Guidance

Full pack dispensing of valproate-containing medicines

Published 11 October 2023

This is guidance for dispensing of valproate-containing medicines in the manufacturer’s original full pack, following amendments to the Human Medicines Regulations (HMRs). These amendments currently apply in England, Scotland and Wales. This guidance should be regarded as good practice by pharmacists in Northern Ireland.

Information for patients and the public about valproate 

Valproate is a treatment for epilepsy and bipolar disorder. Valproate-containing medicines are sodium valproate, valproic acid and valproate semisodium, so you may see these words on the box. Products may also be referred to using various brand names which include Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell.

It is very important that you do not stop taking valproate without advice from a healthcare professional. If you are concerned about the risks of valproate, talk to your doctor, pharmacist or another healthcare professional. 

There is a significant risk of birth defects for unborn babies and developmental disorders in children born to women who take valproate-containing medicines during pregnancy. Because of these risks, women and girls of childbearing potential must fulfil the conditions of the Valproate Pregnancy Prevention Programme which is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant. For more information about the risks of valproate-containing medicines in pregnancy see the The Medicines and Healthcare products Regulatory Agency (MHRA)’s Valproate use in women and girls page.

The manufacturers’ original full pack for valproate-containing medicines includes specific warnings and pictograms, including a patient card and the Patient Information Leaflet. These documents alert patients to the risks to unborn babies if valproate is used in pregnancy.

Some patients were previously not given their valproate-containing medicine in the manufacturer’s original full pack because the prescribed amount of medicine was different to the amount in the full pack. As a result the pharmacist had to give the exact amount of medicine in different packaging. This means that the patient didn’t always receive all of the information about the risks of valproate-containing medicines to an unborn baby.

Changes have been made to legislation in England, Scotland, and Wales to make sure that all patients (male and female) receive their valproate-containing medicine in the manufacturer’s original full pack and therefore will always receive information on the risks to the unborn child. Pharmacists must give valproate-containing medicines in the manufacturer’s original full pack every time, and the amount given must be as close as possible to the amount on the prescription. This applies to both NHS and private prescriptions.

In rare cases, pharmacists can make an exception to the requirement to dispense valproate-containing medicines in the manufacturer’s original full pack on an individual patient basis. This can only happen where a risk assessment is in place that refers to the need for different packaging. For example, the patient may need a monitored dosage system. In these exceptional cases, the pharmacist must ensure that the patient is given the Patient Information Leaflet which contains information about the risks of valproate-containing medicine for the unborn child. If this happens to you, your pharmacist can explain why you are not receiving manufacturer’s original full pack. These measures apply to all licensed valproate-containing medicines.

Information for healthcare professionals and organisations 

Background 

Following a consultation, the Government has put in place amendments to the Human Medicines Regulations 2012 (HMRs) to:

• require manufacturer’s original full pack dispensing of valproate-containing medicines
• enable pharmacists to supply up to 10% more than or less than the amount on a prescription of medicines other than those containing valproate, so that they can dispense a manufacturer’s original full pack instead of splitting the pack, known as original pack dispensing (OPD).

This guidance provides information on the reasons for the change to dispensing of valproate-containing medicines (as a above), and outlines what pharmacists need to do differently.

The change comes into force in England, Scotland and Wales from 11 October 2023. The legislative changes outlined above currently do not apply to Northern Ireland. This guidance on dispensing valproate-containing medicines should be considered by pharmacists in Northern Ireland as good practice. 

This MHRA guidance relates to valproate-containing medicines only. OPD legislation relates to all other medicines. Further guidance on amendments for OPD are being brought in after discussion between The Department of Health and Social Care (DHSC) and appropriate community pharmacy representative bodies on how the arrangements will apply.

Information about valproate-containing medicines

Valproate-containing medicines are used in epilepsy and bipolar disorder. There are known risks associated with valproate-containing medicines, including significant risks to children of mothers who took a valproate-containing medicine during pregnancy. Exposure of an unborn baby to valproate during pregnancy is associated with a high risk of congenital malformations (11%) and neurodevelopmental disorders (30–40%), which may lead to permanent disability. 

For more information about valproate risks in pregnancy see the MHRA’s Valproate use in women and girls page.

Why the rules on dispensing valproate-containing medicines have been changed

The aim of amendments to require manufacturer’s original full pack dispensing of valproate-containing medicines is to ensure that women always receive information about the harms of valproate during pregnancy. This will further decrease the number of babies who are exposed to valproate in pregnancy.

In 2018, a review by the MHRA into the harms of valproate-containing medicines use in pregnancy led to the introduction of the Valproate Pregnancy Prevention Programme as a condition of prescribing and dispensing valproate-containing medicines to women of childbearing potential.

To support these measures, the MHRA asked manufacturers to produce smaller pack sizes of valproate-containing medicines to encourage monthly prescribing and add a pictorial warning about the risks in pregnancy to the labelling of the original packs. Pharmacies were asked to dispense valproate-containing medicines in the original pack where possible and were provided with stickered warnings to add to the outer box if repackaging could not be avoided, due to the prescribed number of medicine doses (tablets, liquids, and ampoules). 

However, some patients and patient groups have continued to raise concerns that warnings were not always being provided to patients, and evidence continues to emerge suggesting that women are unaware of the significant risks posed to their unborn baby should they become pregnant while taking valproate-containing medicine. 

This new legislative amendment, requiring the supply of valproate-containing medicines in the manufacturer’s original full packaging, is a further measure to ensure that patients taking valproate-containing medicines have access to information setting out the risks and need for patients of childbearing potential to fulfil the conditions of the Pregnancy Prevention Programme before taking valproate-containing medicine.

The change in practice will ensure that patients (male and female) are provided with the specific warnings and pictograms on the labelling and a detachable patient card, along with the statutory Patient Information Leaflet and an additional patient booklet, which highlights the risks of taking the medicine while pregnant.

Your role and responsibility as a pharmacist, under the new legislation 

Unless there are exceptional circumstances, valproate-containing medicines must always be dispensed in the manufacturer’s original full pack from 11 October 2023. You must either round up or down so that the patient receives their supply in the manufacturer’s original full pack and ensure that they receive an amount that is as close as possible to that prescribed. You must not subsequently re-package any valproate-containing medicine into plain dispensing packaging.

This will ensure that all the safety warnings associated with taking valproate-containing medicine are clearly visible and available to patients. Providing the manufacturer’s original full pack with instructions about the safe and effective use of a product is an important patient safety measure. 

Exceptional circumstances

The manufacturer’s original full pack does not have to be supplied where:

(i) a risk assessment is in place that refers to the need for the patient to be sold or supplied valproate-containing medicines in different packaging from its manufacturer’s original full outer packaging (for example, in a monitored dosage system) and

(ii) assuming that the product is authorised, there are processes in place to make sure that the patient receives the Patient Information Leaflet. That is not the case for unauthorised medicines, unless they are only unauthorised as a result of an assembly process.

See example risk assessment from the National Pharmacy Association (login required).

Further information

No one should stop taking valproate without advice from their healthcare professional.

If patients are concerned about the reproductive risks of valproate-containing medicines, they should discuss this with their doctor, pharmacist, or another healthcare professional.

The MHRA keeps the safety of all medicines under continuous review and will take action when necessary to protect patients.

Reimbursement arrangements for this change to dispensing of valproate-containing medicines is dealt with by each devolved administration as part of their local NHS pharmaceutical service arrangements in their territory. This is outside the scope of MHRA guidance.

For England and Wales, further guidance on reimbursement for valproate-containing medicines is available in Clause 10B, Part II of the Drug Tariff.

The new legislation also applies to private prescriptions of valproate-containing medicines.

Queries about the content of this guidance

If you have any queries or comments about this guidance, please email SafetyAlerts@mhra.gov.uk and include the reference: “valproate full pack dispensing guidance”.