According to a BBC report approximately 20,000 children have developed foetal valproate syndrome since the 1970s. Many parents have claimed that they were not made aware of the risks of valproate exposure to their unborn child during pregnancy. This is in spite of safety warnings that were introduced in 2016. For more awareness, in April 2018 the MHRA Drug Safety Update provided more comprehensive guidance on the use of valproate in females.
Valproate is commonly indicated for the treatment of epilepsy and bipolar. Medicine containing valproate can cause serious harm if taken during pregnancy.
The risks include a 10% chance of birth defects and a 30 to 40% chance of development problems that can cause learning disabilities.
Due to these risks, the MHRA has enforced that the use of valproate in women and girls of childbearing potential is contraindicated unless the conditions of a Pregnancy Prevention Programme are fulfilled. This includes premenopausal women unless their prescriber knows of convincing reasons that indicate there is no risk of pregnancy.
Valproate should not be used unless other treatments are ineffective or intolerable. The same principle applies in pregnancy for epilepsy, however its use in pregnancy for bipolar is contraindicated. Valproate is used off label, for example in migraine prophylaxis but regardless of its indication the same conditions included in a Pregnancy Prevention Programme must be fulfilled.
Epilim and Depakote are the most common brands of valproate dispensed in the UK. By September 2018 a warning symbol will be added to the packaging of valproate containing medicine. It will include a visual of a pregnant woman within a red circle with a line through it, to emphasise the teratogenicity risk. Pharmacists are encouraged to dispense in original packaging, to ensure that patients will always see the associated warning symbol. However if a carton must be split, warning stickers should be added to the box as well as a copy of the package leaflet. Another change may include smaller pack sizes to encourage closer monitoring i.e. monthly prescriptions.
A patient guide should be provided to women of childbearing potential and girls of any age who are initiating or continuing treatment with valproate. Pharmacists should supply a patient card each time valproate is dispensed to female patients to inform them of the risks. By December 2018 packs of valproate will be available with a detachable patient card.
An annual risk acknowledgement form must be agreed and signed by a specialist and patient/parent. A copy should be retained by the specialist and the patient/parent, as well as their GP. As a part of the Pregnancy Prevention Programme specialists must review girls and women at least annually, to re-evaluate treatment. A specialist prescriber is a consultant psychiatrist or a consultant neurologist.
Upon initiation of the Pregnancy Prevention Programme, pregnancy should be excluded by a serum pregnancy test before the first prescription of valproate is issued. Highly effective contraception must be arranged and maintained throughout valproate treatment. Pregnancy tests may need to be repeated through treatment if there are any reasons to suggest lack of compliance or contraceptive ineffectiveness.
Highly effective contraceptives are methods such a copper intrauterine device, levonorgestrel intrauterine system or progestogen-only implant. Use of condoms, combined or progestogen only contraceptive pills alone are not sufficient.
Patients should be informed to contact their GPs immediately for an urgent treatment review if they wish to become pregnant or suspect that they are already pregnant. This could result in more stringent monitoring around valproate during their pregnancy or a switch to another drug.
In conclusion, pharmacists should remind patients of the risk of valproate in pregnancy and emphasis the importance of contraception use. They should always be provided with the necessary supporting documentation. Patients should be encouraged to continue treatment without any disruptions. Pharmacists should also be aware of circumstances that require GP referral. Since this MHRA update is a fairly recent one, pharmacists should ensure that they speak to their patients about their knowledge of the Pregnancy Prevention Programme. Collaborative work with other healthcare professionals is necessary to educate and support patients with valproate therapy, in what might be a distressing time for them.
Epilepsy drug disabilities a ‘scandal’. BBC News. 2018. Available from: https://www.bbc.co.uk/news/uk-england-london-42717083
Valproate medicines (Epilim, Depakote): contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met [Internet]. GOV.UK. 2018. Available from: https://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#new-regulatory-measures-for-valproate-medicines