PRAC Recommendations on Safety Signals

Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands An agency of the European Union Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 © European Medicines Agency, 2025. Reproduction is authorised provided the source is acknowledged. 24 November 2025 Pharmacovigilance Risk Assessment Committee (PRAC) Adopted at the 27-30 October 2025 PRAC meeting This document provides an overview of the recommendations adopted by the Pharmacovigilance Risk Assessment Committee (PRAC) on the signals discussed during the meeting of 27-30 October 2025 (including the signal European Pharmacovigilance Issues Tracking Tool [EPITT] reference numbers). PRAC recommendations to provide supplementary information are directly actionable by the concerned marketing authorisation holders (MAHs). PRAC recommendations for regulatory action (e.g. amendment of the product information) are submitted to the Committee for Medicinal Products for Human Use (CHMP) for endorsement when the signal concerns Centrally Authorised Products (CAPs), and to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) for information in the case of Nationally Authorised Products (NAPs). Thereafter, MAHs are expected to take action according to the PRAC recommendations. When appropriate, the PRAC may also recommend the conduct of additional analyses by the Agency or Member States. MAHs are reminded that in line with Article 16(3) of Regulation No (EU) 726/2004 and Article 23(3) of Directive 2001/83/EC, they shall ensure that their product information is kept up to date with the current scientific knowledge including the conclusions of the assessment and recommendations published on the European Medicines Agency (EMA) website (currently acting as the EU medicines webportal). For CAPs, at the time of publication, PRAC recommendations for update of product information have been agreed by the CHMP at their plenary meeting (10-13 November 2025) and corresponding variations will be assessed by the CHMP. For nationally authorised medicinal products, it is the responsibility of the National Competent Authorities (NCAs) of the Member States to oversee that PRAC recommendations on signals are adhered to. Variations for CAPs are handled according to established EMA procedures. MAHs are referred to the available guidance. Variations for NAPs (including via mutual recognition and decentralised procedures) are handled at national level in accordance with the provisions of the Member States. Expected publication date. The actual publication date can be checked on the webpage dedicated to PRAC recommendations on safety signals. The relevant EPITT reference number should be used in any communication related to a signal.

Page 2/6 The timeline recommended by PRAC for submission of variations following signal assessment is applicable to both innovator and generic medicinal products, unless otherwise specified. For procedural aspects related to the handling of PRAC recommendations on signals (e.g. submission requirements, contact points, etc.) please refer to the Questions and Answers on signal management.

Page 3/6 1. Recommendations for update of the product information 1.1. Bosutinib – Cutaneous vasculitis Authorisation procedure Centralised and non-centralised EPITT No 20184 PRAC Rapporteur Martin Huber (DE) Date of adoption 30 October 2025 Recommendation Having considered the available evidence in EudraVigilance, literature and the responses of the Marketing Authorisation Holder (MAH), the PRAC has agreed that the MAHs of bosutinib containing products should submit a variation within 2 months from the publication of the PRAC recommendation, to amend the product information as described below (new text underlined): Under SOC Skin and subcutaneous tissue disorders with frequency “Uncommon”: Cutaneous vasculitis Uncommon (may affect up to 1 in 100 people): Inflammation of blood vessels in the skin which may result in a rash or bruising (cutaneous vasculitis). 1.2. Datopotamab deruxtecan – Anaphylactic reaction Authorisation procedure Centralised EPITT No 20181 PRAC Rapporteur Mari Thörn (SE) Date of adoption 30 October 2025 Recommendation Having considered the available evidence in EudraVigilance including the cumulative review submitted by the Marketing Authorisation Holder (MAH), the PRAC has agreed that the MAH of Datroway (DAIICHI SANKYO EUROPE GMBH) should submit a variation within 2 months from the publication of the PRAC recommendation, to amend the product information as described below (new text underlined): Translations in all official EU languages of the new product information adopted by PRAC are also available to MAHs on the EMA website.

Page 4/6 4.4 Special warnings and precautions for use Hypersensitivity Serious, anaphylactic reactions have been observed with datopotamab deruxtecan. Patients should be observed closely for hypersensitivity/allergic reactions, which may have the same clinical presentation as an infusion-related reaction. Medicinal products to treat such reactions, as well as emergency equipment, should be available for immediate use. In the event of a serious hypersensitivity reaction, datopotamab deruxtecan treatment must be immediately and permanently discontinued. Tabulated list of adverse reactions Table 3 System organ class Frequency category Adverse reactions Immune system disorders Not known Anaphylactic reaction 2. What you need to know before you are given Datroway Warnings and precautions Datroway may also cause: • allergic reactions, including anaphylaxis: allergic reactions which can be serious can occur during or shortly after the infusion. Your doctor will observe you closely while you are being given Datroway. For signs and symptoms of allergic reactions see section 4. Possible side effects. If you experience a serious allergic reaction your doctor will permanently stop your treatment. […] Some side effects may be serious, and possibly fatal. Speak with your doctor or nurse immediately if you notice any of the following: […] Not known (frequency cannot be estimated from the available data) • Allergic reaction, including anaphylaxis: may include signs and symptoms such as rash, severe itching, flushing, dizziness, swelling of the face, lips, tongue and/or throat (angioedema), difficulty breathing or swallowing, and/or low blood pressure. Getting medical treatment right away may help keep these problems from becoming more serious.

Page 5/6 1.3. Epcoritamab – Hypogammaglobulinaemia Authorisation procedure Centralised EPITT No 20174 PRAC Rapporteur Maria Martínez González (ES) Date of adoption 30 October 2025 Recommendation Having considered the available evidence in EudraVigilance, literature and the responses of the Marketing Authorisation Holder (MAH), the PRAC has agreed that the MAH of Tepkinly, AbbVie Deutschland GmbH & Co. KG, should submit a variation within 2 months from the publication of the PRAC recommendation, to amend the product information as described below (new text underlined): 4.4 Special warnings and precautions for use Serious infections […] In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines. Hypogammaglobulinaemia has also been reported in patients receiving epcoritamab (see section 4.8). Immunoglobulin (Ig) levels should be monitored prior to and during treatment. Patients should be treated according to local institutional guidelines, including infection precautions and antimicrobial prophylaxis. […] Table 7, under SOC Immune system disorders with frequency “Very common” for all grades and “Uncommon” for grades 3-4: Hypogammaglobulinaemia 2. What you need to know before you use Tepkinly Warnings and precautions […] If any of the above apply to you (or you are not sure), talk to your doctor or nurse before you are given Tepkinly. Your doctor or nurse will do blood tests, prior and during your treatment with epcoritamab, to check your antibody levels, which may indicate your risk of infection and the need for specific treatment. Tell your doctor straight away if you get symptoms of any of the side effects listed below, during or after treatment with Tepkinly. You may need additional medical treatment. […]

Page 6/6 Other side effects […] Very common: may affect more than 1 in 10 people […] Shown in blood tests […] • low levels of immunoglobulins, which may lead to infections 2. Recommendations for submission of supplementary information INN Signal (EPITT No) PRAC Rapporteur Action for MAH MAH Nemolizumab Erythema multiforme (20207) Liana Martirosyan (NL) Assess in the next PSUR (submission by 6 December 2025) Galderma International Selumetinib Photosensitivity reaction (20208) Mari Thörn (SE) Assess in the next PSUR (submission by 18 December 2025) AstraZeneca AB 3. Other recommendations INN Signal (EPITT No) PRAC Rapporteur Action for MAH MAH Adalimumab Morphoea (20166) Karin Bolin (SE) Monitor in PSUR MAHs of adalimumab containing products with an obligation to submit PSURs Sulfasalazine Idiopathic intracranial hypertension (pseudotumor cerebri) (20188) Marie Louise Schougaard Christiansen (DK) Monitor in PSUR MAHs of sulfasalazine containing products with an obligation to submit PSURs