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MHRA tightens licence restrictions on valproate for women

Women and girls must be on the pregnancy prevention programme to be prescribed valproate

Louise Prime

Wednesday, 25 April 2018

Women and girls ‘of childbearing potential’ must not be prescribed valproate unless they are on the pregnancy prevention programme (PPP), the Medicines and Healthcare products Regulatory Agency has told doctors. It announced yesterday that it has changed the licence for valproate medicines (Epilim, Depakote and generic brands), which are used to treat epilepsy and bipolar disorder, because of their significant teratogenic potential. Its aim is to reduce to an absolute minimum the number of pregnancies exposed to valproate medicines and ensure that all women and girls are aware of the risks.

The MHRA said antenatal valproate exposure poses a significant risk to babies – up to four in 10 exposed babies are at risk of persistent developmental disorders, and about one in 10 are at risk of birth defects. As a result, it has told all women and girls currently taking valproate medicines to contact their GP to arrange a treatment review – but it emphasised that they must not stop taking their drugs without medical advice.

The MHRA told doctors that they must now make sure that any female patient for whom they intend to prescribe valproate is enrolled in the PPP, which includes the requirement for specialist review at least annually, and a risk acknowledgement signed by the patient. Further changes to support the licence change will include the introduction of smaller pack sizes to encourage monthly prescribing, and inclusion of a pictogram/warning image on valproate package labelling.

Other bodies will also be making changes to support the licence change. These include new alerts on GPs’ computer systems, to ensure that prescribing behaviour changes promptly; and, following collaboration between NHS Digital and suppliers of GP computer systems, a search and audit function to help to identify women and girls taking valproate, as well as updating valproate prescribing alerts.

The National Institute of Health and Care Excellence is fully updating its guideline on epilepsy, focusing particularly on areas where the new licence conflicts with current advice that names valproate as the drug of choice; and it is amending its other guidelines that mention valproate, to reflect the licence change.

Chair of the Royal College of GPs Professor Helen Stokes-Lampard said: “GPs are acutely aware of the risks associated with prescribing sodium valproate to women of childbearing age and we welcome this change in legislation as a logical way forward to help ensure our patients’ safety. However, any patients currently taking sodium valproate should not stop doing so without seeking expert medical advice.

“As a general rule, it is important that patients read and take heed of warnings on the packets of any medication they are taking – and that any woman on long-term medication speaks to their GP if they are planning to have a baby.”

The Faculty of Sexual and Reproductive Healthcare (FSRH) also welcomed the new regulatory changes because of the clear evidence on the significant risks from valproate medicines. FSRH president Dr Asha Kasliwal added: “Some of these drugs can affect how well some contraceptive methods work. However, women and girls who need these life-changing medications do not have to be left at risk for unplanned pregnancies. Our 2017 clinical guidance on drug interactions with hormonal contraception* recommends that women and girls taking sodium valproate use highly effective methods of contraception to avoid an unplanned pregnancy, both during treatment and for the recommended timeframe after discontinuation.

“Methods of contraception which are considered highly effective in this context include long-acting reversible contraceptives (LARCs) such as the copper IUD, levonorgestrel intrauterine system (LNG-IUS), the progestogen-only implant (IMP) and sterilisation. Women should seek advice from a specialist, who will carry out a pregnancy risk assessment and provide evidence-based advice on the most suitable method for them.”


*CEU Clinical Guidance: Drug Interactions with Hormonal Contraception. The Faculty of Sexual Health and Reproductive Healthcare, November 2017.

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