EMA’s safety committee (PRAC) has completed its review of Ixchiq, a live attenuated chikungunya vaccine, following reports of serious side effects.
The temporary restriction on vaccinating people aged 65 years and above, which was put in place during the review, will now be lifted.
However, PRAC concluded that, for people of all ages, the vaccine should only be given when there is a significant risk of chikungunya infection and after a careful consideration of the benefits and risks.
Serious side effects with the vaccine were reported mainly in people 65 years and older and in those with several underlying medical conditions. These side effects led to a worsening of the patients’ medical conditions or a deterioration in their general health, in some cases resulting in hospitalisation.
While most serious side effects occurred in older people, Ixchiq is effective at triggering the production of antibodies against the chikungunya virus which may be of particular benefit for older people who are at increased risk of severe chikungunya infection.
Healthcare professionals are reminded that Ixchiq must not be given to people whose immune system is weakened because of disease or medical treatment as they are at greater risk of having complications from vaccines containing live attenuated viruses.
The product information for Ixchiq will be updated with the latest recommendations following the review.
Ixchiq was authorised in the EU in June 2024. At the start of the PRAC review, around 36,000 doses of the vaccine had been used worldwide.
A direct healthcare professional communication (DHPC) will be sent to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC will also be published on a dedicated page on the EMA website.
More information is available in EMA’s public health communication.
Update to product information recommended to better describe the risk
PRAC has concluded its review of the known risk of encephalitis (inflammation of the brain) with the varicella (chickenpox) vaccines Varilrix and Varivax. The review was triggered by a case of encephalitis with fatal outcome after vaccination with Varilrix.
After carefully evaluating the available evidence from clinical trials, the scientific literature and post-marketing exposure, the committee has recommended an update to the product information of Varilrix and Varivax to further describe the severity of the risk of encephalitis. The two vaccines remain contraindicated in immunocompromised people and no additional risk minimisation measures are required.
Varicella vaccines are also authorised as part of measles, mumps, rubella, and varicella (MMRV) vaccines, namely Priorix Tetra and Proquad. PRAC considered that the product information of MMRV vaccines should also be updated in line with varicella vaccines.
The amended product information will give further detail on the known side effect encephalitis which has been observed with live attenuated varicella vaccines, including in a few cases with fatal outcome.
People who receive the vaccine should seek immediate medical attention if they develop signs of infection or inflammation of the brain.
Committee will review results of a recent study which does not replicate previous findings
PRAC is assessing new data from a recent study which used multiple databases in Denmark to investigate the potential risk of neurodevelopmental disorders (NDD) in children born to men treated with valproate, levetiracetam or lamotrigine before conception.
Valproate is a medicine used to treat epilepsy, bipolar disorders and in some countries for migraine.
Neurodevelopmental disorders are problems with development that begin in early childhood, such as autism spectrum disorders, intellectual disability, communication disorders, attention deficit/hyperactivity disorders and movement disorders.
In January 2024, the assessment of the findings of a post authorisation safety study (PASS) carried out by companies that market valproate, which used data from multiple registry databases in Denmark, Norway and Sweden, together with other available information, led the PRAC to recommend precautionary measures for the treatment of male patients with valproate medicines. At that time, while the committee acknowledged that the PASS data had limitations, PRAC concluded that NDD are a potential risk in children born to men treated with valproate during the three months before conception, and therefore information to patients and health care professionals were warranted.
The aim of this new study using Danish data sources was to replicate the results from the PASS. However, results from this new study did not suggest an association between valproate use by the father and an increased risk of NDD in the child.
PRAC has initiated a signal procedure to understand the difference in the findings across the studies and requested further information and analysis from the marketing authorisation holders for valproate.
EMA will communicate further when more information becomes available.
Clozapine: Revised recommendations for routine blood count monitoring
PRAC has endorsed a DHPC informing about revised recommendations for the monitoring of the blood count to minimise the risk of severe neutropenia and agranulocytosis with clozapine.
Clozapine is an atypical antipsychotic medicine indicated in treatment-resistant schizophrenia patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including other atypical antipsychotics. It is also used in psychotic disorders occurring during Parkinson's disease, in cases where standard treatment has failed.
Clozapine is known to increase the risk for neutropenia and agranulocytosis, and regular blood count monitoring is in place to minimise this risk. Neutropenia involves low levels of a type of white blood cells called neutrophils, which can leave patients vulnerable to infections. Agranulocytosis involves a sudden and sharp decrease of neutrophils, representing a very serious form of neutropenia.
New evidence from the scientific literature suggests that, although clozapine-induced neutropenia can occur at any time during treatment, it is predominantly observed during the first year, with the incidence peaking in the first 18 weeks of treatment. After this the incidence decreases becoming progressively lower after two years of treatment in patients without previous episode of neutropenia.
Therefore, PRAC recommended less frequent blood count monitoring. For example, in patients without neutropenia, the frequency of monitoring is reduced to every 12 weeks after one year, and to once a year after two years of treatment. Furthermore, monitoring is now recommended to be based solely on the count of absolute neutrophil count (ANC), a measure of the number of neutrophils. This aligns with current evidence that ANC is a more specific and clinically relevant marker for assessing the risk of neutropenia. Therefore, the requirement for monitoring white blood cell counts has been removed.
The product information for all clozapine-containing medicines will be updated to reflect the monitoring frequency for the risk of clozapine-related agranulocytosis and the revised ANC thresholds for treatment initiation and continuation.
The DHPC for clozapine will be disseminated to healthcare professionals by the marketing authorisation holders, according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registers in EU Member States.
