- lamotrigine and levetiracetam
- large amount of data exists for lamotrigine (more than 12,000 pregnancies exposed) and levetiracetam (more 1,800 pregnancies exposed) and these data do not suggest an increased risk of majorcongenital malformations when these antiepileptic drugs are used at the usual maintenance doses
- for lamotrigine, studies investigating the effect of dose have shown conflicting results; one study using data from EURAP showed a statistically significant increase in the rate of major congenital malformations when doses of lamotrigine higher than 325mg per day were compared with doses of lamotrigine 325mg per day or lower
Summary of key conclusions of review (1)
- Lamotrigine – Studies involving more than 12,000 pregnancies exposed to lamotrigine monotherapy consistently show that lamotrigine at maintenance doses is not associated with an increased risk of major congenital malformations
- Levetiracetam – Studies involving more than 1,800 pregnancies exposed to levetiracetam do not suggest an increased risk of major congenital malformations
- For both lamotrigine and levetiracetam, the data on neurodevelopmental outcomes are more limited than those for congenital malformations. The available studies do not suggest an increased risk of neurodevelopmental disorders or delay associated with in-utero exposure to either lamotrigine or levetiracetam; however, the data is inadequate to rule out definitively the possibility of an increased risk
- For the other key antiepileptic drugs, data show:
- an increased risk of major congenital malformations associated with carbamazepine, phenobarbital, phenytoin, and topiramate use during pregnancy
- the possibility of adverse effects on neurodevelopment of children exposed in utero to phenobarbital and phenytoin
- an increased risk of fetal growth restriction associated with phenobarbital, topiramate, and zonisamide use during pregnancy
Actions for prescribers (1)
- At initiation and as part of the recommended annual review for patients with epilepsy, specialists should discuss with women the risks associated with antiepileptic drugs and with untreated epilepsy during pregnancy and review their treatment according to their clinical condition and circumstances – we have produced a safety information leaflet to assist with this discussion
- Urgently refer women who are planning to become pregnant for specialist advice on their antiepileptic treatment
- All women using antiepileptic drugs who are planning to become pregnant should be offered 5mg per day of folic acid before any possibility of pregnancy
- For lamotrigine, levetiracetam or any antiepileptic drugs that can be used during pregnancy, it is recommended to
- use monotherapy whenever possible
- use the lowest effective dose (see below for key dose monitoring advice, including for lamotrigine and levetiracetam)
- report any suspected adverse effects experienced by the mother or baby to the Yellow Card scheme
Reminder of advice to give to women with epilepsy
- Do not stop taking antiepileptic drugs without discussing it with your doctor
- If you are taking an antiepileptic drug and think you may be pregnant, seek urgent medical advice, including urgent referral to your specialist
- Read the patient information leaflets that accompany your medicines and other information provided by your healthcare professional
Reference:
- MHRA(January 2021).Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review Drug Safety Update volume 14, issue 6: January 2021: 1.