In accordance with paragraph 8 of Section IV of the Procedure for Conducting Expert Evaluation, the applicant must make amendments to 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 must ensure that the information on the medicinal product is consistent with current scientific knowledge.
The European Medicines Agency (EMA) has published the minutes of the meeting of the Pharmacovigilance Risk Assessment Committee (PRAC) of 06 – 09 July 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 enfortumab vedotin.
Enfortumab vedotin (enfortumab vedotin) – PADCEV – PSUSA/00010989/202512
Based on the evaluation of periodic safety update reports (PSURs), the PRAC reviewed the benefit / risk balance of the use of the medicinal product PADCEV (enfortumab vedotin) and provided the relevant recommendations.
Summary of recommendations and conclusions
- Based on the analysis of safety and efficacy data, the benefit / risk balance of the medicinal product PADCEV (enfortumab vedotin) for the approved indications remains unchanged.
- At the same time, the instructions for medical use should be updated by adding opportunistic infections, in particular fungal infection, as an adverse reaction with a frequency of “unknown” for both monotherapy and use in combination with pembrolizumab. In addition, the instructions for medical use should be updated by adding leukopenia and urinary tract infections as adverse reactions with frequencies of “common” and “very common”, respectively, for both monotherapy and use in combination with pembrolizumab. Thus, the current instructions for medical use should be updated accordingly1.
- In the next PSUR, the registration certificate holder (RCH) should present new cases of pyelonephritis, lymphopenia, drug-induced eosinophilia with systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). In addition, the RCH should provide cumulative reviews of cases of insulin resistance and insulin-resistant diabetes mellitus, as well as cardiotoxicity with an emphasis on arrhythmia, heart failure, coronary heart disease, and myocarditis. These reviews should include a review of the published literature, spontaneous report data, and a discussion of the possible biological plausibility and mechanism of this association. The RCH should also discuss the need to make any potential changes to the instructions for medical use and/or the RMP. In addition, the RCH should classify opportunistic infections as an important identified risk.
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1Update of the sections “Special warnings and precautions for use” and “Adverse reactions” of the package insert. The risk assessment report and PRAC recommendations are forwarded to the CHMP for a decision.
Scientific conclusions of the EMA Committee for Medicinal Products for Human Use (CHMP) and justification for the need to amend the registration materials
Taking into account the PRAC report on the evaluation of PSURs for medicinal products containing enfortumab vedotin, the scientific conclusions of PRAC are as follows.
In view of the available data on leukopenia, fungal infections and urinary tract infections, obtained from clinical studies and spontaneous reports, which in some cases have a close temporal relationship, a positive reaction to withdrawal of the medicinal product (de-challenge) and a positive reaction to re-administration of the medicinal product (re-challenge) (regarding leukopenia), the PRAC considers that a causal relationship between the use of enfortumab vedotin and leukopenia, fungal infections and urinary tract infections is at least reasonably possible. The instructions for medical use of medicinal products containing enfortumab vedotin should be updated accordingly.
Having reviewed the PRAC recommendations, the CHMP agreed with the overall conclusions and grounds for the recommendations.
Based on the scientific conclusions on enfortumab vedotin, the CHMP considers that the benefit/risk balance of medicinal products containing enfortumab vedotin remains unchanged, subject to the proposed amendments to the instructions for medical use.
Comprehensive and up-to-date information on an individual medicinal product (summary of product characteristics, post-registration procedural steps, RMP summary, additional risk minimization measures, etc.) that is registered under the centralized procedure can be found in the Human medicines European public assessment report (EPAR) on the EMA website.
List of medicinal products containing enfortumab vedotin and authorized for medical use in Ukraine (according to the State Register of Medicinal Products as of 02.10.2026). (9.7 KB) (Downloaded: 12.10.2026 06:28:36)
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:
