Generic Antiepileptic Drugs Research Articles

The Controversy over Generic Antiepileptic Drugs

As patent protection ends for the next generation of antiepileptic drugs (AEDs), a complex debate continues over generic substitution of AEDs. On one hand, generic drug formulations provide cost savings for patients and society. On the other hand, patients with epilepsy and physicians are wary about the adequacy and efficacy of the Food and Drug Administration's (FDA) standards for generics. This article reviews current and proposed bioequivalence test procedures, summarizes new generic AED formulations and their costs, and discusses potential pitfalls in the current standards. These shortcomings include certain pharmacokinetic factors and clinical pharmacologic factors that may affect bioequivalence of generic AEDs, and statistical limitations of the standards. While the drug concentration differences between the brand name drug and each generic formulation are unlikely to be substantial, the differences with generic-to-generic switches will be greater and potentially clinically significant. Conversely, owing to their more favorable pharmacokinetic profile, newer AEDs may be less prone to problems with generic substitution than older ones. Unfortunately, very few data are available to guide decisions regarding what is best for an individual patient. Based on new prediction methods, generic substitution should be safe for many patients but identifying them ultimately requires more rigorous study.

Seizure Outcomes Following the Use of Generic versus Brand-Name Antiepileptic Drugs

The automatic substitution of bioequivalent generics for brand-name antiepileptic drugs (AEDs) has been linked by anecdotal reports to loss of seizure control. To evaluate studies comparing brand-name and generic AEDs, and determine whether evidence exists of superiority of the brand-name version in maintaining seizure control. English-language human studies identified in searches of MEDLINE, EMBASE and International Pharmaceutical Abstracts (1984 to 2009). Randomized controlled trials (RCTs) and observational studies comparing seizure events or seizure-related outcomes between one brand-name AED and at least one alternative version produced by a distinct manufacturer. We identified 16 articles (9 RCTs, 1 prospective nonrandomized trial, 6 observational studies). We assessed characteristics of the studies and, for RCTs, extracted counts for patients whose seizures were characterized as 'controlled' and 'uncontrolled'. Seven RCTs were included in the meta-analysis. The aggregate odds ratio (n = 204) was 1.1 (95% CI 0.9, 1.2), indicating no difference in the odds of uncontrolled seizure for patients on generic medications compared with patients on brand-name medications. In contrast, the observational studies identified trends in drug or health services utilization that the authors attributed to changes in seizure control. Although most RCTs were short-term evaluations, the available evidence does not suggest an association between loss of seizure control and generic substitution of at least three types of AEDs. The observational study data may be explained by factors such as undue concern from patients or physicians about the effectiveness of generic AEDs after a recent switch. In the absence of better data, physicians may want to consider more intensive monitoring of high-risk patients taking AEDs when any switch occurs.

The Value of Specifying Brand-name Antiepileptic Drugs

T HE PATENT LIVES OF most of the newergeneration antiepileptic drugs (AEDs) have either expired or come close to expiration. This is despite occasional attempts by the pharmaceutical industry to extend patent lives by creating a variation of an existing compound/AED, often in the form of an extendedrelease version, eg, Lamictal XR and Keppra XR. Inevitably the question of generic substitution of our patients’ AEDs arises, usually prompted by the paying insurance companies whose main interest is the bottom line, though it is not infrequently prompted by the (self-paying) patients or their families. This brief commentary will not attempt to be a comprehensive review of this topic, which have already been written. There is a saying in the management of epilepsy that most of us who treat such patients are well aware of: “If it ain’t broke, don’t fix it.” That simply means of course that if our patients were seizure free and without any (significant) adverse effects, we would not change their medication regimen (with the exception of trying to reduce or even discontinue treatment with AEDs in a successfully treated patient). In this scenario, there should be no reason to change from one AED to another. I am not going to argue whether or not the generic form of an AED is the same as the brand form, though I think even the most ardent supporters of generic substitution will grant that there are differences between brand-name AEDs and generic drugs and among the multiple generic forms themselves. If cost were not an issue, there would be no contention at all (at least in this scenario of a successfully treated patient). Substitution of brand-name AEDs with generic AEDs can and does lead to breakthrough seizures. Unlike other diseases, a single breakthrough seizure due to change in delivered medication (dose) may lead to dire consequences, including loss of one’s driver’s license, injury (to self and others), loss of employment, hospitalization, or even death. Patients with epilepsy are not simply dealing with minor adverse effect profile changes when their AED is substituted for a generic form, though they are not exempt from other comorbidities associated with such change. In a study of the generic substitution of lamotrigine in patients with epilepsy, the most prevalent comorbidity was high blood pressure, followed by depression, asthma, diabetes, and angina. It has been shown that the switch-back rates of patients who were substituted generic for brandname drugs were substantially higher for AEDs than non-AEDs. This was likely the result of increased toxicity and/or loss of seizure control associated with the use of generic AEDs. There was a dramatic, recent case report of a 29-year-old man who had been taking high-dose (800-mg/d) Lamictal, which was abruptly substituted with 800-mg/d generic lamotrigine. He developed anticonvulsant hypersensitivity syndrome. As a consequence, the Danish licensing authority now reimburses the cost difference between generic and proprietary forms of lamotrigine for all patients with epilepsy taking high doses of lamotrigine ( 30 μmol/L) to eliminate the risks associated with the arbitrary switching among types of this drug. The risks of generic substitution can be life-threatening, even independent of breakthrough seizures. None of these adverse reactions should be surprising. Generic forms of AEDs or any drugs are not the same as the propriety form. Two reviews conducted by the Food and Drug Administration showed that the average difference between area under the curve and maximum concentration of the reference and generic compounds was about 3% to 4% (standard deviation, about 3%). Notably, in 13 (5.8%) of 224 bioequivalence studies, there was a 10% or greater difference in the mean areas under the curve. One obvious problem is that the in vivo bioequivalence testing is typically done in 24 to 36 healthy adults, who are usually different than most of our patients with epilepsy. Another problem is the large numbers of different generic medications for 1 particular branded product. These many forms are of course not only different than the proprietary form but from each other. Two years after the Zonegran patent expired, there were 17 approved generic manufacturers of zonisamide. Pharmacies are currently not only substituting branded AEDs for generic Author Affiliation: Division of Pediatric Neurology, Barrow Neurological Institute/St Joseph’s Medical Health Center, Phoenix, Arizona.

The economic implications of generic substitution of antiepileptic drugs: a review of recent evidence

Background: The US Food and Drug Administration (FDA) considers generic and branded drugs to be therapeutically equivalent if they are pharmaceutically equivalent and bioequivalent. The American Academy of Neurology (AAN) disagrees and opposes generic substitution of branded antiepileptic drugs (AEDs) without physician and patient approval due to the risk of loss of seizure control. Objective: To review the evidence to date surrounding the economic impact of brand-to-generic substitutions of AEDs. Methods: A systematic search of PubMed and MEDLINE was conducted; the bibliographies of key articles obtained from the search were used to identify additional sources. Results/conclusion: Current literature suggests statistically higher overall healthcare costs during periods of generic AED use than during periods when branded AED are used, consistently demonstrated across different countries (Canada and the USA) and in both stable and unstable epilepsy patients, with more pronounced cost increases in patients receiving multiple generic versions. Brand-to-generic substitutions of AEDs do not necessarily reduce overall healthcare costs and may even increase them.

Bioequivalence of antiepileptic drugs: How close is close enough?

During the past few years, the use and substitution of generic antiepileptic drug products has been increasing both in the United States as well as globally. Although these less expensive products may represent an important alternative for many patients, there may be reasons for concern. Despite well-controlled regulatory studies, concerns persist regarding potential therapeutic inequivalence in some patients with epilepsy. These concerns have prompted some in the US neurology community as well as patient advocacy groups to question the current regulatory requirements for both establishing bioequivalence as well as product substitution. In addition, recent data have questioned the actual cost savings associated with generic substitution in this unique patient population. This article reviews current regulatory requirements and pharmacokinetic, biopharmaceutical, and clinical outcome issues that clinicians, pharmacists, and policymakers should consider regarding generic substitution of these complicated agents.

CLINICAL CONSEQUENCES OF GENERIC SUBSTITUTION OF LAMOTRIGINE FOR PATIENTS WITH EPILEPSY

LeLorier et al.1 studied the risks associated with patients switching to and from generic antiepileptic drugs (AEDs) in Quebec. The authors did not consider that such changes could be attributed to promotionally driven doctor and patient preferences. Industry representatives vigorously promote the idea that generics are less potent (“up to 20% less effective”) than their brand name equivalents despite Food and Drug Administration (FDA) assertions to the contrary.2 Study patients taking generics underwent dose escalations. The authors suggest that dose escalations were in response to increased side effects, but this is counterintuitive. More plausibly, anxiety-induced dose escalations contributed to side effects and, in turn, switch-backs. The unspoken hypothesis that switches to generic led to more seizures is unaddressed by the presented data, which blur psychiatric and neurologic indications for lamotrigine (LTG). LTG is used heavily in psychiatry and most recent growth in sales is driven by the psychiatric market.3 A single claim submitted with a code for epilepsy is considered sufficient evidence that LTG is being prescribed as an AED, but this is unlikely. The leading outpatient diagnostic code as well as four of five diagnostic codes for outpatient visits and two of three diagnostic codes for …

Understanding patients' perspective in the use of generic antiepileptic drugs: compelling lessons for physicians to improve physician/patient communication

BackgroundEpilepsy is a condition in which consistency of treatment is paramount to successful management and for most patients, effective seizure control can be achieved. Given the severe consequences of even a single breakthrough seizure, patients should be afforded every opportunity to succeed on their given regimens.DiscussionSome experts argue that global policy on generic antiepileptic drug substitution in epilepsy should be limited – occurring at the discretion of and with careful monitoring by the physician. While the debate continues, physicians still have daily responsibilities to their patients to help them best manage their epilepsy within the context of the current environment – the reality of which may involve switching to a generic antiepileptic drug or navigating various formulations between generics.SummaryTo provide context, this paper first reviews the main "hot button" issues fueling the ongoing generic debate, including a broad overview of the current state of the literature. The main goal however is to provide physicians with a patient perspective on generic antiepileptic drug use in epilepsy as a source of clinically useful, everyday advice to improve communication and increase patient self-advocacy, both of which are necessary for optimal patient outcome.

SAFETY AND EFFICACY CONCERNS IN SWITCHING PATIENTS WITH OVERACTIVE BLADDER (OAB) SYMPTOMS FROM BRANDED TO GENERIC ANTICHOLINERGIC MEDICATIONS

Changing from brand name to generic antiepileptic drugs (AEDs) is increasingly being advocated by the authorities, principally for budgetary reasons. However, caution should be exercised since AEDs may have a narrow therapeutic margin, the regimen with AEDs may be complex, the consequences of uncontrolled seizures may be severe, and risk of side effects is relatively high, particularly when seizures are difficult to control. This article focuses on the possible problems that can arise from the substitution of AEDs formulations, such as loss of seizure control and emergence of new side effects. We would advise that patients stay on the same formulation of the first AED, whether a brand name or generic AED. Switching AED formulations should always be done with the necessary caution and under the physician's supervision. Closer follow-up during the transitional period is necessary, and dosage adjustment may be required. The patient should be given full and correct advice about risks involved in switching AED formulations.

Há riscos na utilização de diferentes formulações de drogas antiepilépticas? Relato da ABE através de entrevista de pessoas com epilepsia

INTRODUÇÃO: Há controvérsias se drogas antiepilépticas (DAEs) genéricas são intercambiáveis com as de referência, assim como com as similares com respeito a eficácia e efeitos adversos. Este fato é de fundamental importância e ainda mais relevante em países em desenvolvimento com limitações orçamentárias na área de saúde. MÉTODOS: Após aprovação de Comitê de Ética a Associação Brasileira de Epilepsia aplicou um questionário a pessoas com epilepsia (PCE) com 18 questões de múltipla escolha: quatro relacionadas a dados sócio-demográficos e 14 sobre o conhecimento das formulações de DAEs (de referência, genéricas e similares) e da evidência de mudanças clínicas durante a troca (Teste exato de Fisher, significância 05%). RESULTADOS: 731 PCE de seis Hospitais do Sistema Público participaram, sendo que 91% eram de classes sócio-econômicas média e baixas; das PCE maiores de 18 anos, 24,4% tinha menos de 4 anos de escolaridade, 24,4% entre 5 a 8, 45,6 % tinha pelo menos 9 anos de estudo; 63% recebia mais de uma DAE (53,3% carbamazepina, 26,3% valproato de sódio); 58,1% obtinha as DAEs de órgãos públicos e 21,2% somente em farmácias privadas. Das 731 PCE consultadas, 60,6% não conhecia as diferentes formulações de DAEs (PCE com maior escolarização responderam mais corretamente, p<0.001); somente 36% sabia que a primeira DAE é a referência (maior escolarização, p<0.001); e 10% considerou genéricos "medicações oficiais do governo". Após serem instruídos sobre as formulações de DAEs, 24,7% não sabia que genéricos são mais baratos do que as medicações de referência, 32,5% considerou sua qualidade pior e somente 30% sabia os detalhes de sua embalagem (classes de maior renda, p=0.004). Durante o último ano, 25,6% receberam diferentes formulações de DAEs (especialmente carbamazepina e valproato de sódio) e 14,5% (especialmente com menor escolarização, p<0.001) referiram crises adicionais após a troca (carbamazepina, valproato de sódio e lamotrigina) e 12,2%, aumento de eventos adversos (carbamazepina, valproato de sódio e topiramato). CONCLUSÕES: O conhecimento de diferentes formulações foi pequena entre as PCE entrevistadas, e o recebimento de diferentes formulações de DAEs foi freqüente. Foi referido aparecimento de crises por 14,5% dos pacientes, principalmente naqueles de menor escolaridade, e ainda, aumento de efeitos adversos por ocasião das trocas (por 12,2%). Este fato deve alertar especialistas, sobretudo em países em desenvolvimento que DAEs devem ser consideradas um grupo especial em relação a políticas públicas de medicações genéricas e similares.

Guía de práctica clínica de consenso de la Sociedad Andaluza de Epilepsia sobre prescripción de fármacos antiepilépticos genéricos

Pharmaceutical spending in Spain accounts for 1.2-1.4% of the gross domestic product and is increasing by 5-12% per year. One of the measures adopted by the government to cut this spending is the possible substitution of original prescribed drugs by generics. In the case of antiepileptic drugs (AED), which are characterised by a scant therapeutic margin, these steps have sparked a scientific debate about their repercussion on the control of epileptic patients. We propose to draw up a set of implicit evidence-based consensus practice guidelines concerning issues related with this topic. A selective search for quality scientific information on the subject was conducted on PubMed-Medline, Tripdatabase and the Biblioteca Cochrane Plus. The selected references were analysed and discussed by the authors, and the recommendations deriving from them were collected. A total of 21 primary documents and 16 practice guidelines, protocols or experts' recommendations were identified. Our recommendations were explicitly included at the end of the text. The Andalusian Epilepsy Society makes the following recommendations: 1) not replacing an innovative AED by its generic in a controlled patient; 2) beginning treatment with a generic AED in monotherapy or in association is acceptable; 3) not exchanging generic AED from different pharmaceutical companies; 4) explaining to the patient the rules governing the authorization of generics and the importance of avoiding exchanges between different generic AED; and 5) if there is some worsening of the clinical condition or side effects appear following the introduction of a generic, the causes must be investigated and communicated to the bodies responsible for pharmacovigilance.

Risks and Benefits of Generic Antiepileptic Drugs

In most therapeutic areas, prescribing generic drugs seems to lower costs without sacrificing efficacy. The use of generic drugs for treating epilepsy may, however, be more controversial. A systematic review of the literature on generic antiepileptic drugs has been carried out based primarily on a bibliographical search in the Medline database. Published studies are usually of a descriptive nature and are sometimes based on generic drugs that were approved in times when regulatory agency requirements were not as strict as they are now. Experts claim that a change in pharmaceutical formulations could cause seizure recurrence in cases that had been successfully controlled in the past, with severe effects on patients. Meanwhile, several health organizations have provided inconsistent recommendations on the use of generic antiepileptic drugs. In order to obtain scientific evidence on the potential risks and benefits of interchanging branded and generic antiepileptic drugs, high methodological comparative studies are necessary. These studies could bring consensus about the role of generic drugs for treating epilepsy.

Patient perception of generic antiepileptic drugs in the Midwestern United States

Concerns have been raised about the safety of switching from a branded antiepileptic drug (AED) to a generic AED. The goal of the study described here was to understand patients' experiences with generic AEDs in the Midwestern United States. A one-page, six-item survey was mailed to 356 patients to determine patients' awareness of the existence and their usage of generic AEDs. Twenty-eight percent (27.8%) of respondents (N=179) reported breakthrough seizures they believed were a direct result of the switch from a brand to a generic AED, and 33.7% reported side effects due to the switch. Thirty-one percent (31.2%) returned to a brand-name AED as a result. Sixty-nine percent (68.8%) reported being unaware that some pharmacies switch to generic AEDs without a patient's or physician's consent, and 78.7% expressed concern over this. A significant percentage of patients reported that generic AEDs were responsible for breakthrough seizures and increased side effects. A significant percentage of patients also reported switching back to a brand-name AED and expressed concern over pharmacies switching to generic AEDs without a patient's or physician's consent.

The use of generic medication in epilepsy: A review of potential issues and challenges

Changing from brand name to generic antiepileptic drugs (AEDs) is increasingly being advocated by the authorities, principally for budgetary reasons. However, caution should be exercised since AEDs may have a narrow therapeutic margin, the regimen with AEDs may be complex, the consequences of uncontrolled seizures may be severe, and risk of side effects is relatively high, particularly when seizures are difficult to control. This article focuses on the possible problems that can arise from the substitution of AEDs formulations, such as loss of seizure control and emergence of new side effects. We would advise that patients stay on the same formulation of the first AED, whether a brand name or generic AED. Switching AED formulations should always be done with the necessary caution and under the physician's supervision. Closer follow-up during the transitional period is necessary, and dosage adjustment may be required. The patient should be given full and correct advice about risks involved in switching AED formulations.

Generic substitution in the treatment of epilepsy: Patient and physician perceptions

Generic substitution of branded antiepileptic drugs (AEDs) has sparked recent debates. We sought to understand perceptions about generic AED substitution and how these guide prescribing. Surveys were conducted among 550 adult patients with self-reported epilepsy and 606 physicians who treat patients with epilepsy. Physicians (88%) were concerned about an increase in breakthrough seizures in patients switched from a brand AED to a generic or among generics. Two-thirds of physicians and 34% of patients have linked breakthrough seizures to generic AED substitution. Physicians (75%) and patients (65%) were also concerned about efficacy. About half of physicians were extremely/very likely to request that brand AEDs not be substituted with a generic. In conclusion, perceptions among physicians and patients do not align with the FDA position that generic AEDs have the same clinical effect and safety profile as branded AEDs. Additional investigation on bioequivalence may help address ongoing concerns and inform policy-making decisions.

Generic antiepileptic drugs: current controversies and future directions.

The Food and Drug Administration requires rigorous testing of generic formulations of antiepileptic drugs to assure bioequivalence to the brand product and asserts that all approved formulations are interchangeable. Physician surveys, case reports, and "switchback" rates from large-scale generic conversions imply that all generic formulations may not be equal to the brand drug for all patient groups. This review presents the current state of the data on bioequivalence and therapeutic equivalence and proposes a series of studies to better clarify the risks of generic formulation substitution in susceptible populations. Until such studies are completed, when switching to generic formulations, health-care providers and people with epilepsy would do well to proceed cautiously and understand the potential risks and benefits of substitution. Extra caution may be needed for patients at highest risk of seizure complications, such as the pregnant patient, patients with recurrent status epilepticus, or patients who have been seizure-free for long periods of time and are driving.

Generic substitution in the treatment of epilepsy

There are concerns that generic and brand antiepileptic drugs (AEDs) may not be therapeutically equivalent. This study investigated how generic AED substitution may have negative consequences. Sixty-nine of 150 physicians who participated in a large survey on generic AED substitution completed a case review form regarding a patient who experienced a loss of seizure control due to a generic AED. Nineteen were excluded from analysis. Fifty patients, well-controlled on a brand AED, subsequently experienced a breakthrough seizure or increased seizure frequency after switching to a generic without other provoking factors. AEDs included phenytoin (15 cases), valproic acid (14), carbamazepine (7), gabapentin (8), and zonisamide (8). Two patients were on a combination of two AEDs, both of which were switched to generics. In 26 cases serum AED levels were known both before and after generic substitution. Twenty-one had lower levels at the time of the breakthrough seizure on the generic medication. Loss of seizure control had a negative impact on quality of life, including loss of driving privileges (n = 30) and missed school/work days (n = 9). Changing from a brand antiepileptic drug (AED) to a generic may result in seizures. This raises the concern that current Food and Drug therapeutic equivalence testing regulations may not be adequate for AEDs and suggests that more clinical evidence is needed. Physicians, pharmacists, patients, and policy makers should be aware that for some patients there may be risks associated with switching from brand to generic AEDs.

Generic antiepileptic drugs

Generic antiepileptic drugs (AEDs) generally provide safe, effective, lower-cost alternatives to brand-name drugs. To be approved by the US Food and Drug Administration (FDA), manufacturers must show that generic drugs are comparable to brand-name formulations, meeting bioequivalence, dissolution, and manufacturing quality standards. Bioequivalence for most generic formulations is evaluated by measuring blood pharmacokinetic values in a small, crossover study of adult volunteers taking single doses of brand-name and generic AEDs. Bioequivalence standards require that ratios of average peak drug concentrations (C(max)) and total extent of absorption (area under the curve, AUC) for a test drug be within 80% to 125% of the reference brand-name drug, with a confidence interval of 90%. Bioequivalence of most generic AEDs, however, has not been evaluated in patients with epilepsy or in other special populations such as elderly patients or patients taking multiple AEDs and prodrugs. Moreover, evidence is limited regarding the adequacy of FDA generic standards for AEDs, particularly for "narrow therapeutic ratio" medications such as oxcarbazepine, although two carbamazepine studies are supportive. Most patients can successfully initiate therapy with generic AEDs and can safely switch from brand-name to generic AEDs (and sometimes back again). The FDA, however, has not shown safety in generic-to-generic switches, which could potentially cause drug concentration changes of up to 40%. Less expensive generic formulations will soon be available for most of the "second generation" AEDs--onisamide, for example, recently had 17 generic formulations approved in the United States--providing substantial savings in health care costs. In summary, although generic AEDs are generally safe and effective for most patients, the current bioequivalence standards may not be sufficient for certain patient populations and for certain drugs, requiring vulnerable patients to be monitored very carefully when converting to generic AEDs. The adequacy or inadequacy of FDA bioequivalence standards for AEDs has not yet been well evaluated with large, well-controlled studies.

Switching from branded to generic antiepileptic drugs as a confounding factor and unpredictable diagnostic pitfall in epilepsy management

Switching from branded to generic antiepileptic drugs as a confounding factor and unpredictable diagnostic pitfall in epilepsy management

POSITION STATEMENT ON THE COVERAGE OF ANTICONVULSANT DRUGS FOR THE TREATMENT OF EPILEPSY

We read with concern the position statement1 and editorial2 on generic substitution of antiepileptic drugs (AEDs). The American Epilepsy Society and the Epilepsy Foundation are also studying generic substitution and legislation restricting generic prescription is being considered throughout the United States. These efforts are surprising since there is scant published evidence of problems with current generic AED formulations, and generic versions of many newer AEDs have yet to be released. While problems have been noted with older generic formulations of poorly water-soluble AEDs such as phenytoin, generic versions of newer, highly soluble AEDs such as gabapentin, zonisamide, lamotrigine, topiramate, and levetiracetam are unlikely to have similar problems.3 Nonetheless, hard evidence is absent. We feel that prospective, blinded, randomized trials—not anecdotal opinion surveys—are required to address a highly concrete, quantifiable subject: whether generic AEDs achieve significantly different serum levels than brand versions. Despite the paucity of data, legislation has been proposed in Washington State (HB 2123)4 among others, which would impede prescription of generic AEDs by requiring providers and patients to separately consent to their dispensing. This will diminish the use of generics by allowing patients to opt out of generic substitution when the prescription is filled, and by confronting providers with additional paperwork. These barriers to generic competition will only increase prescription drug costs, both for the patient who pays out of pocket and for third-party and government health care payers. This is not in the patient’s best interest. We also need to acknowledge the significant financial forces that may influence the debate. Brand name AEDs each generate hundreds of millions of dollars annually in revenue for the manufacturer, and this revenue typically drops by 80 to 90% in the first year after generic versions are introduced. Thus, the pharmaceutical industry has a vested interest in …

Generic Products of Antiepileptic Drugs (AEDs): Is It an Issue?

The availability of generic products of antiepileptic drugs (AEDs) has raised the following concerns: (1) Do generic AEDs work as well as brand AEDs in terms of their efficacy, safety and quality? (2) Can generic AEDs be used as substitutions for brand AEDs? and (3) Can generic products of AEDs be used interchangeably? The traditional average bioequivalence analysis addresses concern 1 but does not provide a complete adequate response to concerns 2 and 3. Drug interchangeability can be classified as drug prescribability or drug switchability. Drug prescribability refers to the situation where a patient is treated for the first time so that either a brand or a bioequivalent generic AED can be chosen. Drug switchability refers to the situation in which a brand AED is switched to a bioequivalent generic product of the same AED. The traditional average bioequivalence approach is sufficient to evaluate the prescribability of generic products, but does not ensure the switchability between prescribable formulations. The necessity of assuring switchability of two formulations can be addressed by individual bioequivalence. While the switch to generic AEDs is well tolerated by many patients and in general cost-effective, seizure control should not be sacrificed on the basis of cost alone, as the major end point in treating epilepsy with AEDs is seizure control without side effects. Until we have individual (within patient) bioequivalence data on generic AEDs and/or the tools to a priori identify the subset of patients susceptible to the generic switch, a switch of AED products in seizure-free patients is not recommended.