The UK licence and guidance relating to sodium valproate have been changed in the wake of the recent announcement of new Europe-wide safety measures relating to the drug.
The Medicines and Healthcare products Regulatory Agency has today revealed that it has changed the licence for valproate, which is marketed as Epilim and Depakote, as well as generic brands.
“It has taken many years to achieve these simple, straightforward and inexpensive healthcare improvements”
As a result, valproate must no longer be prescribed to women or girls of childbearing potential unless they are on a pregnancy prevention programme.
The move follows regulatory changes agreed in March by the European medicines regulatory body the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human.
It is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant while taking the drug which is linked to birth defects.
The measures follow years of campaigning for stronger action by charity’s and several attempts by regulators to beef up guidance and warnings since 1974 about the potential risks linked to the drug.
- New toolkit on risks of valproate during pregnancy
- Reminder on valproate risk for pregnant women
- Nurse-led project helps women with epilepsy plan pregnancy
Children born to women who take valproate during pregnancy are at significant risk of birth defects and persistent developmental disorders, noted the MHRA.
It highlighted that if valproate was taken during pregnancy, up to four in 10 babies were at risk of developmental disorders, and approximately one in 10 were at risk of birth defects.
Under the new MHRA rules, healthcare professionals who seek to prescribe valproate to their female patients must make sure they are enrolled in the pregnancy prevention programme.
“We are committed to making sure women and girls are aware of the very real risks”
This includes the completion of a signed risk acknowledgement form when their treatment is reviewed by a specialist, at least annually.
In addition, all women and girls prescribed valproate have been advised to contact their general practice to arrange for a treatment review.
The body said today’s regulatory changes would be further supported in the upcoming months by smaller pack sizes to encourage monthly prescribing and a warning image on valproate labelling.
The MHRA measures are also being supported across the NHS with other changes, such as new GP system computer alerts, to make sure “changes in prescribing behaviour take place promptly”.
For example, NHS Digital has worked with GP systems suppliers to provide a search and audit function to identify women and girls on valproate, as well as updating valproate prescribing alerts.
A letter will be sent to all relevant healthcare professionals in the coming weeks outlining the new requirements and providing updated educational materials.
“We have been working closely with the MHRA and GP system suppliers to ensure clinicians in primary care are informed”
In parallel, the National Institute for Health and Care Excellence is amending its guidelines where valproate is mentioned, to reflect the new regulatory position.
NICE has also begun work on a full update of its epilepsy guideline, which will specifically focus on areas where valproate is currently regarded as the drug of choice but conflicts with the new position.
Dr June Raine, director of MHRA’s Vigilance and Risk Management of Medicines Division, said: “We are committed to making sure women and girls are aware of the very real risks of taking valproate during pregnancy.
“This regulatory position has been developed through close collaboration with professional bodies, health system organisations, and patient and campaign groups,” she said.
Health minister Lord O’Shaughnessy added: “The focus will now be on explaining these changes to GPs and clinicians so they in turn can advise patients.”
Professor Mark Baker, director of the NICE guidelines centre, noted that it was “important” that everyone affected by the changes was made aware of them “as soon as possible”.
“These are very welcome measures that will enable midwives to advise and support women”
As a result, he said NICE had taken “immediate steps” to amend its guidelines to reflect “this important change” to the drug’s licence – including guidance on epilepsy, bipolar disorder, depression in adults, and antenatal and postnatal mental health.
Nic Fox, director of primary and social care technology at NHS Digital said: “We have been working closely with the MHRA and GP system suppliers to ensure clinicians in primary care are informed of the risks of prescribing sodium valproate to certain patients.
“All GP systems have alerts applied and we are continuing to work with some of the suppliers to ensure these high visibility alerts are consistent across primary care,” he said. “These alerts ensure that GPs are prompted at the time of prescribing.”
Rachel Scanlan, professional advisor at the Royal College of Midwives, said: “These are very welcome measures that will enable midwives to advise and support women about this issue.
“We are actively putting this information out to our members including on social media and via the RCM’s website so that our members are informed about this important update,” she said.
“We have also updated our online learning package on epilepsy and pregnancy to reflect these changes,” she added.
Charities including Young Epilepsy, Epilepsy Action and the Epilepsy Society all welcomed the announcements from the MRHA and NICE, following years of campaigning.
- Epilepsy drug warnings during pregnancy ‘not reaching women’
- Nurses ‘must have time’ to discuss valproate risks
Carol Long, chief executive of Young Epilepsy, highlighted that sodium valproate could provide “life-changing support for many young people with epilepsy”.
“It is the third most-prescribed anti-epilepsy medication, however, the percentage of women who do not know the risks of taking the drug during pregnancy is far too high,” she noted.
“That information must be made clearer, and medical professionals must be given more support to understand and be proactive in flagging the risks,” she said.
“We know there are still far too many women who haven’t been made aware of the potential risks”
Simon Wigglesworth, deputy chief executive of Epilepsy Action, said: “Despite previous interventions, we know there are still far too many women who haven’t been made aware of the potential risks of taking sodium valproate in pregnancy.
“It is vitally important that healthcare professionals ensure that all women with epilepsy taking sodium valproate are reviewed in line with the new guidelines,” he said. “We are working closely with the MHRA on the implementation of these new guidelines.”
Clare Pelham, chief executive of Epilepsy Society, added: “It has taken many years to achieve these simple, straightforward and inexpensive healthcare improvements that will prevent babies being born with avoidable disabilities.”