General Medical Council &General Pharmaceutical Council – Strengthened Initiatives Surrounding Prescribing of Sodium Valproate

18 June 2021

This week with the announcement of 20,000 women in the UK receiving a letter about the risks of Sodium Valproate in Pregnancy we have worked and liased with the General Medical Council and The General Pharmaceutical Society in producing further communications and a Video to highlight the risk.

Here at INFACT we welcome and thank all involved in this round of communications and continued effort for safer prescribing with Sodium Valproate.

General Medical Council : This case study is about discussing the risk of taking sodium valproate with a mother who’s been prescribed it for several years. 

We’ve developed this case study with the General Pharmaceutical Council and the Nursing and Midwifery Council. While the characters are fictional, the case study is based on several people’s lived experiences, which were generously shared by patients and clinicians.

It highlights the risk of harm created by taking sodium valproate (‘valproate’), a medication for epilepsy that can cause birth defects if taken during pregnancy. Valproate was one of the interventions considered by the Independent Medicines and Medical Devices Safety Review, which reported in July 2020. The Review highlighted that many women had not been properly informed about the risks of taking valproate.  

The MHRA’s strengthened regulatory position should mean that no more women are prescribed sodium valproate without discussing the risks of harm and having a Pregnancy Prevention Plan in place. However, for some women already taking valproate but unaware of the risks this can create complex situations and difficult conversations with their healthcare providers. Repeat prescription (GP) 

Learning overview

Be familiar with guidelines and developments that affect your work. 

Make sure any repeat prescription you sign is safe and appropriate.

Don’t assume a patient’s already been given the information they need about risks of harm. If you haven’t personally spoken to a patient about medication they’re taking, it may be particularly important to review their decision to take it. 

Scenario

Dr Wright receives a repeat prescription request for sodium valproate from Millie, who is new to the practice. She sees that a valproate annual risk acknowledgement form has not been completed. 

After reviewing Millie’s medical record, Dr Wright becomes concerned because it appears that: 

  • Millie has been prescribed valproate continuously since 2010 
  • she hasn’t seen a neurologist since 2012 
  • she doesn’t appear to be on the pregnancy prevention programme (PPP). 

Dr Wright wonders whether Millie has been advised about the risks of taking valproate during pregnancy. She notes that Millie’s two children were both born before 2018 when the Medicines and Healthcare products Regulatory Agency (MHRA)’s strengthened regulatory position came into force. This made it compulsory for GPs to make sure, each time a repeat prescription is issued, that women of childbearing potential on valproate are: 

Dr Wright wonders whether Millie’s valproate use throughout pregnancy may have adversely affected her children.

She asks the practice receptionist to phone Millie and ask her to attend the surgery for a medication review with Dr Wright as soon as possible.Medication review (GP) 

General Pharmaceutical Council

This week the General Pharmaceutical Council have also reiterated communications to Pharmacists in England Scotland and Wales. In collaboration with GPC we have created a video explaining the role the Pharmacist has when prescribing Sodium Valproate

Valproate updates , 

We wanted to share with you a letter that NHS England & Improvement are sending to all women and girls taking valproate in England. The letter includes a reminder about the risks of taking valproate during pregnancy and the need for an annual review. 

This letter also encourages patients to speak to their doctor or nurse specialist. Your patients taking valproate may also ask to speak to you about the letter and you may want to check with your patients if they have received the letter and if they have any questions about their valproate prescription. 
Medicines in Pregnancy Registry NHS Digital and the Medicines and Healthcare products Regulatory Agency (MHRA) have developed a valproate registry.
Data collected in England between April 2018 and September 2020 shows: 
47,532 females (ages 0-54) were prescribed one or more prescriptions for valproate in one or more months within the reporting period
180 females were prescribed valproate while pregnant  
238 females stopped receiving prescriptions of valproate prior to their pregnancy  

Supplying valproate safely to women and girls Pharmacy professionals have a key role in supplying valproate safely. Valproate must not be used in any woman or girl able to have children unless there is a pregnancy prevention programme (PPP) in place.

For women and girls, when they are dispensed valproate, they should expect:to be provided with a Patient Card every time valproate is dispensedfor valproate to be dispensed with a copy of the patient information leaflet, and if repackaged, with a warning on the container supplied to be reminded of the risks in pregnancy and the need for highly effective contraception, and a reminder of the need for annual specialist review to be asked if they have received the Patient GuideYou must make sure that the patient label is not placed over the warning labels or warning sticker on the box. Women taking valproate have shared with us examples of where this has happened. 

When patients are visiting pharmacies for pregnancy tests or emergency hormonal contraception remember to ask them about any medications they are taking so you can provide further advice if their medicines are teratogenic.

Find out more about what you need to do in our Focus on supplying medicines safely: sodium valproate.

Watch our film where we speak to two women whose children were affected by exposure to sodium valproate during their pregnancies, to find out why it’s so important to make sure that women are made aware of the risks when dispensing sodium valproate. Valproate case study This in-depth case study explores patient Millie’s interactions with the different healthcare professionals she meets. It explores how to approach difficult conversations and highlights the important role all healthcare professionals have in prescribing and dispensing valproate safely.  How pharmacies can support women and girls taking valproate Find out more in this example of notable practice on supporting people taking valproate from our Knowledge Hub. 

Our inspectors check the pharmacy team are following the requirements of the Pregnancy Prevention Programme during inspections.

Sodium Valproate: The Fetal Valproate Syndrome Tragedy

Written by Sharon Hartles

In this article, Sharon Hartles reflects upon the significant impacts of avoidable harms that have been perpetuated for decades as a result of medical negligence on behalf of the regulator (Committee on Safety of Medicines) that advised the UK Licensing Authority on the safety of medicines and the manufacturer of Epilim (Sanofi). Sharon Hartles is a member of the Open University’s Harm and Evidence Research Collaborative.

Sodium Valproate

Sodium valproate, marketed as Epilim in the UK, has been linked to physical, developmental and neurological harms in the human fetus.

ALAMY https://www.thetimes.co.uk/article/sinn-f-in-senator-urges-inquiry-for-epilim-babies-hr6vlklmf

In the UK, Epilim is the dominant sodium valproate medication used to treat patients at risk of epilepsy associated convulsions. Epilim is an effective anti-convulsant medicine (epilepsy drug) and for this reason it has been licensed for usage since 1973. However, Epilim is also a teratogen; thus exposure to this drug causes an increased risk of physical, developmental and neurological harms in the human embryo or fetus.

Given the fact that sodium valproate is harmful, wherever possible it clearly should not be prescribed to female patients of childbearing age.  Despite this, the regulators and Sanofi, the company responsible for manufacturing and marketing Epilim (Sanofi acquired the company from Reckitt-Labaz in or around 1980) chose to keep patients in the dark for decades and did not disclose the known associations. As a consequence, patients were unable to make informed choices, which has resulted in the preventable fetal valproate syndrome tragedy.

According to The independent Medicines and Medical Devices Safety Review, congenital birth defects associated with in utero exposure to sodium valproate include:

  • Neural tube defects (NTDs), such as spina bifida 
  • Cleft lip and palate
  • Facial and skull malformations
  • Heart, kidney, urinary tract and sexual organ malformations
  • Limb defects
  • Developmental delay
  • Autism Spectrum Disorders (ASDs)
  • Attention Deficit Hyperactivity Disorder
  • Ear malformations and auditory processing
  • Skeletal malformation
  • Arthritis in older children
  • Effects on the endocrine system
  • Sexual identity problems (which occur due to a mismatch between genital development and neural / sexual identity development).
  • Psychomotor issues.
  • Withdrawal symptoms – associated with prenatal sodium valproate exposure.

Fetal valproate syndrome harms are widely accepted within the clinical and regulatory community, including by: the National Institute for Health and Clinical Excellence (NICE), the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).

During the 1960s and 1970s, articles were published drawing attention to the concerns about the teratogenicity and anti-epileptic (anti-convulsant) medication this included research by: Lawrence, 1963Janz and Fuchs 1964Meadow 1968Speidel and Meadow 1972,  Lowe, 1973Fedrick 1973Hill 1974Barr, 1974 and Hanson and Smith 1975. Yet, despite the known harms, documents uncovered from The National Archives revealed that in 1973, the Committee on Safety of Medicines (a precursor to the  Medicines & Healthcare products Regulatory Agency) thought it best not to make patients aware of the dangers because “it could give rise to fruitless anxiety”. 

The controversy surrounding the abhorrent failure to communicate the preventable risks to clinicians and patients was evidenced again because by the early 1980s the regulator and manufacturer was in possession of sufficient information to conclude that Epilim increased the risk of congenital abnormalities. Even though the links between the exposure to sodium valproate and the increased risk of harms to a fetus were well-documented, patients were not informed directly of the link until 2005. In some cases care pathways for women of child-bearing age were not established until 2016. In February 2018, the European Medicines Agency put in measures to avoid valproate exposure in pregnancy.

A visual warning of the pregnancy risks (in the form of text) with other warning symbol on the outer carton

A visual warning of the pregnancy risks (in the form of text) with other warning symbol on the outer carton.

https://www.chemistanddruggist.co.uk/cpd-article/valproate-pregnancy-prevention-programme

The fetal valproate syndrome tragedy (medical negligence) was entirely avoidable, resulting from a regulation failure and decades of inaction by successive governments to safeguard patients. The true number of individuals’ harmed by sodium valproate in utero since it was licensed in 1973 in the UK is unknown, however, the consensus estimate is around 20,000.  More recent evidence suggests that the medical problems associated with fetal valproate syndrome may be passed down the generations.

The role that the regulator and the manufacturer Sanofi have played in creating and perpetuating this tragedy is evident, therefore financial redress should be paid to all those affected by fetal valproate syndrome.

Currently, 27,000 women of child bearing age are taking valproate in the UK. On 2nd March 2021, in the House of Lords, James O’Shaughnessy, Vice-chair for the All-Party Parliamentary Group for First Do No Harm, reported that since June 2020, 150 babies had been born suffering harms due to sodium valproate exposure. Therefore it is imperative that the Government find ways to minimise the risk of harms to future babies. Beyond this, lessons must be learned and mechanisms put into place to ensure avoidable systemic failures on this scale do not happen again. 

Letter released to women and girls taking Sodium Valproate

NEWS RELEASE 14/6/21

NHS Issues Advice To Girls And Women Taking Sodium Valproate For Epilepsy

20,000 women and girls will this week be reminded of risks during pregnancy while taking an epilepsy drug, as part of the NHS’s drive to increase patient safety.

Over the coming days letters are being sent to females in England aged between 12 and 55 who are currently recorded as having an active prescription for the drug, Sodium Valproate, outlining a number of actions to take if they are pregnant, trying for a baby or have not had a recent medication review.

Sodium valproate is a drug that can be used to treat epilepsy and bipolar disorder, however babies can be harmed if the person taking the drug becomes pregnant.

The NHS is now sending reminder letters as part of the organisation’s drive to inform patients and prevent future risks.

The letter from the NHS Director of Patient Safety, Dr Aidan Fowler, will urge those with an active prescription to continue their treatment course until their doctor tells them otherwise, but to:

  • Continue to take contraceptive measures, ideally the implant or coil, while they are taking valproate;
  • Speak to their GP immediately if they think they may be pregnant;
  • Seek a medicines review from their GP if they haven’t received one in the last 12 months, and;
  • Speak to their doctor if they are keen to try for a baby, before coming off contraception.

The reminder is part of the NHS’ ongoing response to former health Minister Baroness Cumberlege’s Independent Medicines and Medical Devices Safety Review, published last year.

A new data registry has also been established, managed by NHS Digital, to better track prescriptions to women.

NHS Patient Safety Director, Dr Aidan Fowler, said:

“Valproate is the best treatment available for a small group of people with very complex illnesses, so it’s vital those who have an active prescription for it to continue taking it until they are told otherwise by their GP or consultant.

“It’s vital too however that everyone understands the risk that doing so poses to your unborn child if you are pregnant, and this letter is a reminder of information that every woman and girl of childbearing age should receive from their doctors when the drug is first prescribed”.

Sodium valproate was approved for use in 1974 and has always carried warnings for doctors about the possible risks if it is taken while pregnant. These have been strengthened over the decades as more data has become available about higher rates of physical birth defects, autism and child developmental problems.

Due to this risk, in 2018 the heads of all medicines agencies in the UK issued a joint edict saying that all women and girls who could potentially conceive should be provided with and urged to use contraception for as long as they are taking valproate, even if they are not sexually active.

Doctors are expected to discuss the risks with patients as part of the shared decision around prescribing valproate, and put in place a pregnancy prevention plan to eliminate risk if it is prescribed, or use other forms of treatment if the patient wishes to have a baby.

Emma Murphy – Managing Director of INFACT

“We welcome this letter of communication being sent to all females of childbearing age informing them of the risks of Valproate in Pregnancy. This is something that should have been done from the very beginning and it has been a long and arduous campaign by INFACT to reach this goal. We are not only glad for ourselves that now Governing Bodies are taking these steps but most importantly for the patients prescribed the drug and the potential damage to the lives of unborn children”

March in Review

The start of the month saw INFACTs new Website Facebook / Twitter and Just Giving Page all go live with our following steadily growing. We also started working with Anna Christian Campaigns whose help and advice has been invaluable and we are so happy to have her backing as we move forward.

As the Remit deadline approached mid March, the parents submissions being sent to us increased in number and were all included along with submissions sent to Norman Lamb MP, INFACTs medical team reports, and INFACTs own extensive files and were all passed to Michael Mansfield’s team at Nexus Chambers for them to start finalising and drafting his report which is due back early April.

We also finished sending out registration emails and numbers to everyone on our database which now stands at 1200+ . We had quite a lot of issues with people registering with one email but then using a different one for their day to day business and also Facebook user names being different to registered names on the database.
If anyone still has worries about their registration number please do get in touch at
Infact.org.uk@gmail.com

We travelled down to Parliament twice, welcoming new MPs onto the APPG. We also held an extremely well attended APPG meeting in which the direction of the group was agreed.

INFACT welcomed the announcement and recommendations from European Medicines Agency  and MHRA that no woman of child bearing age is to be prescribed Valproate unless she is on the newly introduced Pregnancy Prevention Plan which means:

Valproate medicines are now therefore contraindicated, i.e. must not be used, in girls and women able to have children unless the terms of a special pregnancy prevention programme are followed. These include:

  • an assessment of each patient’s potential for becoming pregnant,
  • pregnancy tests before starting and during treatment as needed,
  • counselling about the risks of valproate treatment and the need for effective contraception throughout treatment,
  • a review of ongoing treatment by a specialist at least annually,
  • introduction of a new risk acknowledgement form that patients and prescribers will go through at each such annual review to confirm that appropriate advice has been given and understood.

We attended 2 high level meetings, in one of which we were invited onto the Expert Working Group at MHRA which was a very proud moment for INFACT. Whilst we cant divulge the discussions of these meetings due to the content and confidential nature we can say the direction in which the Valproate issue is now travelling is extremely positive. We will update on this as and when we can.

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This month understandably has also seen us receive increasing enquiries about the Cumberlege Review. We can confirm that NO “Terms of Reference” have yet been set, which basically means nothing has been asked for in respect of that Review and a start date has not been given either.
Whilst the Michael Mansfield QC report will eventually filter into the Cumberlege Review, the reason INFACT have legal representation for our remit is an entirely separate matter from the Cumberlege Review. It is now more important than ever that you or anyone you know who may have been harmed by Sodium Valproate are registered on our Database https://www.surveymonkey.co.uk/r/FR8N6B3

With dates in the diary already, April is set to be another busy month for INFACT and all donations to the Just Giving Pageto help with the ongoing fight for our children’s future which is now closer than ever, no matter how small are all greatly received.

We thank all our team who are working extensively and productively.

 

 

 

Campaign Update

After returning from Parliament yesterday INFACT can confirm that all submissions received through the APPG have now been passed to Michael Mansfield’s team at Nexus Chambers.

The APPG for Valproate and other AEDs in Pregnancy will continue to focus on its Campaign in Parliament whilst INFACT now move forward with the backing of the APPG and Michael Mansfield QC.

INFACT have now instructed for all documentation and submissions in relation to the Sodium Valproate Campaign be reviewed and drafted by Michael Mansfield QC.