of cases of eosinopenia, hypogammaglobulinemia, hypothermia and related events, as well as of the interaction between the use of clozapine and tobacco smoking, including pharmacokinetic and therapeutic drug monitoring data, as well as clinical consequences, if available.
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1Update of the sections “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 PRAC recommendation are forwarded to the CMDh for decision.
List of medicinal products containing clozapine and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 13.04.2026). (9.8 KB) (Downloaded: 16.04.2026 06:24:11)
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:
