Depakine® scandal: a practical sheet for pharmacists

Already prosecuted for “Aggravated deception” and “involuntary injuries”, the laboratory SANOFI France has just been indicted for “involuntary homicides” in the case of Dépakine, an antiepileptic whose risks of congenital malformations in particular have been known for a long time . “The judge decided to place Sanofi under judicial control. He indeed considered that the link between Dépakine and the damage caused to the fetuses was scientifically established, but also that Sanofi had caused damage of exceptional gravity”, explains the president of the Aid to parents of children suffering from Anti-Convulsant Syndrome (APESAC) in a press release, congratulating the victims for having responded to the association’s call to file a complaint so that “these crimes do not go unpunished”.

The question now is whether or not the lab can be held responsible for the deaths of four babies in 1990, 1996, 2011 and 2014, according to The world. In a statement to AFP, Sanofi disputes the lawsuits and believes “have complied with their information obligations” and informs that he has seized the investigative chamber in order to contest his indictment because “all of these elements do not in any way prejudge the responsibility of the laboratory”.

On July 2, 2020, the administrative court of Montreuil (Seine-Saint-Denis) had for the first time recognized the responsibility of the State in the Depakine® scandal. In a communicated, he explained that the state “failed in its control obligations by not taking appropriate measures and incurred its responsibility“. He was ordered to compensate three families.”whose children are severely disabled after being exposed in utero to this antiepileptic“, reports AFP. The court nevertheless specified that”responsibilities were shared, to a lesser extent, by the Sanofi laboratory and prescribing physicians“. Each family will receive between 20,000 and 200,000 euros,”depending on the date of birth of the five children concerned, now aged 11 to 35“.

124 children born in 2018 exposed in utero

At the beginning of February, the pharmaceutical group Sanofi was indicted for “aggravated deception” and “unintentional injuries”In the Depakine® case. A few days later, as part of monitoring exposure to drugs containing valproate or a derivative (Depakine®, Depakine Chrono 500®, Micropakine®, and generics, Depakote®, Depamide®), the National Safety Agency of the drug (ANSM) has published data for the period from 2013 to 2019: if this exposure has sharply decreased in pregnant women and women of childbearing age thanks to the restriction measures put in place since 2015, efforts must be continued.

The ANSM reveals that during this period, the number of children born from pregnancies exposed to valproate decreased by 82%. On the other hand, 124 children born in 2018 would have been exposed in utero to valproate, “including 92 from mothers with epilepsy and 32 from mothers with bipolar disorder [autre indication du valproate, NDLR]”.

In women of childbearing age, exposure was reduced by 55%. “This decrease related to both initiations (-69%) and renewals of treatment (-53%)”, Specifies the ANSM.

Additional analyzes in progress

The agency claims that “additional analyzes are underway in order to characterize in more detail the prescribing context in these pregnant women and to study the benefit of implementing targeted measures with prescribers”. Indeed, if valproate and its derivatives are contraindicated during pregnancy, they can be prescribed during this period in the treatment of epilepsy if and only if it does not exist “appropriate therapeutic alternative”. In women of childbearing age, they are used “if no other treatment is possible and all the conditions of the pregnancy prevention program are met (in particular: use of at least one method of contraception, signature of a care agreement)”.

The ANSM also adds that during the period studied, “an increasing proportion of exposed pregnancies have been terminated”, Voluntarily or medically.

Strengthening of exposure reduction measures

She concludes by explaining that measures to reduce exposure to valproate are “maintained”And will be“soon to be reinforced, via the integration of the patient card inside or on the outside of the medicine box, the affixing of a QR code on these boxes and on the leaflets leading to a dedicated information page on the ANSM website”.

A page put online by the ANSM to inform about the risks for pregnancy

The National Agency for the Safety of Medicines and Health Products (ANSM) has put online an information page for pregnant women, explaining the risks for their pregnancy.

“This page provides access to information presented according to the pathology for which these drugs have been prescribed (epilepsy or manic episodes of bipolar disorder) and whether the patients are of childbearing age, or whether they wish to become pregnant. or that they are pregnant“, explains the ANSM in a press release.”Practical advice is then offered depending on the situation that concerns them.“.

The ANSM also specifies that by the end of the year, a QR code referring to this page will be printed on the boxes of drugs concerned as part of the European program for the prevention of pregnancies in women exposed to valproate.

Sodium valproate and derivatives: a practical sheet for pharmacists

ANSM has provided pharmacists with a practical sheet recalling “the points that the pharmacist must check and the actions that he must put in place in order to ensure an adequate dispensing of drugs based on sodium valproate or its derivatives in girls and women of childbearing age “, can we read on the ANSM website.

This sheet lists the key steps to follow:

• First step: verification of mandatory documents presented by the patient namely the specialist’s prescription less than a year old, the renewal order if necessary as well as the annual care agreement form, completed and signed by the woman;
• Second step: the documents to submit to the patient to know his patient card (with his name and the date of dispensation) by checking that it includes the content. The pharmacist must ask the patient to keep this document and give her the patient information brochure ;
• Third step: the advice and information to remember namely the need to have a method effective contraception during the entire treatment as well as carrying out pregnancy tests at regular intervals. If the woman has a suspicion of pregnancy, she must go urgently to her specialist doctor. If she has a desire for pregnancy, she should also consult quickly. Also important reminder, do not stop treatment suddenly but talk to his doctor.