Statement on Substitution of Generic Antiepileptic Drugs
Position on Switching of Antiepileptic Drugs
The Epilepsy Foundation is seriously concerned about the substitution of antiepileptic drugs (AED) by pharmacists and public and private payers, without the knowledge and prior approval of the patient and treating physician.
Generic products present a welcome opportunity to save costs for people who require chronic use of medication; private insurers, health care plans, and state and federal payers of health care treatment may also require the use of lower cost generic versions of products whenever available. This is generally beneficial to all people with chronic health conditions, including people with epilepsy. However, since the inception and increasing reliance upon the use of generics, experts in the treatment of epilepsy have consistently reported a significant number of people who cannot be switched from brand name to generic, generic to brand, or among generic to generic versions of the same therapeutic agent, without experiencing side effects, toxicity, or unexpected “breakthrough” seizures.
Recent literature reviews document consistent international opinion that despite existing regulatory criteria to ensure the bioequivalence of generic versions of anti-epileptic therapeutic agents, a small but significant number of people with epilepsy continue to experience adverse reactions when switching. Recent studies confirm that for those people who experienced adverse reactions, the level of medication in their blood was dramatically different, even while on reputedly equivalent products. Other studies document a significantly higher rate of emergency room visits by people following a switch in medications, and the “switch-back” rates of anti-epileptic products (that is, individuals being returned to their previous product under a physician’s guidance) is a great deal higher than in other drug products.
Maintaining continuity of supply of a therapeutic agent, by the same manufacturer using the same manufacturing process, appears to be a significant factor in optimal seizure control with minimal side effects for these individuals. Although drug costs are the rationale for drug substitutions, for individual patients and their insurers such switching may in fact increase costs, if breakthrough seizures or increased side effects occur. The costs of treating medical complications, including emergency room visits, doctor’s office visits, drug level monitoring to re-establish medications to a therapeutically effective level - not to mention the potential for accidents, severe bodily harm or even death that can result from severe seizures - can greatly outweigh the intended savings from the mandatory substitution of products.
The reasons for such treatment failure in drugs that meet the Food and Drug Administration’s (FDA) requirements for bioequivalence remain unknown and largely unstudied. There are no accepted protocols to identify those people who may have difficulty with switching, although if one has had difficulty in the past, it is anticipated that this may occur in the future. There is therefore an urgent need for research to help understand and guide regulators and medical providers on the nature and extent of the problems related to switching. In addition, the Epilepsy Foundation and its experts strongly recommend that the FDA’s process for approval, surveillance and oversight of antiepileptic therapies be reviewed and improved in order to promote medically appropriate substitution of generic products.
Until both the research and the review of standards and guidelines for determining bioequivalence in antiepileptic therapies occurs, the Epilepsy Foundation recommends extreme caution be taken when switching patients among different versions of a therapeutic agent. Current experience suggests that most patients will be able to switch safely and effectively from one version of a product to another; however, because of the significant number of people who will have difficulty with switching, including potentially serious and costly consequences, and because those people cannot be identified in advance, the Foundation advises that when a switch is contemplated, both the treating physician and the individual be informed and agree in advance, and have the option to stay on the product of choice, or to have the switch occur only under the guidance and direction of the treating physician. The results of such switching should be monitored closely for a few weeks after a switch occurs, and any problems or concerns that arise should be reported to the treating physician, to the pharmacist, and to the FDA’s Medwatch program. For information, call 1-800-FDA-1088 or visit the web site at http://www.fda.gov/medwatch.
Medically appropriate and necessary treatment for people with epilepsy requires access to the full range of medication options available today, including those that work best for the individual to control his or her seizures with minimum side effects, as prescribed by the treating physician. Availability includes reimbursement for such necessary treatments at reasonable levels by federal, state, and private payers, and the assurance that physicians and patients determine together the optimal products for their seizure control. Accordingly, regulatory agencies, providers and payers should have policies in place that allow physician and patient direction to override mandatory substitution policies, and to require informed consumer and physician consent prior to any substitution. If substitution cannot occur for medical reasons, the individual with epilepsy should continue to have access to the drug of choice, at reasonable affordable prices, to ensure optimal safety for the patient and the public.
People with epilepsy are also encouraged to ask the pharmacist to note in the records that they and their physician be notified prior to any substitution of their anti-epileptic medication. If appropriate, patients and physicians can also identify the product, including the manufacturer’s name, that has been successful for maintaining seizure control with minimal side effects. Most pharmacists are happy to make this information a part of the patient’s record.
For additional information and resources, visit the Epilepsy Foundation at www.epilepsyfoundation.org/.
Statement Approved by the Epilepsy Foundation Board of Directors May 2009