High risk medicines: valproate

Sodium valproate and valproic acid are known collectively as valproate.

Brands include Epilim, Depakote, Convulex, Episenta, Epival, Kentlim, Orlept, Syonell and Valpaland. There are other generic brands.

Valproate is licensed for use in epilepsy and bipolar disorder. It is also used off-label for depression, neuropathic pain, dementia and migraine.

Valproate and pregnancy

Taking valproate during pregnancy poses a significant risk of birth defects and developmental disorders.

Following several alerts, the Medicines and Healthcare products Regulatory Authority (MHRA) issued a drug safety update in April 2018.

Prevent - valproate pregnancy prevention programme

The MHRA update advises:

‘Valproate medicines must no longer be used in women or girls of childbearing potential unless a Pregnancy Prevention Programme is in place’.

The drug safety update said:

• All women and girls of childbearing potential being treated with valproate medicines must be supported on a Pregnancy Prevention Programme.
• This includes female patients who are not sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.
• Use of valproate in pregnancy is contraindicated for bipolar disorder and migraine prophylaxis. It must only be considered for epilepsy if there is no suitable alternative treatment.

Under the Pregnancy Prevention Programme, healthcare professionals are responsible for prescribing valproate safely:

GPs

GPs must:

• identify and review all female patients on valproate, including when it is used outside the licensed indications (off-label use) - for example migraine prophylaxis
• provide patient information materials every time the patients attend their appointments or receive their medicines
• check they have been reviewed by a specialist in the last year and are prescribed appropriate contraception

Specialists

Specialists must:

• book review appointments at least annually with women and girls under the Pregnancy Prevention Programme
• re-evaluate treatment as necessary
• explain clearly the conditions as outlined in the supporting materials
• complete and sign the valproate annual risk acknowledgement form
• provide copies of the form to the patient, carer or responsible person and send a copy to the GP

Pharmacists

Pharmacists must:

• ensure valproate medicines dispensed to women and girls of childbearing potential have a warning label
• discuss risks in pregnancy with female patients each time valproate medicines are dispensed
• make sure patients have the valproate patient guide and have seen their GP or specialist to discuss their treatment and the need for contraception

Contraception

At least one highly effective method of contraception or two complementary forms of contraception including a barrier method should be used.

Examples of highly effective contraception include:

• copper intrauterine device
• levonorgestrel intrauterine system
• progestogen-only contraceptive implant

User dependent methods include the condom, cap, diaphragm, oral contraceptive pill (COC) and fertility awareness based methods. These must be used together with a barrier method of contraception. Frequent pregnancy testing should be carried out.

Considerations for providers and staff

The pregnancy prevention programme applies to all women of childbearing potential taking a medicine containing valproate. The only exception is where the specialist considers there is no risk of pregnancy. For example, pre-menarche or post-menopausal.

The reasons for not enrolling on the programme should be recorded on the annual risk acknowledgement form. This should be signed by the woman.

Providers of adult social care and their staff should:

• identify women of childbearing potential who are taking valproate - you should not assume that a woman with a learning disability is not sexually active
• support women to attend their GP and/or specialist appointments for review
• work with healthcare professionals to provide information about the Pregnancy Prevention Programme - this should be in an accessible format where necessary, for example easy read
• hold a copy of the annual risk acknowledgement form if the woman is unable to
• proactively support women with their contraceptive needs, where necessary

If a pregnancy occurs, providers must support women to seek advice from a specialist as soon as possible.