Epilepsy Drug – Safety Review on Risks & Warnings
September 2017 saw the start of a long awaited review of the safety of sodium valproate when taken during pregnancy.
Sodium valproate has a good history of reliably controlling epileptic seizures but it is known to have the potential to cause damage to the unborn child when taken in pregnancy. It has been claimed that physical defects such as spina bifida and developmental conditions such as autism are caused by taking sodium valproate in pregnancy.
Families claiming to have been affected are unhappy that the drug company, Sanofi, failed to give what they regard as sufficient warnings about the adverse effects in pregnancy at a time when the risks were known.
The European-wide safety review taking place this year will take information from all interested parties including patients, doctors and pharmacists. A public discussion forms part of the review programme. This took place in London between 25 and 29 September and patients in particular were invited to contribute to the discussion with their experiences.
The review is seeking to investigate three issues:-
- The views of interested parties on the risks of taking sodium valproate during pregnancy, including its potential effect on the child,
- The views of interested parties on the measures currently in place to reduce the risks of using sodium valproate during pregnancy, and
- What other measures should be taken to reduce the risks of using sodium valproate during pregnancy.
The issues under the spotlight in this Review concentrate on the current use of the drug and the information given to patients and clinicians now and in the future. The questions are not directly investigating advice given to patients in the past.
Parents and their affected children are watching the proceedings closely and remain hopeful that the enquiry will lead to the opportunity of legal claims to bring the drug company, Sanofi, to account for alleged past failures.
Previous Court Action
The lead up to this enquiry has been a long and winding road. The claim has met with different levels of support throughout Europe. In France, the government supports the legal action of its citizens and has put aside nine million pounds to compensate the families.
In England and Wales, the situation has not been as straight forward. A group claim was commenced in around 2004 but was abandoned in 2010 when Legal Aid was withdrawn shortly before the trial. Families were distraught at the loss of the opportunity to have their cases heard but, with the threat of an award of costs against them, they signed letters agreeing to drop their claims permanently.
The acknowledgement of the potential liability in France has raised the profile of the issues in the rest of Europe, and the European Medicines Agency, through its Pharmacovigilence Risk Assessment Committee (PRAC), will now examine whether warnings about the risks to unborn babies are appropriate.
Sodium valproate was introduced in the 1970s. It takes different names including Epilim, Depakine, Depakote and Stavzor. Its usefulness in the control of epilepsy is not in question and it is a very important medication for those with the illness.
The drug has been known for some time to cause birth injuries but warnings to patients were initially slow in being publicised. Concerns first appeared in scientific studies in the 1980s and 1990s, but it was some time before warnings appeared on medication packaging and information leaflets.
Communication of such risks to patients to a substantial degree was slow to emerge until patient information leaflets were distributed in 2005. The medicines regulator has said warnings were updated as more information became available. However, only as recently as 2016 was the warning was added to the outside of sodium valproate medication packaging, demonstrating that communication of the risk was still developing.
The Court claims brought by parents in England and Wales in 2004 were mainly based on an alleged failure of the drug company to provide sufficient warning throughout the 1990s.
The known risks are substantial. Babies exposed to sodium valproate medicines in the womb are said to have a 10-11% chance of developing physical abnormalities. There is also said to be a 4 in10 chance of developing cognitive problems, such as learning disabilities and autism. Each pregnancy therefore stands a high chance of suffering injury.
Families affected by the issue will be hoping that the enquiry will produce evidence demonstrating that Sanofi knew of the terrible risks much earlier than the point when it started to publicise the warnings to patients.
If such evidence is identified, it may be able to support new legal action although any such claims would be subject to the usual elements required for a successful legal claim. Claimants would have to prove that:-
- Sanofi was aware of risks to patients and failed to relay those risks to the medical profession, and
- Medication was taken during the period when proper warnings were not issued, and
- The patient would have acted on warnings and would have stopped the medication (or not started taking the medication), and
- The child’s injuries are of the sodium valproate-type injuries and not due to other factors (eg genetic) or medical conditions.
Each of the above elements carries particular issues and challenges.
Each mother would need to be able to show that she would have acted on proper warnings of the dangers of sodium valproate and that she would have either stopped the drug before attempting pregnancy or stopped the drug when pregnancy was discovered.
As epilepsy can be a debilitating and destructive disease, varying in severity from patient to patient, proving that the drug would have been stopped or not used, may be more difficult to prove for some patients. Certainly, the advice from clinicians is that patients with epilepsy must not stop the medication without taking medical advice.
Epilepsy is a serious condition which needs control. Although a seizure generally does not affect the unborn child, its effects on the mother can be significant. Physical injuries to mother and unborn baby are highly possible due to the sudden collapse of the pregnant mother and constant contraction of muscles causing aggressive movements and trauma. Contraction of muscles can also impair breathing. Moreover, long uncontrolled seizures are known to result in the mother suffering brain damage. Not taking or stopping sodium valproate is therefore not always an easy choice for some patients.
As sodium valproate must be gradually decreased over a number of weeks to safely withdraw from the drug without causing injury to the mother, the mother must also be able to show that her child’s injury was not caused by being on the drug at the start of pregnancy when the effect of sodium valproate was unavoidable.
Paediatricians and neurologists are likely to be able to state on the balance of probabilities whether a particular condition or injury suffered by the child is due to sodium valproate damage. They may also be able to advise whether the particular damage was avoidable when allowing for the safe withdrawal period of the drug.
The outcome of the enquiry is much anticipated. The PRAC will now consider the evidence put forward during the public part of the enquiry in September and it will formulate a report on its findings. This report may well contain recommendations. These recommendations may provide evidence that there were failures in the past.
If legal claims were successfully re-started, the potential compensation could run into similar figures of that put aside by the French Government. However, for those claimants who were forced to abandon proceedings in 2010 and sign agreements forgoing their right to pursue claims in the future, the path may not be easy. Court intervention may first be required to set aside the past agreements as an abuse of process or otherwise allow such fresh claims.
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