2023-11-29 13:35:54

Following the new available data, we have initiated several actions at national and European level to secure the use of antiepileptics. We are continuing to monitor the risks associated with the exposure of pregnant women to these medications.

What to learn from this report?

This update confirms the already known level of risk of valproate, whether the risk of malformation or that of neurodevelopmental disorders if taken by the mother during pregnancy.
The risk of major malformation associated with taking pregabalin is confirmed.
An increased risk of neurodevelopmental disorders is identified for topiramate and possible for carbamazepine.

Valproate (and its derivatives valpromide, divalproate), this antiepileptic drug remains the most at risk if taken by the mother during pregnancy.

If taken by the mother during pregnancy, valproate causes the most malformations in the child, with a risk multiplied by 4 to 5 (11%) compared to the risk without treatment. It also carries a high risk of neurodevelopmental disorders (30 to 40% of children exposed in utero).

We remind you that valproate and its derivatives are strictly contraindicated during pregnancy in the management of bipolar disorders and should not be used in pregnant women with epilepsy, except in the absence of a therapeutic alternative.
Numerous pieces of information are available to patients and healthcare professionals.

Furthermore, a potential risk of neurodevelopmental disorders associated with taking valproate by the father in the three months preceding conception is currently being evaluated at European level. Pending the conclusions of this evaluation, we have sent an information letter to all healthcare professionals concerned to alert them to this potential risk. A patient information sheet was also designed to be given to patients.

The medicines concerned are: Depakine and generics, Micropakine, Depakote and its generic Divalcote and Depamide.

Topiramate, a confirmed risk of neurodevelopmental disorders

The risk of neurodevelopmental disorders in children exposed to topiramate during pregnancy is increased by 2 to 3 times (autism spectrum disorders up to 6% and risk of occurrence of intellectual disability up to 8% 1) by compared to children born to epileptic women who are not taking antiepileptic medications.

The risk of major malformations, multiplied by 3 compared to the risk without treatment, was already known.

In view of these new data, with the aim of reducing the risk of pregnancy occurring under topiramate, we have reserved its prescription for neurologists and pediatricians and requested the signing of an annual care agreement by the patient and her doctor whose presentation to the pharmacist determines the dispensing of the medication.
A European evaluation initiated at our request restricted the use of this drug in the case of women of childbearing age as we had proposed.

The drugs concerned are: Epitomax and generics.

1 These values ​​must be considered with caution given the limits of extrapolating these Scandinavian results to French data

Carbamazepine, a possible increase in the risk of neurodevelopmental disorders

According to new available data, it is possible that the risk of neurodevelopmental disorders is increased in children exposed to carbamazepine compared to the unexposed population.

The risk of major congenital malformations from carbamazepine is already known (2 to 3 times higher than that of the general population).

In order to ensure that patients are properly informed and reduce the still too high number of pregnancies under carbamazepine, we will make it compulsory in 2024 to sign a certificate of information shared by the patient and the prescribing doctor, the presentation of which to the pharmacist will determine the dispensing of the medication.

The drugs concerned are: Tegretol and generics

Pregabalin, malformation risk is confirmed

The new available data confirm the risk of major malformation in children, linked to exposure to pregabalin during pregnancy: it is multiplied by almost 1.5 compared to the population which has not been exposed to this medicine. This risk was only suspected in the 2019 report.

The drugs concerned are: Lyrica and generics.

Oxcarbazepine, a presumed increase in malformation risk / to be investigated?

Monitoring continues. Additional studies are necessary before being able to conclude whether or not there is a risk of malformation.

The drugs concerned are: Trileptal and generics.

The update of the available data has not modified the conclusions published in 2019 for other antiepileptic drugs.

For lamotrigine (Lamictal and generics) and levetiracetam (Keppra and generics, Leptax and Leviden), the available data do not demonstrate an increased risk of major congenital malformations or neurodevelopmental disorders.

Concerning vigabatrin (Kigabeq and Sabril), felbamate (Taloxa), zonisamide (Zonegran and generics) and gabapentin (Neurontin and generics), the available data are insufficient to conclude that there is an increased risk of major congenital malformations or disorders. neurodevelopmental.

Concerning (fos)phenytoin (Prodilantin, Di-Hydan and Dilantin), phenobarbital (Gardenal) and primidone (Mysoline), exposure to these molecules carries a risk of major congenital malformations; regarding the risk of neurodevelopmental disorders, the data remain insufficient to conclude.

Finally, for several other drugs, there is, to date, no data to conclude on the malformation risks and the risks of neurodevelopmental disorders: brivaracetam (Briviact); cannabidiol (Epidyolex); cenobamate (Ontozry); eslicarbazepine (Zebinix); ethosuximide (Zarontin); fenfluramine (Fintepla); lacosamide (Vimpat and generics); perampanel (Fycompa); rufinamide (Inovelon) and tiagabine (Gabitril).

As a reminder, the absence of data does not mean absence of risk but that the information is not known to date.

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