New Restrictions on The Use of Epilepsy Drug Epilim in Pregnancy

I wrote a blog last year on 24 October about the harm that Sodium Valproate, a controversial drug used to treat epilepsy, can have on unborn babies if used by mothers during pregnancy.

The drug made headlines in 2017 when it was revealed that drug regulators knew of the drug's problems as far back as the 1970s but did not to include this on patient information leaflets for fear it “could give rise to fruitless anxiety”.

Over the years however there have been numerous attempts to improve the communication of the risks of taking valproate medication during pregnancy to women, and in particular to their unborn child, although recent studies suggest that some women are still unaware of these risks.


Developments over the years

In 2004 The National Institute for Health and Care Excellence (NICE) guidelines on the diagnosis and management of epilepsy were amended. They stated that women and girls of childbearing potential (including young girls likely to need treatment into their childbearing years) and their parents and/or carers if appropriate, should be informed of the risk of anti-epileptic drugs (AED) causing malformations and possible neural developmental impairments in an unborn child, and assess the risk and benefits of treatment with individual drugs.

A study by Bromley et al in 2010 revealed that children exposed to sodium valproate had a statistically significant increased risk of delayed early development, compared to the control group of children. Also in 2010 an article published by Hill et al titled “Teratogenic effects of antiepileptic drugs” noted that foetal malformation linked with sodium valproate was known to be dose related.

In 2012 the NICE guidelines, referred to above, were again updated. Much of the 2004 update remained the same but newly added was that doctors seeking to prescribe sodium valproate should specifically discuss the risk of its continued use to any unborn child, being aware that higher doses of sodium valproate (more than 800 mgs per day) is associated with a greater risk. It also added that doctors needed to be aware of the latest data on the risk to the unborn child associated with AED therapy when prescribing for women and girls of present and future childbearing potential.

In November 2014, the European Medicines Agency’s (EMA) Pharmacovigilance and Risks Assessment Committee (PRAC) conducted a review of the valproate drug and agreed to strengthen warnings and restrictions on the drug’s use in pregnancy, due to the risk of malformations and developmental problems.

After warnings were strengthened in 2014, in 2015 the Medicines and Healthcare Regulatory Agency (MHRA) advised healthcare professionals against prescribing valproate-containing medicines in women and girls of/or nearing childbearing potential unless other treatments were ineffective or not tolerated.

Two years later the MHRA released further resources including a toolkit to help healthcare professionals talk to women with epilepsy about sodium valproate's risks during pregnancy. New safety warnings were also introduced which included written warnings on the drug's packaging.

On April 6 2017, NHS Improvement and the MHRA sent a patient safety alert through the central NHS system to further highlight sodium valproate's risks during pregnancy and published their Drug Safety Update which advised healthcare professionals not to prescribe sodium valproate to females unless other treatments were ineffective or poorly tolerated. Doctors also had to ensure that women and girls taking valproate medications understood the 10% risk of birth defects and the 30–40% risk of neurodevelopmental disorders. It also stated that valproate used in women and girls of childbearing age must be initiated and supervised by specialists in the treatment of epilepsy.

Despite these previous recommendations, women were still not always receiving the right information in a timely manner and my previous blog discussed the public hearing that was held in London on 26 September 2017 by the PRAC as part of a safety review of the drug, where EU citizens spoke of their experiences of Epilim. Nearly eight months on, there have been further developments that have put sodium valproate back in the headlines.

New developments

Sodium valproate must no longer be prescribed to girls and women of childbearing age in the UK unless they have a Pregnancy Prevention Programme (PPP) in place, under new rules brought in by the MHRA. The PPP requires women to complete a signed risk acknowledgement form when their treatment is reviewed by a specialist, which must take place at least annually.

This programme will also be supported by smaller pack sizes to encourage monthly prescribing of the medication, as well as a pictogram/warning image on labelling, similar to the warnings on cigarette packaging.

All women and girls who are currently prescribed valproate are advised to contact their GP and arrange to have their treatment reviewed. Doctors will need to weigh up with their patients the benefits and risks in any change to their epilepsy medication or a reduced dosage. Women should be adequately informed of risks and benefits of available treatment in their circumstances to enable them to be in a position to choose the risk they are willing to accept. They should not stop taking valproate without medical advice.