On 21 March 2018, the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) authorised new measures to avoid babies being exposed to valproate medicines in the womb, due to the high risk of malformations and developmental problems.¹

While medicines containing valproate have been approved nationally and within the EU to treat conditions such as epilepsy and bipolar disorder – and, in some countries, migraines – these new measures include a ban on the use of valproate during pregnancy.

For women or girls who are not pregnant, but are of child bearing age, valproate must not be prescribed unless all the Pregnancy Prevention Programme conditions – set by the Medicines and Healthcare products Regulatory Agency (MHRA) – are met.

The strict rules set out by the Pregnancy Prevention Programme ensure female patients taking valproate medicines²:

• have been told and understand the risks of use in pregnancy and have signed a Risk Acknowledgement Form
• are on highly effective contraception if necessary
• see their specialist at least every year.

But what happens if a patient already taking a valproate medicine comes for another prescription and doesn’t meet one of the above criteria?

MAKING A JUDGMENT CALL

If a patient’s medication is stopped abruptly, it can present a health risk. But if a doctor were to prescribe outside the Pregnancy Prevention Programme it could present a medicolegal risk, and if the patient becomes pregnant, a potential risk to an unborn child.

There is no explicit guidance on how GPs should proceed in the event that an annual Risk Acknowledgement Form has not been completed, so you should exercise your own clinical judgment in applying the available professional guidelines, such as the GMC’s prescribing guidance.³

Where an annual review with a specialist has not been carried out in time, in accordance with the Pregnancy Prevention Programme, a GP would need to consider if it is justifiable to continue to prescribe valproate medication. For example, they should consider whether the risk to health of stopping the medication abruptly is deemed to be greater than the risk of temporarily continuing the medication. Once the decision has been made, it should be documented in the patient’s medical record, along with the rationale for it.

However, any such prescription should function only as a stop gap between the last annual review and the next available opportunity for the overdue review to be conducted. The prescription should be approached with due caution, both for the safety of the patient primarily, and to ensure that you are in a position to explain and justify a decision to continue prescribing valproate medicines.

The benefits and risks of the medication should be carefully reconsidered at regular treatment reviews. It may be a decade or more before harm emerges, and accurate, detailed and contemporaneous medical records are crucial. The MHRA has a comprehensive patient information booklet, which should be shared with the patient and clearly documented in the medical record.⁴

A thorough discussion should be had with the patient, where you detail the risks as noted in the Risk Acknowledgement Form, and explain that while a specialist would normally complete the form, in the current circumstances it is good practice for you – as the prescribing GP – to be assured of the patient’s awareness of the associated risks before any repeat prescription.

This discussion should be accurately documented in the patient’s notes. In this way, the purpose of the annual Risk Acknowledgement Form may still be fulfilled in lieu of the form being completed in due course.

It is also advisable for you to enquire as to why the specialist annual review has not taken place, and liaise with the patient and secondary care to ensure this required review is conducted as a matter of urgency where the review date has passed.

RAISING CONCERNS

If you are concerned that an issue has been caused by secondary care in not reviewing the patient when required,this should be raised via the appropriate channels – in the first instance, the secondary care provider itself and/or the local CCG, health board or trust.

It may also be appropriate to raise this concern via the Local Medical Committee if other local practices are experiencing similar difficulties. As above, efforts made to liaise with secondary care and local services should be well documented in the patient’s notes. The GMC’s guidance ‘Raising and acting on concerns about patient safety’ is a useful resource.⁵

Alternatively, if the patient(s) concerned have not attended their annual review, this should be urgently addressed directly with the patient, stressing the importance of attendance to their continued treatment and care.

REFERENCES

1. New measures to avoid valproate exposure in pregnancy endorsed | European Medicines Agency. Ema.europa.eu. 2019. ema.europa.eu/en/news/new-measuresavoid-valproate-exposure-pregnancy-endorsed (accessed 4 Feb 2019).
2. Valproate medicines (Epilim, Depakote): Pregnancy Prevention Programme materials online. GOV.UK. 2019. gov.uk/drug-safety-update/valproate-medicines-epilimdepakote-pregnancy-prevention-programme-materials-online (accessed 4 Feb 2019).
3. Good practice in prescribing and managing medicines and devices. Gmc-uk.org. 2019.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/prescribing-and-managing-medicines-and-devices (accessed 4 Feb 2019).
4. Patient Guide: What women and girls need to know about valproate. Medicines and Healthcare products Regulatory Agency 2018.
5. GMC. Raising and acting on concerns about patient safety. 2019. gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/raising-and-acting-on-concerns (accessed 4Feb 2019).