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European Union and the United Kingdom: Information about the risks of taking valproate medicines during pregnancy and new measures to avoid valproate exposure in pregnancy endorsed: Member State representatives agree new restrictions and pregnancy prevention programme

The European Medicines Agency (EMA) and Medicines and Healthcare products Regulatory Agency (MHRA) announce that the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) has endorsed new measures to avoid exposure of babies to valproate medicines in the womb, because exposed babies are at high risk of malformations and developmental problems.

Valproate-containing medicines have been approved to treat epilepsy and bipolar disorder and in some countries for prevention of migraine. In March 2018 the CMDh endorsed a strengthened regulatory position on valproate medicines. Valproate must no longer be used in any woman or girl able to have children unless she has a pregnancy prevention programme in place. This is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant.

If valproate is taken during pregnancy, up to 4 in 10 babies are at risk of developmental disorders (such as memory problems, lower intelligence than other children of the same age), and approximately 1 in 10 are at risk of birth defects (such as spina bifida, malformations of the limbs, heart, kidney, urinary tract and sexual organs). Children exposed to valproate in the womb are more likely to have autism, autistic spectrum disorders or attention deficit hyperactivity disorder (ADHD).

The new measures include a ban on the use of such medicines for migraine or bipolar disorder during pregnancy, and a ban on treating epilepsy during pregnancy unless there is no other effective treatment available.

Further, the medicines must not be used in any woman or girl able to have children unless the conditions of a new pregnancy prevention programme are met. The programme is designed to ensure that patients are made fully aware of the risks and the need to avoid becoming pregnant.

A visual warning of the pregnancy risks (in the form of boxed text with other possible elements such as a warning symbol) must also be placed on the packaging of the medicines and warnings be included on patient cards attached to the box and supplied with the medicine each time it is dispensed.

The CMDh agreed with EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), which carried out a review and recommended the new measures, that despite previous recommendations aimed at better informing patients of the risks with these medicines, women were still not always receiving the right information in a timely manner. The new measures endorsed by CMDh therefore strengthen previous restrictions on valproate use and requirements to inform women of the risk.

Companies marketing these medicines are also required to carry out additional studies on the nature and extent of the risks and to monitor valproate use and the long-term effects from affected pregnancies.

Because the CMDh position was agreed by majority vote it will now be sent to the European Commission, which will take a final legally binding decision valid across the EU.

Please refer to the following websites in EMA and MHRA for details:

MHRA:http://www.gov.uk/guidance/valproate-use-by-women-and-girls

EMA:http://www.ema.europa.eu/../news_detail_002929.jsp&mid=WC0b01ac058004d5c1

In Hong Kong, there are 12 registered pharmaceutical products containing valproic acid and/or valproate, and all products are prescription-only medicines. In Dec 2014, the Registration Committee of the Pharmacy and Poisons Board discussed the findings of an EMA’s previous review on the risks of valproate products in pregnancy and had decided that warnings and precautions on the risks of pregnancy should be included in valporate products. So far, the Department of Health (DH) has received 8 cases of adverse drug reaction in connection with valproic acid or valproate, but none of them was related to adverse effects in new-born babies whose mothers took valproate for their medical conditions.

Related news was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 14 Jul 2014, with the latest update posted on 16 Mar 2018. Letters to local healthcare professionals to draw their attention to the EMA recommendation were also issued on 12 Feb 2018. Furthermore, all registered pharmaceutical products containing valproic acid and/or valproate have already updated the relevant safety information of risks of valproate products in pregnancy in the sales packs and/or package inserts. DH will remain vigilant on the development of the issue and safety update of the drug issued by other overseas drug regulatory authorities.

Ends/Saturday, March 24, 2018
Issued at HKT 12:30

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