Pregabalin in pregnancy

Pregabalin (Lyrica): findings of safety study on risks during pregnancy

Advice for healthcare professionals:

• an observational study* of more than 2,700 pregnancies exposed to pregabalin has shown use in the first trimester to be associated with a slightly increased risk of major congenital malformations compared with exposure to no antiepileptic drugs or to lamotrigine or to duloxetine
• continue to provide counselling to patients using pregabalin on:
  • the potential risks to an unborn baby (see separate patient safety leaflet)
  • the need to use effective contraception during treatment
• continue to avoid use of pregabalin during pregnancy unless clearly necessary and only if the benefit to the patient clearly outweighs the potential risk to the fetus – ensure the patient has a full understanding of the benefits, risks, and alternatives, and is part of the decision-making process
• advise patients planning a pregnancy or who become pregnant during treatment to make an appointment to discuss their health condition and any medicines they are taking
• in cases where the benefit outweighs the risk, and it is clearly necessary that pregabalin should be used during pregnancy, it is recommended to:
  • use the lowest effective dose
  • report any suspected adverse drug reactions, including for the baby, via the Yellow Card scheme

Reminder for prescribers of ANY antiepileptic drug:

• at initiation and as part of the recommended annual review for patients with epilepsy, discuss the risks associated with antiepileptic drugs and with untreated epilepsy during pregnancy and review their treatment according to clinical condition and circumstances – see advice for antiepileptic drugs in pregnancy
• urgently refer anyone planning a pregnancy or who is suspected to be pregnant for specialist advice on their antiepileptic treatment
• if a patient is planning to have a baby, offer 5mg per day of folic acid before any possibility of pregnancy

* Detailed information on study and outcomes data

Study design and population

• Pregabalin pregnancy outcomes study (2)
  • was a population-based cohort study
  • used data from national administrative registries from 4 Nordic countries (Denmark, Finland, Norway, and Sweden) to characterise pregnancy outcomes
  • examined use of pregabalin in all authorised indications
    • prevalence of usage for each indication of pregabalin differed between the countries, but (where recorded) it was most commonly prescribed for anxiety and neuropathic pain - thought to be similar to the clinical situation in the UK
  • exposure data from the study indicated that the proportion of women using pregabalin in pregnancy had increased over the 10-year period (up to 2015/2016) and that exposure to pregabalin in pregnancy was most frequent in the first trimester
  • aimed to estimate the risk of major congenital malformations, other birth outcomes, and selected neurodevelopmental postnatal outcomes for babies who were exposed to pregabalin in-utero
  • aimed to collect this information for babies exposed to an alternative medicine for epilepsy (lamotrigine) and an alternative medicine for neuropathic pain and generalised anxiety disorder (duloxetine)
    • outcomes were also compared to babies not exposed to pregabalin or another antiepileptic drug (the comparison population)
• Study results:
  • showed a higher prevalence of major congenital malformations in the babies (live or stillborn) exposed to pregabalin in the first trimester of pregnancy (crude percentage 5.9%) compared with those not exposed to pregabalin or any other antiepileptic drug (crude percentage 4.1%)
    • after adjustment, the risk of major congenital malformations was slightly higher but not statistically significant with pregabalin monotherapy use in the first trimester versus the comparison group (adjusted prevalence ratio 1.14 (95% confidence interval (95% CI) 0.96 to 1.35))
    • data suggested modest but statistically significantly increased risks (less than 2-times) of major congenital malformations in pregnancies exposed to pregabalin compared with pregnancies exposed to lamotrigine or duloxetine
      • adjusted prevalence ratios for congenital malformations with first-trimester pregabalin monotherapy were 1.29 (95% CI 1.01 to 1.65) versus lamotrigine and 1.39 (1.07 to 1.82) versus duloxetine
    • slightly higher risks of specific malformations of the nervous system, eye, face (orofacial clefts), urinary system, and genitals were observed in babies exposed to pregabalin compared with those exposed to the other medicines or in the comparison population
      • however, estimates may be imprecise due to the low number of cases (1)
      • effects on the central nervous system and eye defects have also been observed in animals in preclinical studies
  • is noted that the prevalence of major congenital malformations in the comparison group (not exposed to any antiepileptic drug during the first trimester) was higher than the estimated prevalence in the UK general population (2-3%)
    • may be due to differences between the Nordic registries and UK studies in how they measure and categorise congenital malformations
    • may also possibly reflect improved diagnoses of these conditions over the study period

Reference:

1. Drug Safety Update volume 15, issue 9: April 2022: 1.
2. Toft G, and others. Pregabalin A0081359 Non-Interventional Final Study Report Abstract (Accessed April 20th 2022)