Valproate and Fetal Anti-Convulsant Syndrome

A Backbench Business Committee debate, led by Norman Lamb on 19 October 2017 will focus on Fetal Anti-convulsant syndrome and sodium valproate. MPs and charities have raised concerns about the risks of fetal abnormalities and child developmental problems associated with the use of this drug in pregnancy, and women’s awareness of these risks.

There is a small risk of birth defects in any pregnancy. Generally, some anti-epileptic drugs (AEDs) may increase this risk, but there is also a risk from uncontrolled seizures in pregnancy. Medical organisations stress that women should not stop/alter their epilepsy medication without discussing this with their doctor.

Sodium Valproate is an anti-epileptic drug (AED) that is associated with greater risks in pregnancy than other AEDs (there are other valproate medicine, for example, valproic acid and valproate semisodium). The Medicines and Healthcare products Regulatory Agency (MHRA) report that whilst the general risk of a fetal abnormality is 2-3%, in women taking sodium valproate the risk is around 10%. Birth defects can include spina bifida, malformation of limbs and facial and skull malformations. It also states that the use of sodium valproate in pregnancy can affect a child’s development, about 30-40 children in 100 may have developmental problems such as delays in learning to walk and talk, lower intelligence than children of the same age and poor speech and language skills.

A concern raised by epilepsy charities and patient groups is that there has been a lack of information for women about the risks associated with sodium valproate. A 2016 survey of 2,788 women, showed that 20% of those who were taking sodium valproate for their epilepsy were not aware of the risks in pregnancy. This survey was repeated in 2017, when responses were very similar.

In 2016, the MHRA produced a valproate toolkit. This provides guidance for clinicians, and patient information on sodium valproate. This includes that:

• Women and girls of child bearing potential should not be prescribed valproate unless other treatments are ineffective or not tolerated;
• No one should stop taking valproate without discussing this with their doctor. The benefits and risks of the treatment need to be carefully balanced; and
• If valproate is the only option, women should be given effective contraception, and should have regular reviews of treatment.

There have been similar concerns about this drug internationally. In 2016, following a report that estimated that about 450 children in France had been affected by sodium valproate between 2006 and 2014, the French Parliament voted to establish a compensation fund for those affected. A class action legal case has also been recently launched against the company that manufacture the medicine in France, Sanofi. In the past there has also been legal action launched on this subject in the UK. In 2004, a class action was brought by a group of families under the Consumer Protection Act 1987 . The case was expected to go to trial in 2011, but the litigation was discontinued prior to this after the Legal Services Commission withdrew funding.

In March 2017, the European Medicines Agency launched a review of the safety of using valproate-containing medicines in women and girls who are pregnant or of childbearing age. This has included the first public hearing on a medicine safety review. The Pharmacovigilance and Risk Assessment Committee heard evidence from patients and patient representatives, healthcare professionals, academics and pharmaceutical industry representatives.

In Parliament, the Government have highlighted the MHRA’s work with a range of stakeholders to raise awareness of the risks of this medicine. They have said that there was no current plans to introduce a compensation fund similar to that in France, but there is support available through local authorities and CCGs for families with children born with a disability.

Epilepsy charities are calling on the Government to change the way prescribing is undertaken for sodium valproate. They suggest that repeat prescriptions should not be routinely renewed for this drug for longer than 12 months without a face to face consultation with a medical professional.