Published: 7 December 2023
Updated: 23 January 2024
Safety Information
Alert communication
Sodium valproate (Epilim) use in people who can father children: important new safety information
Update to original communication
7 December 2023
The Epilim data sheet and consumer medicines information leaflet have been recently updated with additional information about sodium valproate (Epilim) use in people who can father children. Educational resources are also being updated.
The additional information includes the following.
- Use of sodium valproate in people who can father children within the 3 months prior to conception may increase the risk of neurodevelopmental disorders in the child.
- The potential risks to children fathered more than 3 months (the time taken for new sperm to be formed) after stopping sodium valproate are unknown.
- If stopping sodium valproate, continue effective contraception for 3 months.
- Do not donate sperm while taking sodium valproate and for 3 months afterwards.
- Correction to the retrospective observational study results following reanalysis of one data set.
We have incorporated this additional information into the original communication below – see the bold text.
Please also refer to the Epilim data sheet and Dear Health Care Professional Letter (PDF, 179KB, 2 pages) for further information.
Original communication
30 May 2023A retrospective observational study suggests a potential increased risk of neurodevelopmental disorders in children whose fathers were treated with Epilim in the 3 months prior to the child’s conception compared to those treated with lamotrigine or levetiracetam. Epilim is the brand name for sodium valproate containing medicines in New Zealand.
The Epilim data sheet and consumer medicine information (CMI) leaflet have been updated with this important safety information. A Dear Healthcare Professional Letter (DCHP) has also been issued.
- Advice for consumers and caregivers
- Information for healthcare professionals
- Further information
- Useful links
Advice for consumers
- Keep taking your Epilim/sodium valproate as prescribed by your doctor.
- If you father a child while taking Epilim/sodium valproate in the 3 months prior to conception, it is possible the child may have impaired mental and/or motor development problems.
- Use effective contraception if you are starting or continuing on Epilim/sodium valproate treatment.
- If you are able to father children, speak with your doctor about the potential risks of taking Epilim/sodium valproate before and during conception, and your options if you wish to start a family.
- Avoid donating sperm while taking sodium valproate and for 3 months after stopping treatment.
Information for healthcare professionals
- The Epilim data sheet and CMI have been updated to include new safety information relating to use in males of reproductive potential.
- Use of sodium valproate within the 3 months prior to conception by people who are able to father children has been linked to a potential increased risk of neurodevelopmental disorders in children compared to those who took lamotrigine/levetiracetam.
- The potential risks to children fathered more than 3 months (the time taken for new sperm to be formed) after stopping sodium valproate are unknown.
- Inform patients of this potential risk and consider alternative treatment options for those wishing to father a child.
- Discuss the need for effective contraception when starting sodium valproate and periodically throughout treatment. If discontinuing treatment, continue effective contraception for 3 months.
- Inform patients to avoid donating sperm while taking sodium valproate and for 3 months after stopping treatment. The company has produced a guide which should be provided to all male patients of reproductive potential using sodium valproate.
Products affected
Epilim (sodium valproate) is indicated for the treatment of epilepsy and bipolar disorder.1
Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics is the New Zealand sponsor on behalf of Sanofi for all Epilim products in New Zealand.
| Product name | Strength |
|---|---|
| Epilim EC modified release tablet | 200 mg, 500 mg |
| Epilim Liquid oral solution | 200 mg/ 5 mL |
| Epilim 100 crushable tablet | 100 mg |
| Epilim IV Powder for injection with diluent | 100 mg/mL |
| Epilim Syrup | 200 mg/5mL |
Further information
A retrospective observational study of electronic medical records in 3 European Nordic countries suggested a potential increased risk of neurodevelopmental disorders in children after paternal exposure to sodium valproate in the 3 months prior to conception compared to those treated with lamotrigine or levetiracetam.
The study evaluated the association between paternal exposure to different anti-epileptic drugs at the time of conception and the risk of neurodevelopmental disorders.
The study identified a potential increased risk of neurodevelopment disorders in children (from 0 to 11 years old) born to males treated with sodium valproate at the time of conception, compared to those treated with lamotrigine or levetiracetam.
Across the 3 countries, the adjusted cumulative risk of neurodevelopmental disorders ranged from 4.0% to 5.6% (previous result: 5.6% to 6.3%) in the sodium valproate group versus 2.3% to 3.2% (previous result: 2.5% to 3.6%) in the composite lamotrigine/levetiracetam monotherapy exposure. The pooled adjusted hazard ratio for neurodevelopmental disorders overall, obtained from the meta-analysis of the 3 datasets, was 1.50 (95% CI: 1.09 – 2.07) (previous result: 1.47 (95% CI: 1.10–1.96). As a reminder, it is estimated that up to 30-40% of children whose mothers took valproate during pregnancy may have problems with early childhood development.
Due to study limitations, it was not possible to determine which of the studied neurodevelopmental subtypes (autism spectrum disorder, intellectual disability, communication disorder, attention deficit/hyperactivity disorder, movement disorders) contributed to the overall increased risk of neurodevelopmental disorders. Further investigations are needed.
Useful links
Consumers and caregivers:
- Sodium valproate male patient guide (Sanofi) (PDF 167KB, 2 pages)
- Epilim consumer medicines information
- Report an adverse reaction to a medicine
Health professionals:
- Dear Healthcare Professional letter (DHCP)
- Sodium valproate educational materials for healthcare professionals (Sanofi) (PDF 513KB, 15 pages)
- Sodium valproate male patient guide (Sanofi) (PDF 167KB, 2 pages)
- Epilim data sheet
- Report an adverse reaction to a medicine
View the original publication of this alert.
References
- Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2023. Epilim New Zealand data sheet November 2023. URL: medsafe.govt.nz/profs/Datasheet/e/Epilimtabsyrliqiv.pdf (accessed 6 December 2023).
