Potential risk of neurodevelopmental disorders in children born to men treated with valproate medicines: PRAC recommends precautionary measures
EMA’s Safety Committee (PRAC) is recommending precautionary measures for the treatment of male patients with valproate medicines to address a potential increased risk of neurodevelopmental disorders in children born to men treated with valproate during the 3 months before conception, following a review of data from a retrospective observational study carried out by companies that market valproate as an obligation following a previous review of valproate use during pregnanc and other sources of information (non-clinical studies, scientific literature, consultation of patients and clinical experts).
The PRAC latest recommendations come in addition to restrictions and other measures already in place to avoid exposure to valproate during pregnancy, approved following a referral procedure for valproate and related substances in 2018.

New safety information for healthcare professionals: new precautionary measures for medicines containing valproate
The PRAC also discussed a Direct Healthcare Professional Communication (DHPC) for valproate medicines which will inform healthcare professionals about the potential risk of neurodevelopmental disorders in children of fathers treated with valproate in the 3 months before conception and recommend that the treatment is started, supervised and reviewed regularly by a specialist in the management of epilepsy, bipolar disorder or migraine, particularly when the patient is planning to conceive a child.
Once adopted by the CMDh, the DHPC will be disseminated to healthcare professionals by the marketing authorization holder, according to an agreed communication plan and published on the Direct healthcare professional communications page and in national registers in EU Member States.

Launch of safety review of CAR T cell medicines
The PRAC started a signal procedure to review data on T-cell-related malignancies, including T-cell lymphoma and leukaemia, for the six approved T-cell-based chimeric antigen receptor (CAR) medicines, which belong to type of personalized cancer immunotherapies where patients' white blood cells (a particular type, called T cells), are reprogrammed and re-injected to attack the cancer. These medicines are used to treat relapsed or refractory blood cancers such as B-cell leukaemia, B-cell lymphoma, follicular lymphoma, multiple myeloma, and mantle cell lymphoma.
A secondary malignancy is when a patient who has cancer (current or previous) develops a second cancer that is different from the first cancer. Malignancies of T cell origin are cancers that begin in T cells. For all six CAR-T cell products, secondary malignancies were considered as an important potential risk at the time of their authorization and included in the Risk Management Plans (RMP), according to which Close monitoring is already in place and the marketing authorisation holders of the approved medicines are required to regularly submit interim results from the imposed long-term safety and efficacy studies.
The PRAC is now reviewing all available evidence, including information on 23 cases of various types of T-cell lymphoma or leukaemia in EudraVigilance, the EU database of adverse drug reactions to medicine and will decide whether on the need for any regulatory action.