Use of valproate during pregnancy
The Federal Office provides information on recommendations of the Committee for Risk Assessment and Pharmacovigilance (PRAC) within the framework of the European risk assessment procedure according to Article 31 of Directive 2001/83/EC regarding the use of valproate during pregnancy.
All these recommendations are to a large extent already currently included in the currently valid Austrian technical information and directions for use. These will be harmonized with the European wording after final completion of the procedure.
Measures at EU level:
Valproate is approved for the treatment of epilepsies as well as for the treatment of manic episodes in bipolar disorders. The use of valproate during pregnancy is associated with an increased risk of congenital malformations. Similarly, developmental disorders as well as autistic spectrum disorders have been reported.
Valproate should not be prescribed to pregnant women, or to girls and women of childbearing age, or should be prescribed only if alternative therapies are ineffective or not tolerated. In women of childbearing age, effective contraception must also be provided. Initiation of such therapy and its monitoring should be performed only by physicians familiar with the use of valproate.
In recent studies, developmental abnormalities such as delayed walking and speech, memory problems, and decreased intellectual abilities were observed in 30-40% of preschool children exposed to valproate in utero. In addition, children exposed in utero showed an 11% risk of congenital malformations (such as neural tube defects and cleft palate) compared with a 2-3% risk in the general population. Similarly, study results indicate that these children are at increased risk for autism spectrum disorder (approximately 3 times higher than in the normal population) and early childhood autism (approximately 5 times higher than in the normal population). There is also a possible increased risk of developing attention deficit hyperactivity disorder (ADHD).
The Pharmacovigilance Risk Committee (PRAC) therefore recommends that physicians and treated women be made aware of these risks in future with appropriate information material. It is recommended that prescribing physicians review any treatment with valproate of girls and women at regular intervals, especially in the case of pubescents and women who wish to become pregnant.
Situation in Austria
The following medicinal products are approved in Austria:
- Depakine chrono retard 300 mg film-coated tablets.
- Depakine chrono retard 500 mg film-coated tablets
- Depakine chronosphere 100 mg sustained-release granules in sachets
- Depakine Chronosphere 1000 mg sustained-release granules in sachets
- Depakine Chronosphere 50 mg sustained-release granules in sachets
- Depakine Chronosphere 250 mg sustained-release granules in sachets
- Depakine Chronosphere 500 mg sustained-release granules in sachets
- Depakine Chronosphere 750 mg sustained-release granules in sachets
- Convulex 150 mg - capsules
- Convulex 300 mg - capsules
- Convulex 500 mg - capsules
- Convulex 50 mg/ml - syrup for children
- Convulex 100 mg/ml - solution for injection
- Convulex 300 mg/ml - Oral solution
- Convulex 300 mg - sustained release tablets
- Convulex 500 mg - sustained release tablets
BASG currently has 4 reports of related adverse reactions from Austria.
Recommendations of the BASG
Recommendations for prescribers:
- Initiation of valproate therapy and its monitoring should be performed only by physicians familiar with the use of valproate.
- Valproate should not be prescribed to pregnant women or to girls and women of childbearing age, or should be prescribed only if alternative therapies are ineffective or not tolerated.
- Effective contraception must be provided for women of childbearing age.
- Physicians should review any treatment with valproate in girls and women at regular intervals, especially in pubertal girls and women who wish to become pregnant.
Recommendations for Patients:
- Under no circumstances should therapy with valproate be discontinued independently without consulting the treating physician.
Further information:
European Medicines Agency press release (10/10/2014):
Queries (technical): Dr. Christoph Baumgärtel, Tel: 050555/36004 Email: christoph.baumgaertel@ages.at Queries (for media): Communications Management, Tel.: 050555/25000 E-mail: presse@ages.at
