MHRA changes licence for valproate medicines to protect those of childbearing potential

The Medicines and Healthcare products Regulatory Agency (MHRA) has implemented changes to the licence for valproate medicines — Epilim, Depakote and generics used to treat epilepsy and bipolar disorder — in the interest of public safety.

Valproate, if taken during pregnancy, can lead to children being born with birth defects and persistent developmental disorders. From now on, valproate must not be prescribed to women or girls of childbearing potential unless they are enrolled in the pregnancy prevention programme (PPP).

To follow this change, healthcare professionals will need to ensure the patient is enrolled in the PPP and will be required to obtain a completed risk acknowledgement form when the treatment is reviewed by a specialist — which should be performed annually at least. Women and girls who are currently prescribed valproate should contact their GP to arrange to have their treatment reviewed but prescribed medication should not be discontinued without medical advice.

Further support of these regulatory changes will include smaller pack sizes so that monthly prescribing is encouraged and a warning image on valproate labelling.

These new regulatory measures are being supported across the NHS with other authorities also making alterations so that prescribing behaviour is promptly changed. 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.

In parallel, the National Institute for Health and Care Excellence (NICE) 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 guideline on epilepsy. This will specifically focus on areas where valproate is currently regarded as the drug of choice and where this conflicts with the new position.

These measures should help reduce the number of pregnancies exposed to valproate medicines and will make sure all women and girls of childbearing potential are aware of the risks.

“Patient safety is our highest priority. We are committed to making sure women and girls are aware of the very real risks of taking valproate during pregnancy. However, we also know it is vitally important women don’t stop taking valproate without first discussing it with their doctor,” said Dr June Raine, director of MHRA’s Vigilance and Risk Management of Medicines Division. “This regulatory position has been developed through close collaboration with professional bodies, health system organisations, and patient and campaign groups. I would like to particularly thank the families involved in the Valproate Stakeholder Network who have shared their experiences and expertise with us. Their support will help keep future generations of children safe.”

“Our priority is always patients’ safety, so I welcome this decision to take strong actions to protect women and children,” added health minister Lord O’Shaughnessy. “The focus will now be on explaining these changes to GPs and clinicians so they in turn can advise patients.”

“NICE welcomes restricting the use of valproate in women of childbearing potential,” explained Professor Mark Baker, director of the Centre for Guidelines at NICE. “It’s important that everyone affected by these changes is made aware of them as soon as possible. We have therefore taken immediate steps to amend our guidelines on the diagnosis and management of epilepsies, the assessment and management of bipolar disorder, depression in adults, and antenatal and postnatal mental health to reflect this important change to the drug’s licence.

“We will use our communications networks to highlight the changes, both to healthcare professionals and to patients, to help ensure that the number of children exposed to valproate through their mother during pregnancy is kept to an absolute minimum.”

Nic Fox, director of Primary and Social Care Technology at NHS Digital stated: “This is a good example of how IT systems can support important issues affecting public health. 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. These alerts ensure that GPs are prompted at the time of prescribing.

“We have also worked with community pharmacy dispensing system suppliers to ensure that the alerts are also shown when prescriptions are dispensed. This includes changes to prescription labels so that patients are made aware of the risks and the need for reliable contraceptive precautions. We will continue to work with supplier partners in evolving system to maximise safety and minimise burden on clinicians and patients as guidance evolves.”

“Stronger regulation over the use of valproate is welcome and will help ensure women get the advice and care they need,” said Matthew Jolly, national clinical director for maternity and women’s health at NHS England. “It is important pregnant women discuss their medication with their doctor and crucially do not stop taking it before seeking advice.”

“We welcome this action to reduce the risk of physical and developmental problems in children born to mothers who have taken valproate during pregnancy. Our clinical guideline on the management of epilepsy in pregnancy recommends that exposure to sodium valproate and other anti-epileptic drugs should be minimised by changing the medication prior to conception, as recommended by an epilepsy specialist after a careful evaluation of the potential risks and benefits,” revealed Mr Edward Morris, vice president for clinical quality at the Royal College of Obstetricians and Gynaecologists. “It’s important to note that stopping medication for long-term conditions completely or altering the dose can pose a serious risk to both mother and baby. Women are advised to seek advice from their GP and/or specialist team before conception or as soon as they are aware that they are pregnant. For women with epilepsy, the lowest effective dose of the most appropriate anti-epileptic drug should be prescribed and they should be looked after by a specialist team throughout pregnancy.”

Professor Helen Stokes-Lampard, chair of the Royal College of GPs, commented: “GPs are acutely aware of the risks associated with prescribing sodium valproate to women of childbearing age and we welcome this change in legislation as a logical way forward to help ensure our patients’ safety. However, any patients currently taking sodium valproate should not stop doing so without seeking expert medical advice.

“As a general rule, it is important that patients read and take heed of warnings on the packets of any medication they are taking — and that any woman on long-term medication speaks to their GP if they are planning to have a baby.”

“The Royal Pharmaceutical Society fully supports these new measures to ensure women understand the risks of taking sodium valproate during pregnancy. They must get the right information from health professionals in order to make informed choices about their health and parenting options,” explained Professor Ash Soni, president of the Royal Pharmaceutical Society. “Valproate is an effective medicine and women should never suddenly stop taking it without talking to a health professional. Pharmacists are ideally placed to give information and support when providing sodium valproate and are committed to reducing harm from medicines, enabling women to make the choices that are right for them.”