In 2014, the European Medicines Agency recommended that warnings on valproate medicines should be strengthened due to the risk of malformations and developmental problems in babies exposed to the drug in the womb.
However, the recommendation did not have a significant impact on prescribing of valproate. Many women reported that they were still not receiving sufficient information to make an informed decision.
Medicines containing valproate are contraindicated in pregnancy for migraine and bipolar disorder and should only be used in epilepsy if no other effective treatment options are available.
The recommendations have now been strengthened. Valproate medicines must no longer be used in women or girls of childbearing potential unless a Pregnancy Prevention Programme (PPP) is in place, and only then if other treatments are ineffective or not tolerated, as judged by an experienced specialist. These women should be advised on the use of effective contraception, and treatment should be started and supervised by a doctor experienced in epilepsy.
Valproate medicines must no longer be used in women or girls of childbearing potential unless a Pregnancy Prevention Programme is in place
The MHRA Safety Update (April 2018) highlights that practitioners should ensure that all women and girls (and carer, if necessary) on valproate are fully informed. Materials to help implementation include Patient and Healthcare Professional Guides (for GPs), Risk Acknowledgement Form (for pharmacists), patient cards and warning label stickers for dispensing cartons.
GPs should identify and recall all treated females of childbearing potential, provide them with a Patient Guide, check that they have been reviewed by a specialist in the last year and are on ‘highly effective’ contraception. Alternatively, two complementary forms of contraception may be used including a barrier method, and regular pregnancy testing should be considered.
Specialists must book annual review appointments with patients under the PPP and re-evaluate treatment as necessary. The pregnancy risks must be explained, and the Risk Acknowledgement Form re-signed with copies going to the patient or carer and the GP.
Whole packs of valproate medicines should be dispensed whenever possible. Packs dispensed to females of childbearing potential must have a warning label. By September 2018, a pregnant woman symbol in a red circle with a line through it, with warning text, will be printed on cartons.
Pharmacists should discuss pregnancy risks when dispensing valproate, ensure that patients have a Patient Guide and have seen their GP or specialist to discuss treatment and contraception.
European Medicine Agency. Valproate and Related Substances. 21/11/14
European Medicine Agency. New measures to avoid valproate exposure in pregnancy endorsed. 23/03/18
Medicines and Healthcare Products Regulatory Agency (MHRA). Drug Safety Update. Volume 11 issue 9; April 2018: 1.