Valproate and the pregnancy prevention programme

The PPP includes:

• Contraception and pregnancy prevention requirements 
• Distribution control – including whole-pack dispensing
• Education for healthcare professionals (HCPs) 
• Helping people taking valproate medicines understand teratogenic risk – including signing a risk acknowledgement form
• Annual review with the person’s specialist

Further details of the valproate PPP requirements can be found through the Medicines and Healthcare products Regulatory Agency (MHRA).

Does the PPP apply to all antiepileptics?

In June 2024, the MHRA introduced new safety measures, including a PPP for the anti-epileptic drug Topiramate (Topamax). Topiramate is now contraindicated in pregnancy and in people of childbearing potential, unless the conditions of a PPP are fulfilled.  For further information see the MHRA drug safety update ‘Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme‘

The PPP doesn’t currently apply to any other antiepileptics. Following a safety review of antiseizure medications in pregnancy by the Commission on Human Medicines (CHM) in 2021, lamotrigine (Lamictal) and levetiracetam (Keppra) were found to be safer than other antiepileptic drugs they reviewed. For further information, see the MHRA drug safety update ‘Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review‘ (January 2021). Information can also be found under the risk materials in the individual summary of product characteristics (SPC) on the electronic medicines compendium (emc) website

Who should enter the valproate PPP?

All adults and young people on valproate of childbearing potential must be entered into the PPP. The conditions of prevent/PPP need to be maintained during the entire duration of treatment with valproate. This includes patients who are switching to a therapy other than valproate – the conditions of prevent/PPP should be continued until valproate is discontinued.

Some people aren’t at risk of pregnancy. However, they should still be supported under the PPP, unless the specialist prescriber agrees there are compelling reasons to indicate that there is no risk of pregnancy. 

Reasons that indicate no risk of pregnancy might include people who can’t become pregnant (e.g. due to a hysterectomy, sterilisation, postmenopausal or if they’re not sexually active, and there’s certainty that sexual activity will not start during the period of teratogenic risk). Information on permanent or compelling reasons as to why the reproductive risks may not apply to a person can be found in clinical guidance on the gov.uk/MHRA website.

Further information can be found in the MHRA drug safety update ‘Valproate medicines (Epilim, Depakote): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met‘ (April 2018). It includes guides for the person on valproate, HCP guides and actions for pharmacists. Information can also be found under the risk materials in the individual SPCs on the emc website. 

Education for HCPs and people taking valproate

Here are the valproate PPP support/risk materials available (updated June 2025):

• Patient card – to be given by pharmacists to all adults and young people of childbearing potential who are dispensed valproate medicines to inform them of the risks. Provides key information for female patients receiving valproate on contraception and pregnancy prevention, and precautionary advice for men and their female partner to use effective contraception
• Patient guide for female and male patients – to be provided to all adults and young people of childbearing potential (or their parent/caregiver/responsible person) taking any medicine containing valproate. Provides information on the risks of valproate in pregnancy and the risks to male patients
• Healthcare professionals guide – for all prescribers, pharmacists and other HCPs involved in the care of adults and young people of childbearing potential using valproate medicines. Provides updated information on the risks of valproate in pregnancy and the risks for male patients, the new conditions for valproate prescribing and key points for patient discussions
• Annual risk acknowledgement form – for female patients under 55 years starting valproate and at annual review. The specialist and person prescribed valproate (or their parent/caregiver/responsible person) should sign at initiation and at treatment reviews at least every year. The person prescribed valproate should receive a copy of the form. One copy should be filed in the specialist notes and another copy sent to the person’s GP. It is used to support and record the discussion between the patient and specialist prescriber on the risks associated with valproate in pregnancy and to record the decision of the countersigning specialist. At subsequent annual reviews only one specialist is required
• Risk acknowledgement form for male patients. To support and record the discussion between the person and specialist prescriber of the risks associated with valproate in males under 55 years when starting treatment with valproate and to record the decision of the countersigning specialist. This is only to be completed at initiation of valproate
• Pharmacy poster – provides important actions for pharmacists dispensing valproate to patients
• MHRA safety leaflet ‘Epilepsy medicines and pregnancy‘ – can help explain the risks of valproate use
• MHRA infographics – developed by the MHRA to provide clarity for clinicians regarding valproate prescribing and those situations where a review by two specialists may be required

Further information on the valproate PPP and risk materials can be found in individual SPCs on the emc website. 

Further information on the new or updated safety and educational materials are now available on the MHRA June 2025 drug safety update. The updates reflect:

• Precautionary advice on the potential risk of neurodevelopmental disorders in children fathered by men taking valproate around the time of conception
• A risk of lower weight at birth for the gestational age in children exposed to valproate during pregnancy.

Prescribing and monitoring under the valproate PPP

Who can prescribe?

Valproate must be initiated and supervised by an experienced specialist prescriber for adults and young people of childbearing potential (see the valproate safety Measures for information on specialist signatories).

Prescribing

Valproate is used to treat epilepsy, bipolar disorder and for preventing migraine (unlicensed).

It is contraindicated for the treatment of migraine and bipolar disorder during pregnancy, and of epilepsy during pregnancy, unless there is no other suitable alternative.

When prescribing valproate, including under the PPP, consider that:

• Valproate can seriously harm an unborn child when taken during pregnancy and should not be prescribed in adults and young people of childbearing potential unless:
  • There are no other suitable alternative treatments (i.e. unless other treatments are ineffective or not tolerated) and
  • The person taking valproate is enrolled on the valproate PPP.
• Valproate must not be started for the first time in anyone under 55 years old unless:
  • There are compelling reasons that the reproductive risks do not apply – further information on permanent or compelling reasons as to why the reproductive risks may not apply to a person can be found in the MHRA’s clinical guidance and valproate guide for HCPs or
  • Two specialists experienced in the management of epilepsy or bipolar disorder independently consider and document on the risk-acknowledgment form that there is no other suitable treatment. For many people, other effective treatment options are available to treat bipolar disorder or epilepsy. A list of who might qualify as a second signatory can be found in the MHRA valproate safety measures
  • The CHM has advised that a review by two specialists is required for those initiating valproate under 55 years but not for men who are already taking valproate. The information considered by the CHM and the advice issued can be found in a Public Assessment Report. You can use the following MHRA infographics to clarify when a review by two specialists may be required for:
    • Adults and young people of childbearing potential patients under 55 years old
    • Men under 55 years old
    • Everyone 55 years and older
• Those who are pregnant and on valproate are recommended to be enrolled on the UK Epilepsy and Pregnancy Register as early in the pregnancy as possible.
• A risk acknowledgement form should be completed by the specialist prescriber with the person, signed at initiation and countersigned by a second specialist and treatment reviews at least every year. The person should receive a copy of the form. One copy should be filed in the specialist notes and another copy sent to the person’s GP. 

Please see the MHRA infographics which clarify the situations when a review by two specialists may be required and where a risk- acknowledgement form needs to be completed for a person prescribed valproate. 

• The person must understand the risks of valproate use in pregnancy and the need for effective contraception (the MHRA safety leaflet ‘Epilepsy medicines and pregnancy’ can help explain the risks)
• The person must be reviewed annually – at the annual specialist review, adults and young people of childbearing potential should be reviewed to re-evaluate treatment (where necessary), explain the risks and sign the risk-acknowledgement form. This will include the need for a second specialist signature if the person is to continue with valproate, and subsequent annual reviews with one specialist, unless the person’s situation changes. Note the MHRA update (February 2025) where a review by two specialists is required for initiating valproate under 55 years but not for men who are already taking valproate
• Under the valproate PPP, the person should be given the appropriate patient guide (patient guides are available for female and male patients)
• Primary care prescribers should check that the person under the valproate PPP has been reviewed by a specialist in the last year, is on highly effective contraception and has an up-to-date risk acknowledgement form

Additional prescribing advice for males on valproate 

A retrospective observational study has showed a possible increased risk of neurodevelopmental disorders in children born to males taking valproate in the three months prior to conception. For further information, see the Public Assessment Report on at gov.uk.

The September 2024 MHRA drug safety update for valproate use in men, highlighted the precautionary measures that are to be taken, in addition to the existing requirements in the January 2024 MHRA drug safety update for the introduction of the prescribing requirements in patients under 55 years of age (female and male). As men’s reproductive potential continues beyond 55 years, men older than 55 years on valproate should be counselled on the risk as appropriate.

• Advise men (of any age and irrespective of indication and route of administration) who may father children of the possible risks – at initiation of valproate or at their next regular treatment review or follow up
  • Counsel men on the risks using the MHRA visual risk communication diagram (this information does not replace the overall discussion on risks and benefits which would lead to an informed prescribing decision)
• Discuss family planning and contraception with men
  • If they are planning a family in the next year, then refer to a specialist to discuss most appropriate treatment options at the next regular treatment review
  • Advise them on the use of contraception using the MHRA Advice for male patients on valproate to use contraception
  • Advise them not to donate sperm during valproate treatment and for three months after stopping valproate
  • As a precaution, it’s recommended that they and their sexual partners should use effective birth control (condoms and another form of female contraception) if their partners are able to get pregnant, and for at least three months after stopping to allow for one complete sperm cycle to be free from valproate exposure. However, if their partners are already using highly effective contraception (e.g. intrauterine device or implant), then condom use is not required to prevent pregnancy

A February 2025 MHRA drug safety update highlighted that two specialists need to review all people under 55 years of age initiating valproate, but the CHM advised that will not be required for men already taking valproate. The MHRA have infographics to clarify when review by two specialists may be required for:

• Men under 55 years old
• Everyone 55 years and older

Further details on prescribing valproate can be found on the BNF website, MHRA guidance for HCPs, Association of British Neurologists guidelines for valproate prescribing (adult), individual SPCs on the emc website and the MHRA collection of information and guidance for people on valproate and for HCPs on the reproductive risks of valproate and new safety measures introduced to reduce these risks.

Dispensing valproate for all people, including under the valproate PPP

When dispensing valproate, you and your teams should:

• Dispense in original packs – you must dispense the manufacturer’s original full pack for all NHS and private prescriptions of valproate-containing medicines. For further information, see the MHRA ‘Full pack dispensing of valproate-containing medicines’ guide
• Not repackage valproate-containing medicines into plain dispensing packaging, unless in exceptional circumstances (see below).
• Consider quantity – to provide the manufacturer’s original full pack closest to the amount written on the prescription you must either round the quantity up or down
• Consider that repeat prescriptions for valproate can be provided 
• Provide a patient-information leaflet (PIL) when dispensing licenced valproate-containing medicines. copies of the PIL can be downloaded from the emc website or MHRA website
• Provide a patient card to all adults and young people of childbearing potential every time you dispense them valproate medicines. Detach patient cards on packs and give to them
• Be careful when labelling to not cover patient safety warnings associated with taking valproate-containing medicines or the patient card.
• Remind your team of the dispensing requirements (use this dispensary A4 poster)
• Consider brand continuity in antiepileptic use (the MHRA drug safety update: ‘Antiepileptic drugs: updated advice on switching between different manufacturers’ products‘ may help you)
• Be aware that people using services (such as prescription collection and delivery) may have little, if any, personal contact with pharmacists. 
• Provide counselling to all adults and young people of childbearing potential as appropriate

Exceptional circumstances

The manufacturer’s original full pack does not have to be supplied where a risk assessment indicates the need for alternative packaging (e.g. the person does not understand what the medicine is for, how to take it correctly or suffers from confusion). You must also provide a PIL for licensed valproate-containing medicines.

Counselling

Advise all people on valproate to read the PIL and packaging as a reminder of key safety messages. 

Discuss the following:

• The medicine – what it is, how it works and how to use it
• The importance of adherence
• Inform on the benefits and risks of treatment
• Side/adverse effects – make sure the person is aware what signs and symptoms to look out for, what to do if they occur and when to seek medical attention and advice
  • Advise people or their carers on how to recognise the signs and symptoms of blood or liver disorders and pancreatitis, and to seek medical attention if these develop. See the latest version of the BNF for further guidance
  • Advise people of the need for monitoring, including liver function (before starting therapy and for the first six months) and full blood count (before starting therapy and before surgery). See the latest version of the BNF for further guidance
  • Any suspected side effects should be reported through the Yellow Card Scheme. You may also find our pharmacy guide helpful to support patients with this.
• Advise adults and young people to read the PIL and patient guides (male and female) for possible risks and what to do if they are planning pregnancy, become pregnant or think they might be pregnant. Additionally, refer to a specialist.
  • Those planning a pregnancy should be advised to schedule an appointment with their prescriber to review treatment and to continue with contraception and valproate treatment in the meantime
  • If there is an unplanned pregnancy while they are taking valproate medicines, advise the person to NOT stop their treatment and to arrange to see their prescriber urgently to review treatment
• Remind people to avoid abrupt withdrawal. They should not stop treatment without first talking to, or unless advised by, an HCP – there is a risk of status epilepticus and sudden unexpected death in epilepsy
• Alcohol – it’s recommended to not drink alcohol while taking valproate 
• Driving – provide driving advice for people using valproate – see the PIL and SPC on the emc website and DVLA website
• Advise people to never share their medicines with anyone
• Referrals – make sure the person is aware when to see a prescriber (see ‘When to refer’ below)
• Interactions – make sure the person is aware to check interactions with a pharmacist before starting any new medicines
• Storage and disposal – advise people on how to correctly store and to return any unused medicines to a pharmacy for disposal when treatment finishes
• Health promotion – provide general lifestyle and wellbeing advice where appropriate, including diet, exercise, smoking cessation, weight and blood pressure

Additional advice for all adults and young people of childbearing potential

• Discuss the risk of teratogenicity associated with valproate and adults and young people of childbearing potential 
• Advise that any concerns about the reproductive risks of valproate-containing medicines should be discussed with their doctor, pharmacist or HCP.
• Check the person has the relevant valproate patient guide (for female and male patients) and patient card. If not, provide them where needed, ask that they read keep them safe, as they contain important safety information.
• Check the person has a copy of the risk acknowledgement form.
• Check the person is attending annual reviews with their specialist as appropriate – emphasise the importance of their annual specialist review and refer them to their prescriber or specialist where needed.
• Check the person understands the risks of using valproate in pregnancy and is using appropriate contraception – refer them to their prescriber or specialist where needed.
• Adults and young people of childbearing potential must enter the PPP (see the section on who should enter the PPP, above).
• Check and counsel on correct contraception use if under the PPP.
• The MHRA safety leaflet on epilepsy medicines and pregnancy can be provided to help explain the risks.

For additional advice for men taking valproate, see the above section on advice on prescribing valproate for men.

For further information on side effects, counselling and when to refer, see the BNF and relevant SPCs on the emc website.

You may also find our pharmacy guide on counselling people on the use of medicines useful.

When to refer

Refer to a specialist if people are planning pregnancy, become pregnant or think they might be pregnant. 

Refer men who are planning a family within the next year to discuss their treatment options with an HCP, as a precaution.

Refer to a specialist if people wish to discuss their treatment options.

Refer for prenatal counselling if an adult or young person of childbearing potential reports they are pregnant or planning a pregnancy with a man on valproate (including those undergoing IVF).

Further information

Product, clinical and prescribing information

• BNF
• emc for SPCs
• NHS England sodium valproate page – includes a letter for all women and girls aged 12 and over on valproate
• NICE ‘Epilepsies in children, young people and adults‘ (published April 2022, updated January 2025)

Resources for people on valproate

• NHS South East Clinical Delivery and Networks – the South East Regional Clinical Quality Improvement team have worked with clinicians and people using health services to develop an information leaflet to support person-centred, informed discussions about how to take valproate as safely as possible. The leaflet has been translated into 30 languages.
• NHS England decision support tool: ‘Is valproate the right epilepsy treatment for me?’ – this is for clinicians to use with people with epilepsy or bipolar disorder to help them understand the potential risks and benefits of valproate and decide whether to start or keep taking it.
• MHRA safety leaflet: ‘Epilepsy medicines and pregnancy’ – this can help people on epilepsy medicines understand the risks.

MHRA drug safety updates

• Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell▼): updated safety and educational materials to support patient discussion on reproductive risks (June 2025).
• Guidance: Valproate – reproductive risks (June 2025).
• Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell▼): review by two specialists is required for initiating valproate but not for male patients already taking valproate (February 2025).
• MHRA drug safety update ‘Valproate use in men: as a precaution, men and their partners should use effective contraception‘ (September 2024).
• MHRA Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell▼): new safety and educational materials to support regulatory measures in men and women under 55 years of age (January 2024).
• MHRA National Patient Safety Alert: Valproate: organisations to prepare for new regulatory measures for oversight of prescribing to new patients and existing female patients (October 2023).
• MHRA ‘Full pack dispensing of valproate-containing medicines’ guide – this is for dispensing of valproate-containing medicines in the manufacturer’s original full pack, following amendments to the Human Medicines Regulations. It applies to pharmacists in England, Scotland and Wales, and is for good practice by pharmacists in Northern Ireland.
• MHRA drug safety alert valproate: reminder of current Pregnancy Prevention Programme requirements; information on new safety measures to be introduced in the coming months (December 2022).
• MHRA drug safety update: Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review (January 2021).
• MHRA Public Assessment Report of antiepileptic drugs: review of safety of use during pregnancy (January 2021).
• MHRA drug safety update: Valproate (Epilim, Depakote) pregnancy prevention programme: updated educational materials (February 2020).
• MHRA drug safety update: Valproate medicines and serious harms in pregnancy: new Annual Risk Acknowledgement Form and clinical guidance from professional bodies to support compliance with the Pregnancy Prevention Programme (April 2019).
• MHRA drug safety update: Medicines with teratogenic potential: what is effective contraception and how often is pregnancy testing needed? (March 2019).
• MHRA guide: Valproate use by women and girls (2018) – This is guidance on the risks of taking valproate medicines during pregnancy, including current advice, support for people on valproate, network links and clinical resources.
• MHRA drug safety update: Valproate medicines: are you acting in compliance with the pregnancy prevention measures? (December 2018).
• MHRA drug safety update: Valproate Pregnancy Prevention Programme: actions required now from GPs, specialists, and dispensers (December 2018).
• MHRA drug safety update: Valproate medicines (Epilim, Depakote): Pregnancy Prevention Programme materials online (May 2018).
• MHRA drug safety update: Valproate medicines (Epilim, Depakote): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met (April 2018)
• MHRA drug safety update: Antiepileptic drugs: updated advice on switching between different manufacturers’ products (November 2017).

Other useful guidance

• The General Pharmaceutical Council sodium valproate resources and information.
• A pan-college guidance document endorsed by RPS: ‘Valproate Use In Women and Girls Of Childbearing Years‘ (March 2019) – This was developed by medical royal colleges.
• ‘Safe supply of valproate medication’ – A joint pharmacy resource that includes a decision pathway and key points for conversations between pharmacy teams and those who have been prescribed valproate medicines. Developed in partnership by the pharmacy organisations represented on the MHRA’s Valproate Stakeholder Network, including the Community Pharmacy Patient Safety Group, Community Pharmacy Northern Ireland, Community Pharmacy Scotland, Community Pharmacy Wales, the RPS, the Pharmacy Forum of Northern Ireland and the Pharmaceutical Services Negotiating Committee.
• Company Chemists’ Association clinical audit on valproate safety (June 2018).
• All Wales Therapeutics and Toxicology Centre: sodium valproate information hub.
• Medicines and Pregnancy Registry
• UK Epilepsy and Pregnancy Register.