Valproate-containing medicines▼ prescribing guidance (Formulary: Medicines management)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Audience

  • North NHS Highland only
  • Primary and Secondary Care
  • Adults and Children
Important: Advise patients NOT to stop valproate, unless advised by their specialist.
Valproate-containing medicines are sodium valproate, valproic acid and valproate semisodium.

Valproate use and reproductive risk

Valproate is used in the treatment of epilepsies, bipolar affective disorder and migraine prophylaxis (unlicensed), but it has significant teratogenicity and potential for reproductive toxicity.

Exposure to valproate in pregnancy is associated with physical birth defects in 11% of babies and neurodevelopmental disorders in up to 30 to 40% of children, which may lead to permanent disability.

More recently, the potential risk of a range of neurodevelopmental disorders in children born to fathers taking valproate in the three months before conception has been described and also the possibility of impaired fertility reproductive toxicity in males taking valproate.

These effects have led to a number of restrictions and regulatory requirements for the use of valproate.

In the majority of patients, there will be alternative treatment options to valproate, but in certain indications or where no other treatment is effective or tolerated it may be necessary to start or continue valproate.

The guidance in this section should be followed to ensure the regulatory requirements are met when prescribing and dispensing valproate.

Clinical guidelines relating to valproate use

Epilepsy

Bipolar Affective disorder

Migraine

Valproate safety measures

Valproate must NOT be started in new patients (male or female) younger than 55 years unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply.
Valproate must NOT be used in ANY females of child bearing potential unless there is a Pregnancy Prevention Programme (PPP) in place.

Female children receiving valproate who have not yet reached menarche do NOT need to fulfil the conditions of PPP, but they and their responsible person (parent / caregivers) need to be aware of the importance of the risks relating to exposure to valproate during pregnancy. The patient or responsible person must also be asked to contact their GP at menarche to ensure referral to the specialist team.

The following resources should be used to ensure the regulatory requirements are met and that patients are fully informed of the risks of valproate use dependent on age, gender and diagnosis.

FEMALE patients UNDER 55 years

MALE patients UNDER 55 years

MALE and FEMALE patients OVER 55 years

MHRA Drug Safety Update: Valproate: updated safety and educational materials to support patient discussion on reproductive risks

  • This summaries the advice for healthcare professionals prescribing valproate-containing medicines and provides a collection of safety and educational materials for patients and health care professionals.
  • These materials support the implementation of the PPP and clarify the roles and responsibilities of each health care professional.

The collection includes:

Roles and responsibilities of HCPs

 

Females of child bearing potential already prescribed valproate

 Females under 55 years newly starting valproate Males under 55 years newly starting valproate
Specialist Teams

Annual review with a specialist prescriber and completion of the annual risk acknowledgement form.

Explain the need to comply with effective contraception throughout treatment and for pregnancy testing when required.

 

Discuss risks, provide the patient guide for female patients and complete the annual risk acknowledgement form at initiation and at each annual review.

Pregnancy should be excluded before initiation and the need for effective contraception throughout treatment explained to female patients

Discuss risks, provide the patient guide for male patients and complete the male risk acknowledgement form on initiation only.

As a precautionary measure discuss that male patients and female partners should consider using effective contraception while using valproate and for at least 3 months after stopping

At the next review a second independent specialist prescriber should consider and agree that there is no other effective or tolerated treatment or that there are compelling reasons that the reproductive risks of valproate do not apply. Subsequent annual reviews only need one specialist signature unless the patient’s circumstances change

 On initiation a second independent specialist prescriber should consider and agree that there is no other effective or tolerated treatment unless there are compelling reasons that the reproductive risks do not apply. Subsequent annual reviews only need one specialist signature unless the patient’s circumstances change On initiation a second independent specialist prescriber should consider and agree that there is no other effective or tolerated treatment unless there are compelling reasons that the reproductive risks do not apply. Ongoing annual reviews are not required for males

Completed risk acknowledgement forms should be filed in the patient’s notes. A copy should also be sent to the patient and their GP. Until such time there is an electronic solution, forms should be manually uploaded to the patient’s SCI record.
General Practitioners

Review the new measures and the safety and educational materials, integrating them into clinical practice when referring patients and prescribing or dispensing valproate.
Refer patients to the relevant speciality if they have not received the appropriate follow up, do not have the relevant risk acknowledgement form in place or if they are considering planning a family.

Note: Inputting the Read code: #9KE.00 on 'Receipt of Risk' forms will enable the STU (Scottish Therapeutics Utility) search to track when follow-up is due.

Ensure patients have a received the appropriate patient guide and understand the requirements for effective contraception throughout treatment. Advise patients not to stop taking valproate without advice from a specialist.

Hospital pharmacies

Community pharmacies

Dispensing Practices


 

Display the pharmacy poster in a visible place in the pharmacy.
At each dispensing of valproate:

  • Detach the patient card from the carton and give this to the patient
  • Ensure the package leaflet is provided
  • Ensure a patient guide has been provided or that the patient knows they can access this via the QR code on the package leaflet
  • Unless there are exceptional circumstances valproate-containing medicines must always be dispensed in the manufacturer’s original full pack. If a different packaging is required a risk assessment should be completed (see section below)

Pharmacists should confirm with patients that they are aware of the risks associated with valproate use and that the appropriate safety measures are in place.

  • Refer patients to the GP if any safety measures are not in place or if pregnancy is suspected.
  • Advise patients not to stop taking valproate without advice from a specialist.

Full pack dispensing requirements

Unless there are exceptional circumstances, valproate-containing medicines MUST ALWAYS be dispensed in the manufacturer’s original full pack.

The manufacturer's original full pack for valproate-containing medicines includes specific warnings and pictograms, including a patient card and the package patient information leaflet. These documents alert patients to the risks to unborn babies if valproate is used in pregnancy.

The quantity prescribed can be rounded up or down to ensure patients receive valproate containing medicine in the manufacturer’s original packaging. Pharmacies / dispensing practices will be reimbursed without the need for additional endorsement.

The manufacturer’s original full pack does not have to be supplied where a risk assessment is in place that refers to the need for the patient to be supplied valproate-containing medicines in different packaging e.g. in a monitored dosage system or limited dispensing quantities. A patient card and package leaflet MUST be provided at each dispensing of valproate. 

For further details see the MHRA: Full pack dispensing of valproate-containing medicines - GOV.UK

Process for signatories

Valproate should NOT be initiated in patients aged under 55 years, unless two specialist prescribers experienced in the management of epilepsy or bipolar disorder independently consider and document that other treatments are not effective or tolerated.
  • The responsibility for obtaining a second specialist opinion lies with the specialist prescriber reviewing the patient and recommending valproate
  • The Commission of Human Medicines (CHM) advised that the second specialist signatory could include the following roles, however it is noted that this determination should be made at a local level:
    • Consultant adult or paediatric neurologists
    • Consultant psychiatrists
    • Speciality and associate specialist doctors in psychiatry and neurology
    • Paediatrician with special interest in epilepsy
    • Paediatrician who regularly manages complex epilepsy or bipolar disorder
    • Epilepsy nurse consultant
    • Specialist nurses in relevant disciplines
    • Specialist pharmacists
  • Discussion of cases at multidisciplinary team (MDT) meetings can substitute for the second signature, through a named representation of the MDT who should be a specialist prescriber. Although it is recommended that the countersigning specialist is NOT under the direct line management of the primary signatory.
  • There is no expectation that the countersigning specialist reviews the patient in person, however, they must have full access to all medical records and test results to be able to independently consider and document that there is no other effective or tolerated treatment. The countersigning specialist may want to contact the patient independently to ensure that they are adequately informed of risks and are consenting to treatment.
  • In the event the countersigning specialist disagrees with the decision to prescribe valproate, the case should be escalated to the appropriate clinical director for further discussion.

Contraception

Female patients of childbearing potential taking valproate should use effective contraception without interruption during the entire duration of treatment.

At least one effective method of contraception, preferably a highly effective user-independent form, such as an intra-uterine device or implant, or two complementary forms of contraception, including a barrier method, should be used.

As a precautionary measure it is recommended that men and their female sexual partners use effective contraception during valproate treatment and for at least three months after discontinuation.

Males should also be advised NOT to donate sperm whilst taking valproate and for three months after discontinuation of treatment.

Individual circumstances should be evaluated when considering the most appropriate contraception method, involving the patient in the discussion to support engagement and compliance.

There are a number of resources available to help guide these choices:

Pregnancy

Unless there is an absence of risk, pregnancy should be excluded by means of a negative pregnancy test before new female patients start treatment with valproate and again during treatment if there is any reason to suggest pregnancy or a lack of compliance with contraception.

It is important that patients prescribed valproate are advised not to become pregnant until discussing treatment options with a specialist.

If a patient taking an anti-epileptic drug (AED) is pregnant, then they should be advised not to stop taking their medication but to be urgently referred to their specialist for advice.

  • For migraine prophylaxis (unlicensed) and bipolar disorder, the MHRA advises that valproate medicines must NOT be used in pregnancy.
  • For epilepsy, the MHRA advises valproate must NOT be used in pregnancy unless two specialists independently consider and document that there is no other effective or tolerated treatment. If valproate is to be used, the lowest effective dose should be prescribed in divided doses to be taken throughout the day; modified-release preparations may be preferable to avoid high peak plasma-valproate concentrations. There is no dose threshold considered to be without any risk, however, the risk of birth defects and neurodevelopmental disorders is greater at higher doses.
Being prescribed anti-epileptic medication is a risk factor for conceiving a child with a neural tube defect and it is recommended that folic acid 5mg is taken before and during the pregnancy, until the twelfth week.

Specialist prenatal advice and monitoring should be sought when valproate has been taken in pregnancy.

Patient information

Patient information

Decision support tools

Valproate information

Pregnancy

Editorial Information

Last reviewed: 26/02/2026

Next review date: 28/02/2029

Author(s): Mental Health.

Version: 1

Co-Author(s): Learning Disabilities, Neurology, Rehabilitative Medicine, Paediatrics.

Approved By: TAM subgroup of the ADTC

Reviewer name(s): Ms R McLelland, Principal Pharmacist, Mental Health & Learning Disabilities.

Document Id: F399