This document communicates important safety updates for three different categories of products, focusing on new aspects of known risks.
1. CAR T-cell Therapies (Ciltacabtagene autoleucel, Idecabtagene vicleucel, Tisagenlecleucel)
Safety Signal: Progressive multifocal leukoencephalopathy (PML) (EPITT no 20153)
Updates:
- Product: Kymriah, Abecma, Carvykti
- Change: A new warning has been added to the SmPC Section 4.4 (Special Warnings).
- Details: The warning states that reactivation of the John Cunningham (JC) virus, leading to the rare and often fatal brain infection PML, has been reported in patients treated with these CAR-T cell therapies. This risk is noted particularly in patients who had received prior treatment with other immunosuppressive medications. Fatal outcomes have been reported for Kymriah and Carvykti.
2. Clozapine
Safety Signal: New aspect of the known risk of neutropenia/agranulocytosis (EPITT no 20141)
Updates:
This is a major update to the risk minimization measures for Clozapine, a drug known to cause agranulocytosis (a severe drop in white blood cells). The changes provide more detailed and nuanced monitoring schedules.
- Key Changes in the SmPC:
- Monitoring Frequency: The schedule for Absolute Neutrophil Count (ANC) monitoring is now more flexible based on treatment duration and patient history:
- After 12 months with no neutropenia, monitoring can be reduced to every 12 weeks.
- After 24 months with no neutropenia, monitoring can be reduced to once a year.
- Benign Ethnic Neutropenia (BEN): Specific ANC thresholds and actions are provided for patients with confirmed BEN, allowing for lower ANC thresholds for starting and continuing treatment.
- Treatment Interruption: Clear guidelines are provided for resuming monitoring after treatment is interrupted for non-haematological reasons, depending on the duration of the interruption and the patient’s treatment history.
- Interaction with Valproic Acid: A specific warning is added that concomitant use with valproic acid may increase the risk of neutropenia, requiring careful monitoring.
- Monitoring Frequency: The schedule for Absolute Neutrophil Count (ANC) monitoring is now more flexible based on treatment duration and patient history:
- Package Leaflet: Updated to reflect the new, more flexible monitoring schedule for patients.
3. Live Vaccines (Varicella and MMRV)
Safety Signal: New aspect of the known risk of encephalitis (EPITT no 20180)
Updates:
- Products: Varlirix, Varivax, Priorix Tetra, ProQuad (Varicella and MMRV vaccines).
- Change: Enhanced warnings about the risk of encephalitis (brain inflammation) have been added to the SmPC and Package Leaflet.
- Details:
- The SmPC now explicitly states that encephalitis has been reported during post-marketing use, with fatal outcomes in a few cases, especially in immunocompromised patients.
- It instructs healthcare professionals to advise vaccinees/parents to seek prompt medical attention for symptoms suggestive of encephalitis (e.g., reduced consciousness, convulsions, ataxia with fever and headache).
- The Package Leaflet for patients/parents has been updated with a clear, prominent warning about this risk, describing the symptoms and emphasizing the need for immediate medical care.
Purpose
These updates strengthen the existing safety information for these products. They provide healthcare professionals and patients with more precise monitoring guidelines (for Clozapine) and enhance the awareness of rare but serious risks (PML with CAR-T therapies and encephalitis with live vaccines), enabling earlier detection and management.
