Reduce the number of high-risk pregnancies by better informing mothers and doctors: the National Agency for the Safety of Medicines and Health Products (ANSM) unveils on Wednesday November 29 a new overview of the risks linked to the consumption of antiepileptics.
“Four years after a first report, the panorama of antiepileptic drugs and the risks for the fetus has been modified by new data since 2019. New risks, previously suspected or unknown, are identified for drugs, which sometimes had other risks known,” explains Philippe Vella, medical director of the ANSM, to AFP.
The objective is to classify antiepileptic drugs according to the level of risk for the fetus, and to best inform prescribing doctors and patients. Valproate (Depakine and generics, Micropakine, Depakote and its generic Divalcote, Depamide) remains “the most at risk” if taken during pregnancy. This antiepileptic drug “leads to the most malformations in children, with a risk multiplied by 4 to 5 (11%) compared to the risk without treatment”, and “carries a high risk of neurodevelopmental disorders (30 to 40% of children exposed in utero),” detailed the agency.
And, from now on, its intake by the father, in the three months before conception, is also suspected of being a neurodevelopmental risk for the fetus, recalls the ANSM. While awaiting the conclusions of a European evaluation, it has already informed doctors and patients. One of the major changes made by the medicines agency concerns topiramate, sold under the brand Epitomax by the Janssen laboratory but also as a generic by other manufacturers and a source of growing concern for more than a year.
If the risk of major malformations (hare lip, poor placement of the urethra on the penis, very low birth weight, etc.) was "known" for this medication, the risk of neurodevelopmental disorders is "confirmed", according to the report. This risk is increased by two to three times compared to children born to epileptic mothers without treatment.
According to a study, carried out using the health data of several million Scandinavian women and published at the end of May 2022, the risk of intellectual disability is more than tripled in children whose mother took topiramate during pregnancy and the risk of disorders autism multiplied almost threefold.
In its wake, the ANSM asked its European counterpart, the European Medicines Agency (EMA), to reassess the conditions for prescribing topiramate and, among other things, called for this antiepileptic drug to be used only in pregnant women. “in case of absolute necessity”. Another change in the panorama drawn up by the ANSM: pregabalin (Lyrica and generics) presents a “confirmed” risk of major malformation in children - multiplied by almost 1.5 -, only “suspected” in 2019.
With carbamazepine (Tegretol and generics), whose risk of major malformation was “known” (multiplied by 2 to 3), there is also “a possible increase” in the risk of neurodevelopmental disorders. Of the twenty antiepileptic drugs reviewed, the risks of other treatments are not changed compared to 2019, at this stage of knowledge.
In recent years, the ANSM has tightened its policy towards antiepileptic drugs deemed to pose a risk during pregnancy. The involvement of several of these drugs in fetal disorders has been proven, notably for sodium valproate, or Depakine from Sanofi, at the heart of a scandal fueling several legal proceedings.
But in some women, only these treatments prove effective against epilepsy. It is therefore up to doctors alone to assess whether the risks represented by the attacks are high enough to compensate for those that the treatment poses to the unborn child.
The ANSM, however, provides patients with an information sheet summarizing the known risks of antiepileptic drugs for the future child and giving various advice, in particular on methods of contraception to adapt - certain antiepileptic drugs can reduce the effectiveness of the pill.