New measures introduced by EMA for men prescribed Epilim (Sodium Valproate).

Last Updated: Tue, 17/01/2024

Following an ongoing review of new data, the European Medicines agency’s Pharmacovigilance Risk Assessment Committee (PRAC) have announced new precautionary safety measures for the treatment of males with Epilim (sodium valproate).

Pharmacovigilance Risk Assessment Committee (PRAC)

The introduction of the new measures comes following a review by PRAC in 2023 of a retrospective observational study using data from registry databases in Denmark, Norway, and Sweden. The results of the study suggested there may be an increased risk of neurodevelopmental disorders (NDDs) in children born to men taking valproate in the 3 months before conception. It found a risk of 5.6% to 6.3% for children born to fathers treated with valproate, compared with 2.5% to 3.6% for children born to fathers treated with two other epilepsy drugs (lamotrigine or levetiracetam).

 In the study, around 5 children in 100 born to fathers treated with valproate around conception were diagnosed with a neurodevelopmental disorder. This is compared to 3 in 100 children whose fathers were taking lamotrigine or levetiracetam during the same period.

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.

While we understand that this may be worrying for men being treated with Sodium Valproate, as it was for women it is important to note that the PRAC have acknowledged that the study has limitations. These include:

  • Differences between the treatment groups and in follow-up times meant that it could not be established whether the increased occurrence of these disorders suggested by the study was due to valproate use.
  • The study was not large enough to identify which types of neurodevelopmental disorders children could be at increased risk of developing.

In addition, the full study has not yet been published. From our contributions to a stakeholder meeting on this matter towards the end of 2023, we understand that the EMA do plan to publish the full study in the coming months.

New precautionary measures for valproate use in men.

The new precautionary measures which are to be introduced are as follows:

  • It is recommended that in male patients, valproate is initiated and supervised by a specialist experienced in treatment of epilepsy or bipolar disorder.
  • Prescribers should inform male patients about the potential risk and discuss with them the need to consider effective contraception, including for a female partner, while using valproate and for 3 months after stopping the treatment.
  • Treatment with valproate in male patients should be regularly reviewed by prescribers to evaluate whether valproate remains the most suitable treatment for the patient. For male patients planning to conceive a child, suitable alternative treatment options should be considered and discussed with the patient. Individual circumstances should be evaluated for each patient. It is recommended that advice from a specialist experienced in the management of epilepsy or bipolar should be sought as appropriate.
  • Male patients should be advised to not donate sperm during treatment and for at least 3 months after treatment discontinuation.

As part of the measures above, updates will be made to the patient information materials associated with Sodium Valproate. These include:                                                                                                                        

  • Update to existing guide to healthcare professionals, to include dedicated section on use in male patients.
  • Introduction of a new patient guide for men as well as inclusion of information in the existing patient card.
  • Product information will be updated (on the package insert) to include details of the study results and its limitations, as well as the new precautionary measures.

The introduction of these measures in Ireland will be the responsibility of the Health Products Regulatory Authority (HPRA), we look forward to working with the HPRA and shall be in close contact with the over the coming weeks and months on the introduction of these measures. We will supply further updates on our website and social media channels as soon as we have them.

You can read PRAC’s announcement of these precautionary measures by visiting the ‘European Medicines Agency’ website.

We know that this latest information may be worrying for men with epilepsy and other conditions who are planning to start a family and has already had a family while on Epilim (sodium valproate) but please DO NOT STOP taking your medication without first discussing this with your medical team. Discontinuing or reducing your anti-seizure medications is likely to lead to the recurrence of seizures or an increase in seizure frequency.

Some of this information may be confusing considering other regulatory bodies went one step further. We believe you don’t have to reinvent the wheel you just need to ensure that the one that’s in place works for both men and women.

OACS Ireland: If you feel your child/children have been harmed by to Epilim (Sodium Valproate) please contact OACS Ireland by Emailing: info.oacsireland@gmail.com  Or have a friendly chat with us by phone our contact details are as follows Mobile: 089 219 6011. We look forward to hearing from you.

Epilepsy Ireland: You can also contact your Epilepsy Ireland Community Resource Officer for assistance or support on your journey with epilepsy. You can find their details by visiting the ‘Our Local Service’ section of our website.  

Refs.

  1. DHPC, 2. Drug Safety Newsletter, 3. Valproate (Epilim-) – EMA review of study in children whose fathers where treated with valproate (hpra.ie)
  2. May 2023: Update on risks associated with paternal exposure to Sodium Valproate (Epilim). https://rb.gy/2luxe
  3. August 2023: August EMA study suggests possible increased risk to children of fathers treated with (Epilim) Sodium Valproate. http://tinyurl.com/2wjykfdj
  4. October 2023  DHCP The DHCP which has been issued on this ongoing review can be read and downloaded at the end of this article
  5. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published new guidance on medicines containing valproate