Anti-epileptic drugs – the problem with switching
For many people with epilepsy, anti-epileptic drugs (AEDs) are a lifeline. They control, or minimise, the number of seizures a person with epilepsy experiences. But what happens if these drugs are inadvertently changed?
For many people with epilepsy, anti-epileptic drugs (AEDs) are a lifeline. They control, or minimise, the number of seizures a person with epilepsy experiences. They allow them to live a full and active life, free from the uncertainty of when a seizure may occur. Up to 70 per cent of people with epilepsy can become completely seizure free by taking epilepsy medicines.
The problem with switching
It's vital that AEDs are taken exactly as prescribed to be effective. Even very tiny changes to medication, dosage or preparation can have an adverse effect on a person's seizure control. This extends to any changes between branded and generic versions of the same medication, for example sodium valproate and Epilim.
Generic prescribing is the process of treating a patient with a non-branded version of an AED. Generic versions tend to cost less than branded medicines, thus generic prescribing could save the NHS money. The problem is that the generic version of an AED is not 'exactly' the same as the branded version, or in fact another generic version of the AED.1
It is true that each of the different versions of an AED contain the same type and volume of active medical ingredients. However, the inactive ingredients can differ between the different versions of the AED, as can the rate and extent of absorption of the medical ingredient 2-4. So each version of the drug might not be absorbed in exactly the same way and a dose change of the active ingredient can occur.
We don't believe that only branded versions of an AED should be prescribed. But it's vital that health professionals and pharmacists ensure a consistent supply of a person's AEDs, whether a branded or generic version. Even tiny changes in dose are expected to have a clinical impact (which is why patients are counselled about the importance of taking their AEDs as prescribed and on time). Thus unintentional changes in dose (by switching) could have an unintentional clinical impact and possibly lead to a breakthrough seizure or adverse side-effects.
Loss of seizure control is a major issue for many people with epilepsy, affecting employment, education and social life. For example, a single seizure can cause the loss of a driving license for a year, and this may impact on a person's quality of life or ability to get to work.
Risk of death
A lack of seizure control is also a known risk factor for accidents and sudden unexpected death in epilepsy (SUDEP). SUDEP is where a person with epilepsy dies suddenly and unexpectedly, and no obvious cause of death can be found. A recent study found that 'patients who remain seizure free over 12 months are at a lower risk [of SUDEP]' 5. Yet just last month, the Medicines and Healthcare products Regulatory Agency (MHRA) issued new guidance concerning switching between different manufacturers' brands of AEDs. It appears that patients and patient groups were not consulted prior to the introduction of the guidance.
New MHRA guidance
The new MHRA guidance places AEDs into three categories:
• Category one: For these drugs doctors are advised to ensure that their patient is maintained on a specific manufacturer's product.
• Category two: For these drugs the need for continued supply of a particular manufacturer's product should be based on clinical judgement and consultation with patient and / or carer taking into account factors such as seizure frequency and treatment history
• Category three: For these drugs it is usually unnecessary to ensure that patients are maintained on a specific manufacturer's product unless there are specific concerns such as patient anxiety, and risk of confusion or dosing errors.
Epilepsy Action supports the development of category one as there is substantial evidence to suggest that drugs listed in this category should not be switched. Category two is in accordance with NICE clinical guidance and is current practice.
"...it's vital that health professionals and pharmacists ensure a consistent supply of a person's AEDs, whether a branded or generic version."
However, we have major concerns about category three. This category provides a green light for some drugs to be switched without input from, or discussion with, patients. Such action directly contravenes advice contained in NICE clinical guidance on managing the epilepsies and the NHS health mandate: 'No decision about me, without me'.
No evidence
Having sought the opinions of our clinical advisors, some of the UK's leading epileptologists, we are concerned that there is no clinical evidence to support the view that switching between preparations of the specific drugs listed is safe. In fact evidence has shown that switching between the branded and generic versions of levetiracetam – one of the category three drugs - can have an adverse effect on a patient's health6. Under the new guidelines, levetiracetam could be switched automatically without any discussion with the patient.
A 2011 paper in the scientific journal Epilepsia7 also indicates the potential problems that switching medication can cause for people with epilepsy. In a review of patients who had been switched from a branded to a generic version of levetiracetam in the USA, 43 per cent were switched back to their original brand due to problems.
Further to this, some drugs listed in category three currently have no generic version. As such, there is no evidence that switching between preparations of these drugs is safe. It is a concern that these drugs will remain in category three by default when a new generic is released
"...there is no evidence that switching between preparations of these drugs is safe."
Action for patient safety
In light of our concerns we strongly believe that category three should be suspended immediately to maintain patient safety. The listed drugs can be moved into category two. We believe that this suspension should be in place until wider consultation on the implications of using a three category system has been completed.
We have asked the MHRA to make available the full report or review of the evidence, and a list of the evidence used, as a priority so that this can be evaluated by epilepsy experts.
We have also sought an assurance that should category three remain, that drugs are only placed on this list when a generic version of these drugs has been released and the drugs have been fully evaluated to see if they are safe.
A single seizure or breakthrough seizure can be catastrophic for a person with epilepsy. We hope that patient safety continues to be a priority. This is the only way to be sure that patients are not being put at risk.
References
1. Crawford P, Hall W, Chappell B et al (1996). 'Generic Prescribing for Epilepsy. Is it Safe?' Seizure; 5:1-5
2. Besag F M C. (2000) 'Is Generic Prescribing Acceptable in Epilepsy?' Drug Safety no.3, pp173-182.
3. Richens A (1997). 'Impact of Generic Substitution of Anticonvulsants on the Treatment of Epilepsy'. CNS Drugs; 8 (2): 124-133.
4. Guberman A, Corman C. Generic substitution for brand name antiepileptic drugs: a survey. Can J Neurol Sci 2000; 27:37–43.
5. Epilepsy mortality and risk factors for death in epilepsy: a population-based study, Ridsdale et al, British Journal of General Practice, 2011 May; 61(586): e271–e278
6. Clinical experience with generic levetiracetam in people with epilepsy, Chaluvadi et al, Epilepsia, 52 (4) 2011
7. Clinical experience with generic levetiracetam in people with epilepsy, Chaluvadi et al, Epilepsia, 52 (4) 2011
About the author:
Vikki Brown is Senior Policy and Campaigns Officer (Health) at Epilepsy Action. Vikki graduated from the University of Wales Swansea with a BSc. Econ degree in social policy focusing on health, education and models of social policy. This led her to a varied career working in the third and public sectors for a variety of organisations including the Royal College of Nursing, Alzheimer's Society and the Department of Health.
In a voluntary capacity Vikki established and led a national charity for three years. She has vast experience in policy, research and project management. At Epilepsy Action, her responsibilities include developing and communicating Epilepsy Action's position and response in relation to public policy issues relevant to people with epilepsy, developing and delivering policy campaigns and carrying out research.
Contact Vikki on 0113 210 8800 or at campaigns@epilepsy.org.uk
Closing thought: What are your thoughts on the latest MHRA guidance on AEDs?
