The UK medicines regulator has warned that men taking valproate and their partners should use effective contraception, because of a small increased risk of harm to children if the drug is used by a father at conception.
Healthcare professionals should inform male patients about this ‘newly identified risk’ at their next routine treatment review and discuss how it impacts their current treatment and other options available, the Medicines and Healthcare products Regulatory Agency (MHRA) said.
It follows a retrospective observational study which found a possible association between valproate use by men and a small increased risk of a range of neurodevelopmental disorders in their children when compared to men prescribed lamotrigine or levetiracetam.
In the study of records from Scandinavian countries, researchers found around 5 out of 100 children had a neurodevelopmental disorder when born to fathers treated with valproate compared with around 3 out of 100 when born to fathers treated with lamotrigine or levetiracetam.
The MHRA first announced it would review the evidence of valproate in men and neurodevelopmental disorders in pregnancy in January this year.
It has already warned healthcare organisations to prepare for new tightened rules on prescribing valproate under which the epilepsy drug must not be started in new patients – male or female – under the age of 55 unless two specialists have agreed and documented that there are no other effective or tolerated treatments.
The new updated advice was a ‘precautionary measure’, the MHRA said, and while the study did not prove a link the findings raised an important safety issue that warranted action.
A statement from the agency also pointed out that the risk is much lower than the risk of neurodevelopmental disorders in children born to mothers who take valproate during pregnancy.
But they now recommend that male patients and their partner use effective contraception during valproate treatment and for at least three months after stopping use of the medication.
In addition, patients should not donate sperm during treatment with valproate and for three months after stopping, the MHRA said.
For those patients wishing to change their treatment in response to the new recommendation, priority should be given to male patients who are planning to father a child in the next year, the MHRA added.
No one should stop taking valproate without advice from a specialist because of the importance of keeping their condition under control, they said.
Dr Alison Cave, chief safety officer at the MHRA, said: ‘Valproate is an effective medicine in the treatment of epilepsy and bipolar disorder.
‘Men taking valproate should be aware that there is now evidence of a potential small increased risk of their child having a neurodevelopmental disorder if their partner becomes pregnant while they are on valproate.
‘While the risk to a child is lower than the risk associated with a mother taking valproate in pregnancy, we recommend that men taking valproate and their partners follow the updated guidance and use effective contraception.’
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