Valproate: patient safety alerts and risks of exposure in pregnancy

Superintendent update focusing on valproate and risks of exposure in pregnancy

Dear Superintendent,

The high risks associated with the exposure to valproate during pregnancy remains a high priority patient safety concern of NHS Improvement, the Medicines and Healthcare products Regulatory Agency (MHRA) and health organisations across Europe. Valproate medicines (such as Epilim® and Episenta®), including valproate semisodium/valproic acid (Depakote®), are commonly prescribed for conditions such as epilepsy, bipolar disorder, migraine (off-label) and chronic pain (off-label), and the risk of developmental disorders and congenital malformations in children exposed to valproate in utero are well known.

Children exposed to valproate during pregnancy have up to a 40 per cent risk of a developmental disability and a 10 per cent risk of birth defects. The birth defects observed in children exposed to valproate in utero include spina bifida and malformations of the face, skull, limb, kidney and heart. Developmental disorders observed include late development in speech, lower intelligence and memory problems. Overall, 1 in 10 children exposed to valproate in utero will have a birth defect and 3-4 in 10 children will experience developmental issues.

Although the risks associated with in utero exposure to valproate are established and numerous patient safety communications to healthcare professionals have been circulated, many females continue to be prescribed valproate and remain unaware of the risks.

Between July 2016 and September 2016, NHS England identified over 17,800 females between the age of 14 and 45 were prescribed valproate in England, with 1 in 5 of these females unaware of the risks of use during pregnancy.

The MHRA advise that females, including children, adolescents, pregnant, or in those with childbearing potential are not prescribed valproate, unless other treatments are ineffective or not tolerated. For pregnant females or those of childbearing potential which require valproate treatment, it is essential that such patients are aware of the associated risks with valproate.

Valproate resources
A range of resources are available from the MHRA to support both healthcare professionals and patients, when prescribing, dispensing and using valproate.

Healthcare professional resources:

• “Important Information for Healthcare Professional on the Risks of Valproate in Female Patients”
• “Treatment with valproate for female patients: Checklist for patients and prescribers”

Patient resources:

• “Valproate Patient Guide”
• “Patient Card – Key Facts”

Valproate dispensing checklist
This valproate dispensing checklist is designed to support community pharmacists with all patient safety aspects when dispensing valproate for pregnant females or those of childbearing potential.

1. Develop a process to highlight valproate prescriptions for females, for example the use of alert stickers
2. Ensure the patient has been informed of and understands the risks associated with valproate use during pregnancy
3. Check if the patient has received a valproate patient card – these are available from the MHRA website or as additional risk materials in the Summary of Product Characteristics
4. Check the patient has read the information contained in the patient card, has signed and dated the card – this indicates their understanding of the information and reinforces accountability
5. Check if the female is using effective contraception – the Faculty of Sexual & Reproductive Healthcare (FSRH) state progesterone-only (PO) implants, PO injectables and intrauterine devices provide the best protection
6. Remind the patient not to stop treatment and to seek medical advice when planning a pregnancy or if the female becomes pregnant
7. Where identified, address prescribing/prescriber issues – if there is evidence of inappropriate valproate prescribing or information has not been provided to the female about the risks of valproate in pregnancy, consult the prescriber – are they undertaking regular reviews? Are they aware of the recommendations and resources available? Are they using the prescriber checklist? If not, refer the prescriber to the MHRA resources
8. Where applicable, report any suspected adverse effects via the Yellow Card Scheme

Home country specific guidance
Patient safety alerts in regards to the use of valproate in females have been issued for all home countries in the UK:

• England: NHS Improvement
• Wales: Patient Safety Wales
• Scotland: Healthcare Improvement Scotland
• Northern Ireland: Safety Quality and Standards Circulars

For further information please contact the NPA Pharmacy Services team on 01727 891800 or email at:  pharmacyservices@npa.co.uk.