PRAC recommends strengthening the restrictions on the use of valproate in women and girls
The EMA’s Pharmacovigilance and Risk Assessment Committee (PRAC) recommends strengthening the restrictions on the use of the antiepileptic valproate due to the risk of malformations and developmental problems in children exposed to valproate in the womb.
In Denmark, valproate is authorised for the treatment of epilepsy and bipolar disorder. According to the new recommendations, valproate should not be used for the treatment of these indications in girls or women who are pregnant or can become pregnant, unless other treatments are ineffective or not tolerated. Women for whom valproate is considered the only treatment option should use effective contraception and treatment should be started and supervised by a specialist.
Women treated with valproate should not stop taking the medicine without first consulting their doctor.
Doctors prescribing valproate must inform women of the potential risks to support the decision about the treatment.
Recommendations based on new studies
PRAC's recommendations are based on a review of the available data on the effects of valproate exposure during pregnancy. PRAC also consulted patients and families who have experience in treatment with valproate as well as a group of specialists in this field.
New studies have shown a risk of developmental problems of up to 30% to 40% in pre-school children exposed to valproate in the womb. The development problems include delayed walking and talking, memory problems, difficulty with speech and language and lower intellectual ability.
The data also show that children exposed to valproate in the womb are at an approximately 11% risk of malformations at birth (such as neural tube defects and cleft palate) compared to a 2% to 3% risk for children in the general population. Available data show that children exposed to valproate in the womb are at increased risk of autistic spectrum disorder (around 3 times higher than in the general population) and childhood autism (5 times higher than in the general population). And limited data suggest that children exposed to valproate in the womb may be more likely to develop symptoms of attention deficit hyperactivity disorder (ADHD).
Educational material and information
PRAC recommends that educational material should be provided to all healthcare professionals and to women who are prescribed valproate to inform them of these risks. The product information for the medicine will also be updated.
The product information for valproate medicines available in Denmark includes information about the risks related to use of the medicine during pregnancy, but it will be further updated with the latest information and recommendations.
According to the Register of Medicinal Product Statistics, approximately 16,000 individuals in the primary sector were treated with valproate in 2013.
PRAC's recommendation will now be sent to the Co-ordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a final position. In the meantime, women currently taking valproate should consult their doctor if they have any questions about the treatment.