Other safety alerts

The United Kingdom: Valproate medicines: contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met

Medicines and Healthcare products Regulatory Agency (MHRA) announces that valproate medicines must no longer be used in women or girls of childbearing potential unless a Pregnancy Prevention Programme is in place. This ensures all women and girls (and their parent, caregiver, or responsible person, if necessary) are fully informed of the risks and the need to avoid exposure to valproate medicines in pregnancy.

Valproate is highly teratogenic and evidence supports that use in pregnancy leads to physical birth defects in 10 in every 100 babies (compared with a background rate of 2 to 3 in 100) and neurodevelopmental disorders in approximately 30 to 40 in every 100 children born to mothers taking valproate. Due to the teratogenic risk, valproate medicines should not be used in girls and women of childbearing potential unless there is no suitable alternative as judged by a specialist experienced in the management of epilepsy or bipolar disorder.

Previous communications about the risk of neurodevelopmental disorders and the recommendation that women and girls of childbearing potential use effective contraception had little impact on prescribing. Data from the Clinical Practice and Research Datalink show that pregnancies continue to be exposed to valproate medicines. Additionally, patients have reported that they still are not receiving the necessary information to make an informed decision in many cases.

In Mar 2017, a EU scientific review examined the available evidence relating to the effectiveness of previous regulatory action and consulted widely with healthcare professionals and with patients. The review has now recommended new measures to avoid valproate exposure in pregnancy.

All women and girls of childbearing potential being treated with valproate medicines must be supported on a Pregnancy Prevention Programme. The Valproate Pregnancy Prevention Programme is supported by the following, which have been revised to be consistent with the new requirements:
- A Patient Guide – to be provided to girls (of any age) and women of childbearing potential (or their parent/caregiver/responsible person) who are started on or are continuing to use valproate medicines
- A Guide for Healthcare Professionals – for guidance to all prescribers, pharmacists, and other healthcare providers involved in the care of women and girls of childbearing potential using valproate medicines
- A Risk Acknowledgement Form – for the specialist and patient (or their parent/caregiver/responsible person) to sign at initiation and at treatment reviews at least every year. The patient should receive a copy of the form; one copy should be filed in the specialist notes, and one copy sent to the patient’s GP
- A Patient Card – to be given by pharmacists to all female patients who are dispensed valproate medicines to inform them of the risks
- Stickers with warning symbols – for pharmacists to add to the packaging of valproate medicines

The strengthened regulatory position includes a new absolute contraindication for use of valproate medicines in pregnancy for the bipolar disorder indication. In the epilepsy indication, the contraindication for use in pregnancy applies unless there are no suitable alternatives, recognising that in some patients who are already pregnant switching antiepileptic medicines may not be feasible. In this case, access to counselling about the risks should be provided and a Risk Acknowledgement Form signed by both specialist and patient.

Please refer to the following website in MHRA for details: http://www.gov.uk/drug-safety-update/valproate-medicines-epilim-depakote-contraindicated-in-women-and-girls-of-childbearing-potential-unless-conditions-of-pregnancy-prevention-programme-are-met

In Hong Kong, there are 12 registered pharmaceutical products containing valproic acid and/or valproate, and all products are prescription-only medicines. 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 13 Mar 2017, with the latest update posted on 24 Mar 2018. Letters to local healthcare professionals to draw their attention to the European Medicines Agency (EMA) recent review were also issued on 12 Feb 2018.

In Dec 2014, the Registration Committee of the Pharmacy and Poisons Board (Registration Committee) discussed the findings of an EMA 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. In light of the EMA recent review and the above MHRA announcement, the matter will be discussed by the Registration Committee and DH will remain vigilant on safety update of the drug issued by other overseas drug regulatory authorities.

Ends/Wednesday, Apr 25, 2018
Issued at HKT 16:00

Related Information:

European Union: PRAC assessing new data on potential risk of neurodevelopmental ... Posted 2025-07-12

Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronos... Posted 2025-06-11

The United Kingdom: Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epil... Posted 2025-06-11

Australia: Potential risk of neurodevelopmental disorders in children born to me... Posted 2025-03-07

The United Kingdom: Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epil... Posted 2025-02-14

The United Kingdom: MHRA instructs health organisations to prepare now for new m... Posted 2023-11-30

The United Kingdom: Valproate: reminder of current Pregnancy Prevention Programm... Posted 2022-12-13

Valproate: MHRA's reminder of current Pregnancy Prevention Programme requirement... Posted 2022-12-13

台灣：公告修訂含valproate類成分藥品用於婦女的使用原則 (Chinese only) Posted 2019-06-24

Singapore: Epilim® (valproate) – New restrictions on use Posted 2018-10-30

United Kingdom : Valproate Pregnancy Prevention Programme: actions required now ... Posted 2018-09-26