Latest news with #valproate
Medscape
11-07-2025
- Health
- Medscape
EMA Questions Valproate Prescribing Restrictions for Men
The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has announced it is assessing new data on the potential risk of neurodevelopmental disorders (NDDs) in children born to men treated with valproate during spermatogenesis. The announcement comes after controversial new precautionary measures for the treatment of male patients with valproate medicines were imposed in January 2024. The cautionary approach to valproate — a medicine used to treat epilepsy, bipolar disorders, and in some countries migraine — came about as a result of a post-authorization safety study (PASS) funded by a consortium of marketing authorization holders for valproate and related substances. After examining the results, PRAC recommended that valproate treatment in male patients be started and supervised by a specialist in the management of epilepsy, bipolar disorder, or migraine. It also said that valproate treatment of male patients should be reviewed regularly to consider whether it remains the most suitable treatment, particularly if the patient is planning to conceive a child. Original Study Suggests Risk PASS was a population-based retrospective study that used data from multiple Scandinavian registry databases in Denmark, Norway, and Sweden, together with other available information, to evaluate the association between paternal exposure to valproate and the risk of NDDs in offspring, including autism spectrum disorders, intellectual disability, communication disorders, attention deficit/hyperactivity, and movement disorders, as well as congenital abnormalities. The results suggested a potential increased risk to children born to men treated with valproate during the 3 months before conception. This led PRAC , and later the UK's Medicines and Healthcare products Regulatory Agency, to recommend precautionary measures for the treatment of male patients with valproate medicines. These measures were in addition to restrictions already in place since 2018 to avoid valproate exposure in pregnancy due to evidence of an increased risk of malformations and developmental problems. Second Study Casts Doubt At that time, the committee acknowledged that the PASS data had limitations but concluded that the potential risk warranted informing patients and healthcare professionals. However, a study published in JAMA in June 2024 using a subset of the same data cast doubt on the PASS findings. That study aimed to replicate the PASS results using the nationwide Danish data sources that had been used in PASS. In this later study, 1336 children among the total cohort of 1,235,353 children had been born to fathers who filled prescriptions for valproate during spermatogenesis. No association was found between paternal valproate use and risk of major congenital malformations or NDDs, the researchers said. The researchers highlighted that the PASS results stemmed from an observational study report prepared by contract research organization IQVIA. "We were unable to replicate the IQVIA study results," they said. Latest Study Shows No Risk The same research team subsequently published a research letter in JAMA in May 2025, in which they said that they had access to only limited information about the IQVIA study at the time of their 2024 report. Following publication of the detailed IQVIA report, the team conducted analyses to explore the impact of methodological choices and definitions used in that study. "Paternal valproate exposure was not associated with an increased risk of NDDs," they concluded. This was the case for the composite endpoint of all NDDs and "remained robust" across analyses of specific NDDs, expanded definitions of NDDs, valproate dose, time trends, polytherapy, and analyses restricted to fathers with epilepsy. PRAC said that, in the light of this latest study's inability to replicate the signal for NDDs in children with paternal valproate exposure and a more recent systematic review from Australia that also showed "no clear evidence for an adverse impact of paternal antiseizure medication use on offspring outcomes," the committee has initiated a signal procedure to understand the difference in the findings across the studies. It has also requested further information and analysis from valproate marketing authorization holders. The EMA will communicate further when more information becomes available, it said.
Medscape
09-06-2025
- Health
- Medscape
UK Valproate Restrictions in Men Justified? New Data
A large Danish cohort study showed no significant increase in neurodevelopmental disorders (NDDs) among children fathered by men taking valproate during spermatogenesis, challenging earlier safety concerns and current UK restrictions on valproate use in men. As previously reported by Medscape Medical News , the decision to restrict the drug in women and in men younger than 55 years was made in January 2024, after the UK Medicines and Healthcare products Regulatory Agency issued new guidance on the drug's use. 'Paternal exposure to antiseizure medication in association with conception is unlikely to pose any major risk for the offspring,' the investigators led by Jakob Christensen, DrMedSci, consultant neurologist at Aarhus University Hospital and professor at Aarhus University, Aarhus, Denmark, noted. The study was published online on May 22 in JAMA Network Open . Unnecessary Precaution? In the US and Europe, there is strong guidance about avoiding valproate in pregnant women and women of childbearing age due to an elevated risk for birth defects and other developmental problems. In January 2024, the European Medicines Agency's (EMA's) safety committee (Pharmacovigilance Risk Assessment Committee [PRAC]) expanded precautionary measures on valproate use to men considering fatherhood. The advisory was fueled largely by an observational study by the contract research organization IQVIA. The study showed that about 5 out of 100 children had an NDD when born to fathers taking valproate during the 3 months before conception compared with about 3 out of 100 when born to fathers treated with lamotrigine or levetiracetam. Last summer, Christensen and colleagues were unable to replicate the IQVIA results in a study using a subset of the same IQVIA data. However, at the time, only limited information about the IQVIA study was publicly available. Once additional information from the IQVIA study became available, the researchers tried again to replicate the findings, aligning their methods more closely with the IQVIA study. Despite using the same methodology and incorporating additional data, they were still unable to replicate the IQVIA findings. Their conclusion remained unchanged — there was no statistically significant increased risk for NDDs. Specifically, among 961 children exposed to paternal valproate monotherapy and 1401 exposed to lamotrigine or levetiracetam, there was no significant increase in risk for NDDs (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.67-1.54). 'This finding remained robust across analyses of specific NDDs, analyses of valproate dose, analyses accounting for time trends, analyses allowing for polytherapy, analyses expanding the definition of NDDs, analyses restricted to fathers with epilepsy, and analyses with a restricted exposure window,' Christensen and colleagues reported. Restricting analyses to fathers with epilepsy of unknown cause yielded a higher risk (aHR, 2.48; 95% CI, 1.13-5.44), but this association was no longer significant in analyses matched on birth year (aHR, 2.33; 95% CI, 1.00-5.44). Additional sensitivity analyses (restricting exposure window, excluding children with epilepsy or maternal epilepsy, and accounting for polytherapy) consistently showed no elevated risk for NDDs associated with paternal valproate exposure. 'We've examined this issue from many angles and still find no evidence supporting the concern behind EMA's recommendations,' Christensen said in a news release. Will the EMA Reconsider? Reached for comment, Aatif Husain, MD, epileptologist, neurologist, and sleep medicine specialist at DukeHealth, Durham, North Carolina, said, 'There seems to be a fair amount of literature' suggesting no increased risk for NDDs in children whose fathers use valproate. 'A recent systematic review that included 10 other studies came to this same conclusion,' said Husain, who wasn't involved in the Danish study. Taken together, the data 'would probably move EMA to relook at their guidance to see if it needs to be modified,' he said. Medscape Medical News reached out to the EMA press office for comment and received the following response. 'As with every medicine authorized in the EU, EMA continues monitoring and supervising the safety of these medicines. This includes monitoring information from various sources, such as spontaneous reports, clinical studies, scientific literature, and management of safety signals, which consists of a set of activities to determine whether there are new risks associated with an active substance or a medicine or whether known risks have changed. Should there be any updates, EMA will communicate them via the PRAC Highlights.' Husain told Medscape Medical News that neither the FDA nor the American Epilepsy Society has issued guidance on valproate use in men 'because the data has not been strong enough.'
Daily Mail
29-05-2025
- Health
- Daily Mail
EXCLUSIVE My four children have all been left disabled after doctors told me I HAD to take this drug during pregnancy to avoid killing them
A mother-of-four whose children have all been left with disabilities after doctors encouraged her to take a drug during pregnancy without warning her of the risks has heartbreakingly revealed how her daughter is a 'prisoner in her own bedroom'. Karen Buck, 53, was diagnosed with epilepsy when she was 12 years old and initially had two drugs pumped into her that completely 'zombified' her and left her feeling like she was walking around 'asleep'. The devastating trauma she has faced throughout her life began shortly after - when a group of men took advantage of her vulnerability and gang raped her at the age of 13. Numb and sedated by the drugs, she was moved onto Epilim - one of the leading sodium valproate drugs to control epilepsy seizures. But this would tragically mark the start of another four decades of torture. Despite it being known since the 1970s that valproate can harm babies in the womb, Ms Buck and countless other expectant mothers have been prescribed the drug over the last five decades without being warned of the risk of birth defects. An estimated 20,000 children were exposed to the epilepsy drug while in the womb and many are now adults living with neurodevelopmental disorders such as autism and ADHD. While Epilim initially worked well for Ms Buck, her children, who are now in their 20s and 30s, were all later diagnosed with foetal valproate syndrome after doctors told her to carry on taking it - even upping her dosage - during pregnancy. Her third child, Bridget, was born with severe brain damage and spina bifida, is paralysed from the waist down and has so many complex disorders that she has been referred to as the 'world's worst affected child'. In an emotional interview with MailOnline, Ms Buck, from Stanmore, north-west London, said: 'Bridget is paralysed, she's brain damaged. She's bed bound and she's a prisoner in her own room.' Bridget, who is now 27, must be surrounded by oxygen tanks as she has Lennox-Gastaut syndrome, meaning she constantly has seizures which can cause her to stop breathing. Ms Buck has always cared for her daughter 24/7, even from a young age when she decided to take her out of school because she was being abused so badly. The mother-of-four has revealed how not only did doctors not warn her of the risks of taking Epilim while pregnant, they made sure she stayed on it and increased her dosage so she 'wouldn't kill her baby by having a seizure'. Ms Buck is one of thousands of parents across the world who are fighting for compensation. Her other three children, Josephine, 36, John, 34, and Christine, 22, have all faced individual battles as a result of being harmed by valproate, Ms Buck says. Josephine has spinal issues, crystallisations of the joint, nerve damage, polycystic ovaries and small hands. John has a twisted oesophagus, dyslexia, a hiatal hernia, and sleep hyponoia. And Christine has a heart condition and problems with her ears and back. But it was Ms Buck's pregnancy with Bridget that was the most complicated. At one stage, the foetus was in her ovary and her tubes - before eventually moving around to her womb. During the pregnancy, she started being 'violently sick' to the point it was inducing seizures. Pictured is Bridget Buck as a young baby. She was born with several defects and is now bed bound at age 27 Ms Buck explained: 'They increased my dosage while I was pregnant and I questioned it. I said, "I'm being violently sick. Is it wise to put my medication up? Couldn't you give me something for the sickness, rather than the seizures?" 'And I'll never forget this, they then said to me that if you have a seizure, you will kill your baby, so it's important for us to give you the medication.' Ms Buck says Bridget and her other children have been 'deprived' of a normal life as a result of her not being warned of the risk of birth defects. Speaking about Bridget's day-to-day life, she said: 'Every day is in the bed. Every day is in the same routine. It's get up, wash her, change her, medicate her, entertain her, feed her. If she has a seizure, you have to be on the ball. 'You've got to give her oxygen, emergency medication.' Ms Buck says the list of disorders that her daughter has is so long that she is known as 'the world's worst affected child'. 'She's paralysed from the waist downwards. She can't eat normal foods. She can't pick up a knife and fork and eat food. 'She couldn't pick up an orange and start eating it because the skin would choke her. 'If she's feeding and she starts coughing it's gone into the wrong part of her body, it's gone into her lungs.' Ms Buck was yet again rocked by another battle when she was diagnosed with cancer. She has since brought in a carer to assist her in looking after Bridget. In February 2024, families whose lives have been ruined by the scandal were given a fresh glimmer of hope when England's patient safety commissioner called on the Government to compensate those affected. Dr Henrietta Hughes recommended a £100,000 payout after describing the drug's damage as a 'bigger scandal than thalidomide', referring to the morning sickness drug which led to thousands of mothers giving birth to disabled babies. Ministers said they would consider and respond to compensation recommendations but a deafening silence has left mothers fearing they have once again been forgotten - as they fight for compensation while they are still alive. The Hughes report came after Baroness Cumberlege published a lengthy review into sodium valproate and two other medical interventions in 2020, which highlighted the denial and dismissal of patient concerns. The Government issued an official apology in 2021, but the mothers fighting for justice want 'action not words'. And while countries such as France have started paying out victims, the UK Government is still not acting. Speaking about the lack of urgency to redress affected families, Ms Buck said: 'I feel disgusted by the authorities. I feel disgusted by the Government. I feel disgusted by the regulators. I feel disgusted by the NHS neurologists. And I feel disgusted by the drug company because they should have put it in place. 'I feel they are not taking accountability to put things right. If they explained to me this drug could cause damage to my children I would have had my tubes tied right from the start, not afterwards so that I wouldn't have any more. I wouldn't be able to cope looking after more children. 'Bridget is the world's worse and it's taken a lot of me.' Speaking of the scale of the scandal, she added: 'It's bigger than thalidomide. It's bigger than the contaminated blood scandal. It's bigger than the Post Office scandal, and it's getting bigger.' Ms Buck continued: 'I've been through the courts, it failed. I've witnessed the Cumberlege report, that went on for five years and then now the Hughes report, nothing's come. 'Do I trust them? No. They've not listened to all the family stories. I listen day in, day out, to the families. Nobody's listening to them. Until they show me something for all my families that I'm listening to, then I will say, OK.' 'You need to practice what you preach. Don't throw out easy apologies. 'You have done damage to all these people. You are accountable for this and you've let all these women down, that's what makes me angry.' Ms Buck says she has been let down throughout her life, including when she was prescribed drugs that 'zombified' her as a 12-year-old. She was initially diagnosed with epilepsy due to the trauma she had suffered when she was a young girl, when her parents split up and her mother's new boyfriend started abusing her. The initial epilepsy drugs left her feeling like a 'zombie' and she wanted to stay away from her mother's home because she was living with someone abusing her. She was only on those drugs for three to six months, but during that time she was gang raped by men who preyed on her vulnerability and sleepiness. Recalling the traumatising ordeal, she said: 'I was only young, I was probably 12 or 13, very young. I actually kept that all to myself, I was so scared. The only person I told was a doctor but he just overlooked it like I was a child seeking out attention. He said, "It was just a drug making you hallucinate, we'll put you on a different drug". I'm not imaging this, these things happened to me. Ms Buck was then put on Epilim but throughout all four pregnancies was never told there were any risks. 'I should have had more guidance, I should have had the support,' she said. 'They should have given me a choice, they didn't tell me anything about what this drug was capable of doing. 'It is appalling the way we have been treated.' Campaigners have proven that concerns over sodium valproate, commonly known by brand names Epilim, Episenta and Depakote, were first identified in the 1970s but the drug only started to be restricted by the government in 2018. They ruled that valproate must not be prescribed to women or girls of childbearing potential unless they are on the pregnancy prevention programme. It came after the Medicines and Healthcare Products Regulatory Agency said up to four in 10 babies were at risk of development disorders if the drug was taken during pregnancy and and one in 10 at risk of birth defects. A drug safety update in January 2024 stated that women and men under 55 should not be prescribed the drug unless two separate specialist agree there is no other effective treatment. Jo Cozens, the Chairperson of Organisation for Anti-Convulsant Syndrome (OACS Charity) who support families harmed by valproate, told MailOnline: 'I'm extremely disappointed frustrated beyond words.' Ms Cozens, who has requested urgent meetings with the Government but has not heard back, said: 'Not even an acknowledgement is so insulting to families.'
