Sodium valproate in pregnancy

Sodium valproate in pregnancy

Valproate (Epilim, Depakote and other generic brands) is associated with a significant risk of birth defects and developmental disorders in children born to women who take valproate during pregnancy

• since 2018 any use of valproate in patients of childbearing potential has to be within the terms of the Pregnancy Prevention Programme (1,2) - is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant

Sodium valproate:

• is highly teratogenic and evidence supports a rate of congenital malformations of 10% in infants whose mothers took valproate during pregnancy and neurodevelopmental disorders in approximately 30% to 40% of children (1)
  • for this reason, valproate should not be used in girls and women of childbearing potential unless other treatments are ineffective or not tolerated, as judged by an experienced specialist
  • birth defects seen when mothers take valproate during pregnancy include (2):
    • spina bifida
    • facial and skull malformations (including cleft lip and palate)
    • malformations of the limbs, heart, kidney, urinary tract and sexual organs
    • in women who take valproate while pregnant, about 3–4 children in every 10 may have developmental problems, and these disorders can be seriously debilitating and permanent effects on development can include:
      • being late in learning to walk and talk
      • lower intelligence than other children of the same age
      • poor speech and language skills
      • memory problems
      • children exposed to valproate in the womb are more likely to have autism or autistm spectrum disorders is also some evidence children may be more likely to be at risk of developing symptoms of attention deficit hyperactivity disorder (ADHD)

Valproate should not be used in pregnancy (2)

• valproate must not be used in any woman or girl able to have children unless there is a Pregnancy Prevention Programme (PPP) in place - is designed to make sure patients are fully aware of the risks and the need to avoid becoming pregnant
• in 2018, a large-scale review of the safety of valproate led to regulatory changes intended to reduce the number of unborn babies exposed to valproate. These included a ban on the use of valproate for migraine or bipolar disorder during pregnancy, and a ban on the use of valproate to treat epilepsy during pregnancy unless no other effective treatment is available (3)
  • exposure to valproate in pregnancy is associated with physical birth defects in 11% of babies and neurodevelopmental disorders in up to 30-40% of children, which may lead to permanent disability

Advice for healthcare professionals (3):

• valproate must not be started in new patients (male or female) younger than 55 years, unless two specialists independently consider and document that there is no other effective or tolerated treatment, or there are compelling reasons that the reproductive risks do not apply. For the majority of patients, other effective treatment options are available
• at their next annual specialist review, women of childbearing potential and girls receiving valproate should be reviewed using the revised valproate Annual Risk Acknowledgement Form. A second specialist signature will be needed if the patient is to continue on valproate, however subsequent annual reviews will only require one specialist
• general practice and pharmacy teams should continue to prescribe and dispense valproate and if required offer patients a referral to a specialist to discuss their treatment options. Valproate should be dispensed in the manufacturer’s original full pack
• report suspected adverse drug reactions associated with valproate on a Yellow Card

The summary of product characteristics should be consulted before prescribing this drug.

Notes:

• valproate treatment must not be used in girls and women including in young girls below the age of puberty, unless alternative treatments are not suitable and unless the conditions of the pregnancy prevention programme are met
  • since 2018, valproate has been contraindicated in women of childbearing potential unless the conditions of the Pregnancy Prevention Programme (PPP) are followed (3)
• with respect to stopping valproate in bipolar disorder (4):
  • if stopping valproate, reduce the dose gradually over at least 4 weeks to minimise the risk of relapse

Reference:

1. MHRA (January 2021). Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review Drug Safety Update volume 14, issue 6: January 2021: 1.
2. MHRA (November 2023). Valproate use by women and girls - Information about the risks of taking valproate medicines during pregnancy
3. MHRA . Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell▼): new safety and educational materials to support regulatory measures in men and women under 55 years of age.Drug Safety Update volume 17, issue 6: January 2024: 1
4. NICE (April 2018). Bipolar disorder