High risk medicines: valproate

Sodium valproate and valproic acid are known collectively as valproate.

Brands include: 

• Epilim
• Depakote
• Convulex
• Episenta
• Epival
• Syonell
• Belvo
• Dyzantil. 

There are other generic brands.

Valproate is licensed for use in epilepsy and bipolar disorder. It is also used off-label for: 

• depression
• neuropathic pain
• dementia
• migraine.

Valproate and reproductive risks

Following several alerts, the Medicines and Healthcare products Regulatory Authority (MHRA) have issued several drug safety updates alongside a National Patient Safety Alert.

Taking valproate during pregnancy poses a significant risk of birth defects and developmental disorders.

One study suggests that children may have an increased risk of neurodevelopmental disorders if their fathers took valproate in the 3 months before the child was conceived, compared with fathers who took other antiseizure medicines.

As a result, people must use effective contraception:

• a highly effective method, such as an intrauterine device (IUD) or contraceptive implant, or
• 2 complementary methods of contraception, including a barrier method.

User dependent methods of contraception are those that require proper use to be effective. These methods include:

• condoms
• caps
• diaphragms
• oral contraceptive pills (COC)
• fertility awareness-based methods.

Frequent pregnancy testing should also be carried out.

Advice for providers

Providers must ensure that valproate must not be started in new patients (male or female) under 55 years old.

If valproate is required, 2 specialists must independently consider and document that:

• no other effective or tolerated treatment is available, or
• there are compelling reasons why the reproductive risks do not apply.  

The Commission on Human Medicines has advised that for males already taking valproate, a review by 2 specialists is not required. 

Valproate Pregnancy Prevention Programme

The MHRA update advises:

"Valproate must not be used in any woman or girl able to have children unless there is a Pregnancy Prevention Programme (PPP) in place. This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant."

At their next annual specialist review, women of childbearing potential and girls taking valproate should be reviewed using a revised valproate Risk Acknowledgement Form. This now includes:

• the need for a second specialist signature if the patient is to continue with valproate
• subsequent annual reviews with one specialist unless the patient’s situation changes.

Under the Pregnancy Prevention Programme, healthcare professionals are responsible for prescribing valproate safely.

Considerations for providers and staff

The Pregnancy Prevention Programme applies to all women able to have children taking a medicine containing valproate. The only exception is where the specialist considers there is no risk of pregnancy. For example, pre-menarche or post-menopausal.

The reasons for not enrolling on the programme should be recorded on the annual Risk Acknowledgement Form. This should be signed by the woman or their responsible person as necessary.

Providers of adult social care and their staff should:

• identify women who are able to have children  and who are taking valproate - you should not assume that a woman with a learning disability is not sexually active
• support women to attend their GP and/or specialist appointments for review
• work with healthcare professionals to provide information about the Pregnancy Prevention Programme. This should be in an accessible format where necessary, for example easy read
• hold a copy of the annual Risk Acknowledgement Form if the woman is unable to do so
• proactively support women with their contraceptive needs, where necessary.

For valproate use in men:

• You should not assume that a man with a learning disability is not sexually active.
• Identify males on valproate and ensure effective contraception (birth control) for their female partner during valproate use and for 3 months after stopping valproate (the time needed for new sperm to be formed).
• Male patients aged under 55 years being started on valproate are required to complete a Risk Acknowledgement Form with a healthcare professional. This does not need to be completed annually.
• Men should not donate sperm when taking valproate or for 3 months after stopping valproate treatment.

If a pregnancy occurs, you must support women to seek advice from a specialist as soon as possible.

Prescribers and dispensers

Healthcare professionals who seek to prescribe or dispense valproate to their female patients must make sure this is within the terms of the Pregnancy Prevention Programme .

This includes the completion of a signed Risk Acknowledgement Form when their treatment is reviewed by a specialist, at least annually for females and only at the start of treatment for males.

Prescribers are encouraged to use monthly prescriptions to support original pack dispensing.

Pharmacists

Pharmacists must support valproate use by:

• dispensing valproate-containing medicines in the original pack where possible so that patients receive all the warnings on the box, as well as patient card and package leaflet
• adding a pictogram/warning image on valproate labelling where possible
• ensuring the patient has received the female patient guide or male patient guide as appropriate.