Generic Antiepileptic Drugs Research Articles

Generic Modified-Release Antiepileptic Drugs: No Difference Within Formulations, but Important Differences Across Formulations.

Generic Modified-Release Antiepileptic Drugs: No Difference Within Formulations, but Important Differences Across Formulations.

Does substitution of brand name medications by generics differ between pharmacotherapeutic classes? A population-based cohort study in France.

The purpose of this study was to measure the rate of substitution failure to generic antiepileptic drugs (AEDs) compared to two other pharmacotherapeutic classes (neuroleptics, beta-blockers). We conducted a cohort study involving beneficiaries of the French health insurance system from January 2009 to November 2012. Substitution failure to generic drugs was estimated by the rate of switchback (i.e. from generic drug back to its branded drug). We selected the patients who had a dispensation of a branded AED for 60days or more during the 90days preceding the generic substitution. Cox proportional hazard regression was used to model time to switchback for antiepileptics vs. other therapeutic classes in the 90days after generic substitution, adjusting for age, gender and polytherapy. The cohort included 6727 patients of whom 1947 were exposed to AEDs, 2398 to neuroleptics and 2382 to beta-blockers. The switchback rate was 62% for AEDs. AED users were more likely to switch back as compared to beta-blocker (crude hazard ratio 1.87; 95% CI 1.68-2.07 for patients under 75) or neuroleptic users. The same observation was made in patients above 75years (crude hazard ratio 1.36; 95% CI 1.16-1.60). Compared to beta-blocker users, AED users were more likely to switch back to the branded drug, whereas this difference was not observed with neuroleptics. These results could reflect a poor acceptance of switching AEDs to generic compounds in France.

Switching generic antiepileptic drug manufacturer not linked to seizures: A case-crossover study.

With more antiepileptic drugs (AED) becoming available in generic form, we estimated the risk of seizure-related events associated with refilling generic AEDs and the effect of switching between different manufacturers of the same generic drug. We designed a population-based case-crossover study using the Medicaid Analytic eXtract and a US commercial health insurance database. We identified 83,001 generic AED users who experienced a seizure-related hospital admission or emergency room visit between 2000 and 2013 and assessed whether they received a refill of the same AED from the same manufacturer or a different manufacturer. Patients served as their own controls and conditional logistic regression was used to compare exposure to a refill during the hazard period, defined as days 2-36 preceding the seizure-related event, to exposure during the control period, defined as days 51-85 preceding the seizure-related event. Generic AED refilling was associated with an 8% increase in the odds of seizure-related events (odds ratio [OR] 1.08; 95% confidence interval [CI] 1.06-1.11). The OR following a switch to a different manufacturer of the same AED was 1.09 (95% CI 1.03-1.15); however, after adjusting for the process of refilling, there was no association between switching and seizure-related hospital visits (OR 1.00; 95% CI 0.94-1.07). Among patients on a generic AED, refilling the same AED was associated with an elevated risk of seizure-related event; however, there was no additional risk from switching during that refill to a different manufacturer. Generic AEDs available to US patients, with Food and Drug Administration-validated bioequivalence, appear to be safe clinical choices.

Assessing bioequivalence of generic modified-release antiepileptic drugs.

In the article “Assessing bioequivalence of generic modified-release antiepileptic drugs” by E.L. Johnson et al.,1 there is an error in figure 2, panels A and B (depicting …

Nonadherence to antiepileptic drugs in Germany: A retrospective, population-based study.

To assess the effect of patient and drug characteristics on medication adherence in people with epilepsy (PWE) in a large cohort representative of the German population. Information was obtained from the Disease Analyzer database that collects anonymous demographic and medical data from practice computer systems throughout Germany. From 2010 to 2013, adult PWE were retrospectively analyzed regarding demographic characteristics, comorbidities, and treatment with antiepileptic drugs (AED). Adherence was measured using the medication possession ratio (MPR). Individuals with an MPR <80% were classified as nonadherent. Multivariate regression models were applied to assess the association of different factors with adherence by calculating adjusted odds ratios (OR) with 95% confidence intervals. A total of 31,317 PWE were included. The mean MPR was 81.1% (SD 25.7%) with 64.7% of patients showing good adherence (MPR >80%). Patient-related factors associated with good adherence to AED treatment were West German residence (OR 1.23, p < 0.0001) and learning disability (OR 1.80, p < 0.0001). Adherence was higher in patients treated with new than old (OR 1.52, p < 0.0001) and branded than generic AED (OR 1.44, p < 0.0001). Among the most common AED, levetiracetam achieved best adherence (OR 2.85, p < 0.0001), valproate lowest. Two or more daily dosages reduced adherence (TID vs QD: OR 0.84, p = 0.005; BID vs QD: OR 0.86, p = 0.011). One third of PWE treated with AED in Germany showed poor adherence, which was related to demographic characteristics and drug properties. Administration of new, well-tolerated drugs in simple dosage regimens improved AED compliance.

Potential problems and recommendations regarding substitution of generic antiepileptic drugs: a systematic review of literature.

Despite the availability of generic antiepileptic drugs (AEDs), still patients and neurologists hesitate to make a switch due to assorted reasons. The objectives of this review were to evaluate the risks associated with the generic substitution of AEDs. In this context, we also summarized the recommendations of various international societies to treat epileptic patients. We used a number of electronic databases to identify the relevant published studies which demonstrated the potential problems and recommendations regarding generic substitution of AEDs. Of 204 articles found initially, 153 were selected for additional review. Subsequently, 68 articles were finally selected. This review concluded that potential problems linked with the generic substitution of AEDs could be bioequivalence issues, failure of drug therapy, emergence of adverse events and increase in the frequency of seizures. The reasons could be the pharmacokinetics properties of AEDs and unique characteristics of some epilepsy patients. Consequently, the generic substitution of AEDs affects the successful treatment and quality of life of the patients. Various guidelines recommend the well-controlled epileptic patients to avoid switching from brand-to-generic products, generic-to-brand products or generic to some other generic products.

Generic-to-generic lamotrigine switches in people with epilepsy: the randomised controlled EQUIGEN trial

Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy. The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200-800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, "high" vs "low"), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80-125%) in the analysis population. This study is registered with ClinicalTrials.gov\, number NCT01713777. Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98-103, Cmax 90% CI 99-105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study. Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate. American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration.

No difference in efficacy between generic antiepileptic drugs

No difference in efficacy between generic antiepileptic drugs

PROBLEMS OF THE INTERCHANGEBILITY OF ANTIEPILEPTIC DRUGS: EFFICACY AND SAFETY OF VALPROATES

The problem of interchangeability of original and generic antiepileptic drugs is considered. In particular, the safety of interchangeability of valproic acid containing drugs with different trade names is discussed. The analysis of 216 spontaneous reports in the national database from 2009 to 2014, containing information about the problem that occurs when you change the drug, was done. The overall structure of adverse reactions and their distribution to system organ classes were evaluated, the clinical cases were described. Also our aim was to consider separately the different options of substitution: original drugs – generics, and vice versa, two generics and different drug forms of the same drug. Our results have shown that most problems occur while trying to interchange original to generic, and very often it require the return to the initial therapy.

Generic versus branded antiepileptic drug monotherapy for epilepsy

Generic versus branded antiepileptic drug monotherapy for epilepsy

Epilepsy care in the southern Caribbean.

Very little has been reported about the health resources available for patients with epilepsy in the five English-speaking southern Caribbean countries of Trinidad and Tobago, Barbados, Grenada, Saint Vincent and the Grenadines, and Saint Lucia. There is no comprehensive resource describing their health systems, access to specialty care, antiepileptic drug (AED) use, and availability of brain imaging and EEG. The purpose of this study was to profile epilepsy care in these countries as an initial step toward improving the standard of care and identifying gaps in care to guide future policy changes. In each southern Caribbean country, we conducted study visits and interviewed health-care providers, government health ministers, pharmacy directors, hospital medical directors, pharmacists, clinic staff, radiologists, and radiology and EEG technicians. Health-care providers completed extensive epilepsy care surveys. The five countries all have integrated government health systems with clinics and hospitals that provide free or heavily subsidized care and AEDs for patients with epilepsy. Only Trinidad and Tobago and Barbados, however, have neurology specialists. The three smaller countries lack government imaging and EEG facilities. Trinidad had up to one-year waits for public MRI/EEG. Government formularies in Grenada, Saint Vincent and the Grenadines, and Saint Lucia are limited to first-generation AEDs. One or more second-line agents are formulary in Trinidad and Barbados. Nonformulary drugs may be obtained for individual patients in Barbados. Grenada, Saint Lucia, and Saint Vincent and the Grenadines participate in an Organization of Eastern Caribbean States formulary purchasing system, which added levetiracetam following the survey. Newer generic AED formulations with the lowest risks for pregnancy malformation were not in use. In conclusion, patients with epilepsy in the southern Caribbean have excellent access to government clinics and hospitals, but AED choices are limited. Local medical providers reported that the major limitations in care were lack of specialty care, lack of imaging and EEG services, financial barriers to care, long wait times for care, and limited access to additional AEDs.

Generic lamotrigine versus brand-name Lamictal bioequivalence in patients with epilepsy: A field test of the FDA bioequivalence standard.

To test the current U.S. Food and Drug Administration (FDA) bioequivalence standard in a comparison of generic and brand-name drug pharmacokinetic (PK) performance in "generic-brittle" patients with epilepsy under clinical use conditions. This randomized, double-blind, multiple-dose, steady-state, fully replicated bioequivalence study compared generic lamotrigine to brand-name Lamictal in "generic-brittle" patients with epilepsy (n = 34) who were already taking lamotrigine. Patients were repeatedly switched between masked Lamictal and generic lamotrigine. Intensive PK blood sampling at the end of each 2-week treatment period yielded two 12-h PK profiles for brand-name and generic forms for each patient. Steady-state area under the curve (AUC), peak plasma concentration (Cmax ), and minimum plasma concentration (Cmin ) data were subjected to conventional average bioequivalence (ABE) analysis, reference-scaled ABE analysis, and within-subject variability (WSV) comparisons. In addition, generic-versus-brand comparisons in individual patients were performed. Secondary clinical outcomes included seizure frequency and adverse events. Generic demonstrated bioequivalence to brand. The 90% confidence intervals of the mean for steady-state AUC, Cmax , and Cmin for generic-versus-brand were 97.2-101.6%, 98.8-104.5%, and 93.4-101.0%, respectively. The WSV of generic and brand were also similar. Individual patient PK ratios for generic-versus-brand were similar but not identical, in part because brand-versus-brand profiles were not identical, even though subjects were rechallenged with the same product. Few subjects had seizure exacerbations or tolerability issues with product switching. One subject, however, reported 267 focal motor seizures, primarily on generic, although his brand and generic PK profiles were practically identical. Some neurologists question whether bioequivalence in healthy volunteers ensures therapeutic equivalence of brand and generic antiepileptic drugs in patients with epilepsy, who may be at increased risk for problems with brand-to-generic switching. Bioequivalence results in "generic-brittle" patients with epilepsy under clinical conditions support the soundness of the FDA bioequivalence standards. Adverse events on generic were not related to the small, allowable PK differences between generic and brand.

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

The benefits of antiepileptic drug (AED) blood level monitoring to complement clinical management of people with epilepsy

IntroductionSome argue that there is no evidence to support the use of antiepileptic drug (AED) blood level monitoring when treating people with epilepsy (PWE). This paper identifies how AED monitoring can be invaluable in such treatment. Specific examples(i)Compliance: Antiepileptic drug blood levels often confirm noncompliance rather than adequate seizure control, confirming subtherapeutic levels in PWE attending hospitals due to seizures. Routine monitoring of AED levels may prevent breakthrough seizures by identifying noncompliance and instituting heightened compliance measures before experiencing breakthrough seizures without modifying dosages. For PWE attending hospitals due to seizures, loading with the AED shown to be subtherapeutic may be all that is required.(ii)Cluster seizures and status epilepticus: When using long-acting AEDs to complement benzodiazepines, blood level monitoring confirms that an adequate dosage was given and, if not, a further bolus can be administered with further monitoring. This is particularly useful when using rectal administration of AEDs.(iii)Polypharmacy: Polypharmacy provokes drug interactions in which case AED monitoring helps in differentiating adequate dosing, offending AED with toxicity and free level measuring benefits when total levels are unhelpful.(iv)Generic substitution: Generic AEDs can fluctuate considerably from a parent compound, and even a parent compound, sourced from an alternative supplier, may have altered bioavailability for which blood level monitoring is very useful. ConclusionsWhile therapeutic blood level monitoring is not a substitute for good clinical judgment, it offers a valuable adjunct to patient care.

Switching between phenytoin generics in patients with epilepsy may lead to increased risk of breakthrough seizure: chart analysis and practice recommendations.

The Food and Drug Administration (FDA) only requires bioequivalence testing of generic substitutions in order for them to be deemed equivalen to the original product. There may be a large difference of bioavailability among the generic drugs that especially have a narrow therapeutic index, and this may affect clinical outcomes. We aimed to determine whether switching from generic-to-generic equivalent anti-epileptic drugs (AEDs) in patients with epilepsy is associated with clinical outcomes. We performed a retrospective study using the electronic medical records of a tertiary hospital. Adults with a history of epilepsy who used a generic phenytoin and whose therapy was switched to another generic phenytoin between January 2012 and June 2013 were included (n = 80). We compared the drug concentration of phenytoin and seizure events before and after the switch. After switching their generic phenytoin, 33 out of 80 patients (41%) suffered from increasing seizure events (pre-interchange period, 0.44 ± 0.97; post-interchange period, 1.24 ± 2.05; p < 0.0001). The number of medical visits for acute seizure significantly increased in the post-interchange period. The phenytoin serum concentration of all the patients was lesser in the post-interchange period than in the pre-interchange period. (pre-interchange period, 12.79 μg/mL; post-interchange period, 6.36 μg/mL; p < 0.0001). Among the patients with drug resistant epilepsy (DRE), 17 patients (84.2%) had increasing seizure events in the post-interchange period. We confirmed that there was a significant difference in bioavailability between generic phenytoin. Therefore, when using or switching generic anti-epileptic drugs, therapeutic drug monitoring must be done, and the patients' condition must be considered.

Assessing bioequivalence of antiepileptic drugs: are the current requirements too permissive?

In order to evaluate the permissiveness of current bioequivalence requirements for antiepileptic drugs we investigated how accurate Cmax and AUC0-t of generic antiepileptic drugs approved in Brazil are in comparison to reference products. Data collected from assessment reports of approved bioequivalence studies archived in the Brazilian regulatory agency in 2007-2012 were: geometric mean ratios and 90% confidence intervals (CI) for Cmax and AUC0-t, intra-subject variability (CV) of Cmax and AUC0-t and number of subjects. The average difference in Cmax and AUC0-t between generic and reference products was 5% and 3%, respectively. Maximum deviation from 1.00 of the CI of Cmax can achieve 15-20% (demonstrated in 27% of studies); for AUC0-t, 25% of studies showed the deviation can be >10%. All studies that used adequate number of subjects for a 90% CI of 0.90-1.11 complied with it for AUC0-t, except one of carbamazepine, but only 33% complied with it for both AUC0-t and Cmax. The CV was strongly correlated to the maximum CI deviation for AUC0-t (CV of approximately 15% corresponding to deviation of 10%). Studies that presented maximum CI deviation ≤ 10 % together with CV ≤ 15% for AUC0-t represented 65% of the total. Weaker correlation was observed for Cmax and no correlation was seen between maximum CI deviation and number of subjects. Modification in legislation for bioequivalence of antiepileptic drugs is suggested, not only with constraint of AUC0-t 90% CI to 0.90-1.11, but also with limitation of the CV to 15%, as to assure similar variance in pharmacokinetics and diminish the risk of critical plasma-level fluctuation when switching between generic and reference formulations. Although most generics presented differences ≤ 10% in AUC0-t compared to their references, some narrow therapeutic index drugs displayed differences that could be clinically significant after product substitution.

Is switching from brand name to generic formulations of phenobarbital associated with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral formulations (Luminal® vet, Phenoleptil®) in dogs

BackgroundIn human medicine, adverse outcomes associated with switching between bioequivalent brand name and generic antiepileptic drug products is a subject of concern among clinicians. In veterinary medicine, epilepsy in dogs is usually treated with phenobarbital, either with the standard brand name formulation Luminal® or the veterinary products Luminal® vet and the generic formulation Phenoleptil®. Luminal® and Luminal® vet are identical 100 mg tablet formulations, while Phenoleptil® is available in the form of 12.5 and 50 mg tablets. Following approval of Phenoleptil® for treatment of canine epilepsy, it was repeatedly reported by clinicians and dog owners that switching from Luminal® (human tablets) to Phenoleptil® in epileptic dogs, which were controlled by treatment with Luminal®, induced recurrence of seizures. In the present study, we compared bioavailability of phenobarbital after single dose administration of Luminal® vet vs. Phenoleptil® with a crossover design in 8 healthy Beagle dogs. Both drugs were administered at a dose of 100 mg/dog, resulting in 8 mg/kg phenobarbital on average.ResultsPeak plasma concentrations (Cmax) following Luminal® vet vs. Phenoleptil® were about the same in most dogs (10.9 ± 0.92 vs. 10.5 ± 0.77 μg/ml), and only one dog showed noticeable lower concentrations after Phenoleptil® vs. Luminal® vet. Elimination half-life was about 50 h (50.3 ± 3.1 vs. 52.9 ± 2.8 h) without differences between the formulations. The relative bioavailability of the two products (Phenoleptil® vs. Luminal® vet.) was 0.98 ± 0.031, indicating that both formulations resulted in about the same bioavailability.ConclusionsOverall, the two formulations did not differ significantly with respect to pharmacokinetic parameters when mean group parameters were compared. Thus, the reasons for the anecdotal reports, if true, that switching from the brand to the generic formulation of phenobarbital may lead to recurrence of seizures are obviously not related to a generally lower bioavailability of the generic formulation, although single dogs may exhibit lower plasma levels after the generic formulation that could be clinically meaningful.

Generic Products of Antiepileptic Drugs: A Perspective on Bioequivalence, Bioavailability, and Formulation Switches Using Monte Carlo Simulations

Generic products of antiepileptic drugs (AEDs) are currently a controversial topic as neurologists and patients are reluctant to switch from brand products to generics and to switch between generics. The aim of this study was to provide enlightenment on issues of bioequivalence (BE) and interchangeability of AED products. Monte Carlo simulations of the classic 2 × 2 BE studies were performed to study the effect of sample size, within-subject variability, and the true difference in pharmacokinetic values of the products under comparison on BE acceptance of generic AED products. Simulations were extended to study the comparative performance of two generic AED products against the same innovative product. The simulated results are compared with literature data on AEDs. The question with regard to bioavailability (BA) is whether two formulations are different, while for BE the question is whether two formulations are sufficiently similar in terms of extent and rate of absorption. Therefore, the criteria for BA and BE and the statistical analysis involved in their analysis are different. Two generic formulations that meet regulatory approval requirements for generics by being bioequivalent to the same innovative AED may not be bioequivalent to one another and therefore should not be regarded as equal or as therapeutically equivalent products. A switch from a standard or an immediate-release formulation to a modified-release product, which comprises extended-release or delayed-release formulations, should not be regarded as a switch between generics, but rather as a switch between different formulation types. Switches between bioequivalent generic AED products could potentially lead to larger changes in plasma levels and exposure than the brand-to-generic switch. The simulation work verified the clinical findings that not all generic AED products bioequivalent to the same innovative product are bioequivalent to one another. Two generic formulations that meet regulatory approval requirements for generics, by being bioequivalent to the innovative AED, may not be bioequivalent to one another. Additional BE criteria are needed for a formulation switch, particularly in epilepsy, where a breakthrough seizure may change a patient's status from seizure-free to refractory.

Generic substitution of antiepileptic drugs — A survey of patients' perspectives in Germany and other German-speaking countries

In this study, we sought to determine the patients' attitudes towards generic substitution of antiepileptic drugs (AEDs) and their experiences with the usage of generic antiepileptic drugs in Germany and other German-speaking countries. A questionnaire was designed for a cross-sectional study. Two thousand copies of the questionnaire were delivered with a magazine edited by a patients' organization. Additionally, the questionnaire was placed on the internet platform of another patients' organization. Thirty-two percent of the patients who already experienced a switch to generic AEDs complained of problems with the switch. Patients who answered the magazine survey worried significantly more about generic substitution of AEDs than patients who answered the internet version. Patients who had never switched were more concerned about generic substitution than those who had already switched. Moreover, patients' beliefs differed between the use of generic drugs in acute medical conditions such as pain and infections and the use of generic AEDs in epilepsy.

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

There have been considerable debates about bioequivalence and generic substitution of certain critical care drugs. We aimed to understand patient attitudes and perceptions about generic substitution in the treatment of epilepsy. In this pilot study, a self-administered anonymous survey was completed by 47 patients with epilepsy. The response rate by postal mail was 6.7%. More than 70% of the patients were concerned about the effectiveness of generic antiepileptic drugs, and 68% of the patients were not comfortable receiving generics to treat their epilepsy. About 87% of the patients thought that their antiepileptic drug should only be substituted with a generic with their consent, and 64% of the patients believed that substitution should only take place with the consent of their doctor. Considerable concern exists among patients about generic substitution in the treatment of epilepsy. More data regarding whether generic antiepileptic drugs are bioequivalent in clinical situations would help to address patient concerns.