Generic Antiepileptic Drugs Research Articles

Correlation between prescription volumes of generic antiepileptic drugs and the number of clinical epileptologists across prefectural regions in Japan: A descriptive study using a national claims database

PurposeAlthough generic drugs are essential in reducing medical costs, their use in epilepsy therapy remains a subject of ongoing debate. In this study, we analysed prescription trends of generic drugs using data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. MethodsThe number of generic drug prescriptions from 2017–2021 was extracted from the NDB Open Data Japan, with data for each medication stratified by prefectural region, sex, and age, allowing for the analysis of the impact of each factor. We analysed the correlation between the prescription volumes of generic antiseizure medications (ASMs) and the number of clinical epileptologists registered with the Japan Epilepsy Society per 100,000 population. ResultsIn 2021, the prescription volume of generic ASMs was 49 %, whereas that for other pharmacological agents was between 70–80 %. Notably, for children < 15 years of age, generics made up approximately 20 % of prescriptions, which was significantly less than that in other age groups. Analysis by prefecture revealed a negative correlation between prescription volumes of ASMs and the number of clinical epileptologists across prefectural regions in Japan (R = −0.47, p < 0.01). ConclusionOur findings indicate that the higher the proportion of clinical epileptologists in each prefecture, the lower the number of prescribed generic ASMs. Clinical epileptologists in Japan therefore prescribe antiseizure agents in accordance with the Japanese epilepsy treatment guidelines that do not recommend the use of generic agents.

Lack of association between generic brittleness and neuropsychiatric measures in patients with epilepsy

PurposeIn a prior bioequivalence study, generic brittle (GB) patients with epilepsy who were considered at risk of worsened seizures or drug side effects from switching antiepileptic drug (AED) formulations demonstrated no significant difference in their drug levels when switched between a brand and generic AED. An alternative basis for being GB may relate to having a personality or mindset that predisposes to poor outcomes from a formulation switch. The objective of this study was to explore whether GB patients with epilepsy could be differentiated from not GB patients based on standardized measures of personality, mood, outlook, and beliefs. MethodsThis was an exploratory, observational, case-control, non-therapeutic study in patients with epilepsy. Patient interviews were conducted, and histories were collected, yielding each patient (n = 148) to be determined as GB or not GB. Eight neuropsychiatry tests were administered to n = 127 of these patients. Tests included Neuroticism Extraversion Openness Personality Inventory 3 (NEO-PI 3), Life Orientation Test-Revised (LOT-R), Quality of Life in Epilepsy Inventory-89 (QOLIE-89), Adverse Childhood Experiences Score (ACE), Physical Symptoms Questionnaire or Patient Health Questionnaire-15 (PHQ-15), Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), and the Beliefs About Medicines Questionnaire Epilepsy (BMQ-Epilepsy). A total of 23 Chi squared analyses, along with logistical regression, were performed to assess which tests and sub-elements associated with GB status. ResultsNone of the neuropsychiatry tests or their sub-elements differentiated GB patients from not GB patients. Results implicate that standardized measures of personality, mood, outlook, and beliefs about their healthcare do not differ between GB and not GB patients with epilepsy, possibly because generic brittleness is caused by factors that neuropsychiatry tests do not measure. ConclusionsWe hypothesized that being GB may relate to having a personality or mindset that predisposes patients to attributing poor outcomes to a formulation switch. However, findings here in patients with epilepsy did not uncover neuropsychiatric factors that predict which patients were GB and which were not GB.

Comparing real-life carbamazepine exposure between innovator and generic formulation

Carbamazepine is an anticonvulsant largely used in the treatment of epilepsy. The use of generic antiepileptic drugs (AEDs) is controversial because of the eventual possibility to loss seizures control. The aim of our study was to compare the concentration over dose ratio of two products containing carbamazepine, the innovator (Tégrétol®-NOVARTIS) and the generic (Taver®-MEDOCHEMIE). It is a retrospective study (2009-2016) including 32 patients treated with carbamazepine. Patients were treated initially by innovator then switched to generic or vice versa. All patients have at least one level of carbamazepine plasma concentration (C0) with the innovator or the generic formulation. Monitoring of carabamazepine was made using immunoassay method (ARCHITECT-ABOTT®). The mean age of our patients was 28.4 years and ranged from 2 to 55 years. The sex ratio M/F was 1.46. The mean ratio C0/dose for the innovator group was 0.723 (min/max: 0.017/1.73), and the mean ratio C0/dose for the generic group was also 0.607 (min/max: 0.064/1.68). There was no statistically significant difference between both groups (P=0.16). Our results confirm the difference between the innovator and the generic formulation of carbamazepine. So, switching from innovator to generic seems to be safe and exposure to carbamazepine remains the same.

Comparative Antiseizure Activities of Some Branded and Generic Antiepileptic Drugs in a Nigerian City

Branded antiepileptic drugs (AEDs) are expensive, and in developing countries, cheaper generic equivalents may be used interchangeably. Therefore, this study aimed to compare the antiseizure activities of some available branded and generic AEDs in mice. The physicochemical properties of four generic and branded AEDs (carbamazepine, CAB; sodium valproate, SVP; phenytoin, PHY, and phenobarbitone, PHB) were determined according to pharmacopoeial methods. The organoleptic proper-ties, tablet hardness and thickness of the samples were also assessed. The anticonvulsant effect of AEDs was determined using maximal electroshock (MES) and pentylenetetrazole (PTZ) induced seizure. The samples of AEDs showed uniformly comparable organoleptic properties. The active moiety content for all the samples fell within the acceptable ranges stipulated in the official compendia. A significant statistical difference (p≤0.05) in disintegration time existed between two generic formulations of PHB, PHB01 (4.62±1.17 min), and PHB02 (1.40±0.26 min). Similarly, a significant statistical difference (p≤0.05) in hardness (10.40±0.15 kgF vs 5.61±0.03 kgF) and disintegration time (4.65±0.49 min vs 0.64±0.30 min) was observed between the two brands of CAB (CAB02 and CAB03 respectively). No significant statistical difference exists in mean recovery time between control (5.70±0.72 min) and treatment groups (CAB01, 6.50±0.65 min) in the MEST. In the PTZ test, there was a significant (p≤0.001) difference in the mean onset of clonic spasm between control (10.03±0.75 min) and PHB, PHB01 (17.50±0.99 min) 30 min post-treatment. In conclusion, no significant variation in the physicochemical and antiseizure activity of branded and generic formulations of AEDs was observed

Medication Errors.

The article offers medical news briefs as of April 2021 A free COVID-19 vaccine handling toolkit for healthcare professionals was published by U S Pharmacopeia (USP) Hikma failed to include its warning on disposal on the bottle or outer carton of its Rufinamide oral suspension generic antiepileptic drug Also cited is the error in the labeling for the Piqray (alpelisib) kinase inhibitor drug

Generic versus branded antiepileptic drug monotherapy for epilepsy

Generic versus branded antiepileptic drug monotherapy for epilepsy

Continuity of specialized care upon transfer of adolescents with epilepsy from a pediatric to adult outpatient service

Introduction . One of the most serious periods in the treatment and follow-up of adolescent patients with early debut epilepsy is the transition to a medical center for adults. It is important to carefully watch any possible replacement of antiepileptic drugs (AEDs), which may affect the further course of epilepsy. Aim : to study the algorithms and procedures for bringing patients with epilepsy from a pediatric to adult outpatient practice, and also to evaluate the efficacy of therapy with synonymously replaced AEDs during this period. Materials and methods . A retrospective study involved 218 patients who were transferred from pediatric care to an adult outpatient network. The inclusion criteria were the presence of epilepsy diagnosed in childhood (before age of 18 years), continuous treatment with AEDs, age 18 through 20 years. The exclusion criteria were: irregular observations, failure to comply with medical prescriptions. In case of unplanned pregnancy or failure to take AEDs, the patient was excluded from the ongoing study. History, neurological status, EEG, video EEG monitoring and neuroimaging data were examined. The efficacy of AEDs was graded as “complete remission” (in the absence of epileptic seizures), “incomplete remission” (if the number of seizures dropped by 50% or more), and “without effect” (if the seizures continued). Two groups of patients were analyzed: those receiving original AEDs and those receiving generic AEDs. Results . The study showed that during the transition to an adult outpatient network, the specialized medical care continued: the young patients were monitored by epileptologists; at the same time, we noted a significant increase in the rate of replacement of original AEDs with the respective generics (54 patients). Of these patients, 25 individuals (46.3%) had recurrent seizures. Discussion . Maintaining the continuity of specialized medical care depends on the availability of the city center of epilepsy for children. In addition, the network of outpatient clinics for adult patients with epilepsy and other paroxysmal conditions should be organized in each administrative district. The procedure of synonymous AED replacement is regulated by medical and legal documents; thus, the drugs are prescribed according to their INNs, and pharmacies dispense the medicines under the same INNs but with the trade names that are currently available in the stock. According to reports, the seizures are controlled significantly better under therapy with original AEDs compared to generics. Conclusion . The present study demonstrates the relevance of medical care continuity during transition of young patients with epilepsy from a pediatric to adult outpatient network. However, more extensive comparative studies on the efficacy and safety of synonymous replacement of antiepileptic drugs with the same INNs are needed. All authors contributed equally to this article.

Effectiveness at 24 Months of Single-Source Generic Carbamazepine, Lamotrigine, or Levetiracetam in Newly Diagnosed Focal Epilepsy.

Kaiser Permanente advocates using single-source generics for brand-name drugs. We compared the effectiveness of 3 different-generation generic antiepileptic drugs (AEDs) in patients with focal epilepsies. To compare the effectiveness of the 3 most commonly used AEDs (carbamazepine [CBZ], lamotrigine [LTG], and levetiracetam [LEV]) after 24-month monotherapy. This is a retrospective data analysis of 646 consecutive AED-naive patients aged 1-88 years treated with CBZ, LTG, or LEV between 2006 and 2012 with dosing adjustments permitted during the first 6 months. Chi-squared test with p < 0.05 was used to calculate seizure-freedom and tolerability rates. At the end of the 24-month study period, 65.69% patients in the CBZ group continued to remain seizure free, 25.98% were drug failures, and 8.33% dropped out due to adverse events, with the corresponding numbers being 66.49%, 23.94%, and 9.57% in the LTG group and 72.44%, 12.99%, and 14.57% in the LEV group. Rash was the most common adverse event for CBZ (3.43%) and LTG (6.38%), and mood changes were the most commen adverse event for LEV (7.87%). Among the 3 groups (n = 646), AED tolerance rates and AED retention rates showed no significant difference (p = 0.08 and p = 0.23, respectively). Seizure-freedom rate difference among the 3 groups (n = 574) was significant (p = 0.003), and seizure-freedom rate for LEV was superior to CBZ (p = 0.001) and to LTG (p = 0.006). At the end of the 24-month study period, in a head-to-head comparison of single-source bioequivalent generic formulations, superior seizure-freedom rate and comparable tolerability and retention rates for LEV were observed when compared with CBZ and LTG.

PND72 EVOLUTION OF THE CONSUMPTION OF ANTIEPILETEC DRUGS IN MOROCCO FROM 2004 TO 2016

In 2015, the prevalence of epilepsy is estimated on about of 0.1% in the Moroccan general population. Whenever the disease remains unknown and patients are stigmatized or linked on spiritual beliefs. The Purpose of this study is to establish the profile and trend of evolution of antiepileptic drugs consumption. The system of classification ATC/DDD has been used as recommended by the WHO. The private data sales were extracted from IMS Health for Morocco and the hospital data were obtained from the ministry of health. The data initially expressed in unit of sales were then converted into DDD/1000inhab/Day. With a dozen of substances distributed in six classes ATC4, the private consumption of antiepileptic drugs is increasing (+61.35% in volume and 246.45% in value). The ‘’other antiepileptic class’’ show the important increasing (+4870% in volume), in addition to the fatty acid derivatives (+189%) and the carboxamides derivatives (+70%). Barbiturates recorded a low increasing (+2%). Benzodiazepines recorded a decreasing evolution (-84%). Only three substances (PHENOBARBITAL, VALPROIC ACID and CARBAMAZEPINE) have been tendered by the ministry of health at the hospital level. The general purchase increased for all substances, rising from 0.09DDD/1000inhab/Day in 2004 to 0.62DDD/1000inhab/Day in 2016. The public and private sector consumption shows predominance of private sector consumption but also the growing trend in public sector consumption (from 7% in 2004 to 25% in 2016). The three AED represent about 94% of the private consumption and the totality of public purchases The generics consumption progress since 2007 although it remains relatively low (14% in 2016). Considering the results of this work, the evolution of antiepileptic drugs consumption is largely linked to the consumption of the new antiepileptic drugs and to the consumption of generic antiepileptic drugs, especially coming from 2009.

Study of clinical efficacy, safety and tolerability of low cost branded generic antiepileptic drugs in children and adolescents

Background: Generic substitution is preferred to reduce healthcare costs and improve patient adherence. The review of literature showed that physicians all around the world were not comfortable in prescribing generic medications due to the lack of evidence on their safety and efficacy.Methods: A prospective study was conducted over a period of one year in Pune. The patients were categorized on their age and were assessed for the clinical effectiveness data (no. of breakthrough seizures and seizure free days) and safety data (no. of ADR episodes). The mean number of patients controlled and the frequency of adverse events at the 3rd and 6th month were calculated.Results: Authors assessed 150 newly diagnosed pediatric epileptic patients who received anti-epileptic drug monotherapy for at least 6 months, out of which 46 (30.66%) received Oxcarbazepine and 104 (69.33%) received Sodium Valproate. At the end of 3 months of therapy 140 (93.33%) patients were seizure free and 145 (96.66%) patients were seizure free at the end of 6 months. Adverse effects were observed in 14 (30.43) patients on oxcarbazepine and 26 (25%) patients on sodium valproate. The most common adverse effect was weight gain in 34 (22.66%) patients with both the AEDs.Conclusions: Seizure control was achieved in majority of the patients. In addition to the seizure control, the frequency of adverse effects was few and tolerable by the patients when prescribed with low cost branded generics.

New Anticonvulsants: Interchangeability Issues and the Use of Generic Anticonvulsants in Clinical Practice

This article looks into interchangeability and therapeutic equivalence of innovator and generic anticonvulsants — the first-generation and new antiepileptic drugs (AEDs). The results of a number of clinical trials assessing therapeutic equivalence of generic AEDs support the opinion that these medicines could only be substituted provided an ultra-cautious approach is used, even if the case involves only one International Nonproprietary Name, including, but not limited to different dosage forms of one and the same product. The aim of the study was to analyse factors leading to incorrect assessment of therapeutic equivalence of new and generic anticonvulsant drugs, and to improve methodological approaches to conducting clinical trials of these products. The paper cites data from Russian and foreign sources which state that the substitution of AEDs in some patients in full remission may result in adverse reactions or relapse of seizures. The analysis of the experience of scientific, expert, and regulatory institutions made it possible to develop a course of actions to be used when substituting AEDs and conducting clinical trials that assess therapeutic equivalence of new and generic anticonvulsants. The proposed methodology will help minimise potential health risks brought about by various factors that result in incorrect assessment of AEDs therapeutic equivalence and interchangeability.

Quality of life after switching to generic levetiracetam – A prospective comparative study

BackgroundImproved quality of life (QoL) is one of the most important objectives in the treatment of epilepsy. Recent prospective, clinical studies proved no significant differences between brand antiepileptic drugs (AEDs) and their generic equivalents in terms of seizure control, pharmacokinetics, or safety. In this study, we focused on possible changes in QoL and adverse events in connection with generic substitution of levetiracetam (LEV). MethodsThis was a prospective, naturalistic, two-cohort, twin-center study. After a baseline period of 10 weeks, outpatients with epilepsy on stable treatment with Keppra® either continued on this brand (reference group, n = 16) or switched to generic LEV (1A Pharma®) (study group, n = 16) for an eight-week study period. The Quality of Life in Epilepsy Inventory-31 (QOLIE-31) and an adverse events' questionnaire were administered at inclusion, after baseline, and at the end of the study period. The study protocol included a close clinical follow-up with repeated LEV serum concentration measurements and nurse-led outpatient visits. ResultsClinically relevant improvements in overall QOLIE-31 scores according to minimally important change (MIC) estimates were seen in both groups. QOLIE-31 subscales in both groups showed significantly less worry about seizures at the end of the study compared to scores at inclusion (study group: p = 0.01; reference group: p = 0.02). No significant deterioration in QoL or adverse events were observed following generic substitution. No switchbacks occurred. ConclusionsWe found reduced seizure worries over time among people with epilepsy allocated to either generic switch or continued treatment with brand LEV. We hypothesize that the nurse-led structured follow-up had an impact on seizure worries and switchback rates because of reduced nocebo effects. Further studies on generic AED substitution, focusing on psychological outcome measures, are warranted to test this supposition.

PMU64 THE IMPACT OF FORMULARY RESTRICTIONS ON LIKELIHOOD OF SUCCESSFUL DISPENSATION OF ANTIEPILEPTIC DRUG TREATMENT IN A PEDIATRIC PATIENT POPULATION

Formulary restrictions may have unintended consequences: delaying or reducing likelihood of antiepileptic drug (AED) therapy initiation. This has not been studied for pediatric patients with focal seizure (FS) prescribed AED therapy. This study assessed associations between formulary restriction and time to and likelihood of successful dispensation of prescribed AED treatment among pediatric patients with FS. Symphony Health’s Integrated Dataverse (IDV®) open-source claims data for 04/01/15–06/30/18 were used to identify patients with a diagnosis of FS and ≥1 new AED pharmacy claim, <18 years old, with ≥6 months of pharmacy data before and after. The index date was defined as earliest AED date that pharmacy claim was approved or rejected due to formulary restriction. Cohort assignment was also based on whether the index AED claim was approved or rejected due to formulary restriction. Proportion of patients with index AED dispensation and time to dispensation was analyzed during the 6-month follow-up period. The impact of formulary restriction on likelihood of prescribed AED’s successful dispensation was assessed using multivariable Cox proportional hazards model. There were 9,529 and 3,081 patients in the approved and rejected claim cohorts, respectively. The proportion of patients with an index claim for a generic AED was higher in the approved (95.9%) vs. the rejected (88.9%) cohort. Mean (SD) time to first dispensation was 2.1 (11.9) and 7.4 (21.5) days for the approved and rejected cohort, respectively. The proportion of patients with a successful index AED dispensation at 6 months was higher in the approved (92.8%) vs. rejected (75.7%) cohort. After adjustment, formulary-related rejection of an index AED was associated with lower likelihood of its successful dispensation [hazard ratio: 0.73; p<0.001]. Formulary restrictions may lead to an average delay of 5.3 days and reduced likelihood of successful dispensation of AED treatment for pediatric patients diagnosed with FS.

Generic substitutions of antiepileptic drugs: Is it possible to put an end to the discussion?

A policy on generic substitutions, which is aimed at reducing the cost-effectiveness of pharmacotherapy, was proposed by the WHO at the end of the 20th century; however, but the debate about their economic benefits has continued until now. There have been the most active discussions of whether an epileptic patient may be switched from brand-name to generic antiepileptic drugs. The paper gives data obtained in Russian and foreign studies of the therapeutic efficacy and safety of anticonvulsant generics versus their brand- name drugs, as well as the impact of generic substitutions on the cost-effectiveness of antiepileptic therapy. Emphasis is placed on the importance of the quality of generic medicines, their dosage forms, and regulatory requirements for registration of generics. The problem of generic instability is under discussion.

Risk-Based Bioequivalence Recommendations for Antiepileptic Drugs.

This review summarizes the current FDA practice in developing risk- and evidence-based product-specific bioequivalence guidances for antiepileptic drugs (AEDs). FDA's product-specific guidance (PSG) for AEDs takes into account the therapeutic index of each AED product. Several PSGs for AEDs recommend fully replicated studies and a reference-scaled average bioequivalence (RS-ABE) approach that permit the simultaneous equivalence comparison of the mean and within-subject variability of the test and reference products. The PSGs for AEDs published by FDA reflect the agency's current thinking on the bioequivalence studies and approval standards for generics of AEDs. Bioequivalence between brand and generic AED products demonstrated in controlled studies with epilepsy patients provides strong scientific support for the soundness of FDA bioequivalence standards.

Safety of switching from brand-name to generic levetiracetam in patients with epilepsy.

PurposeThe approach to the use of generic antiepileptic drugs has recently evolved from major concern to general acceptance, but the evidence related specifically to the safety of switching from brand-name to generic levetiracetam (LEV) is scarce. The aim of the study was to assess the risk of increased frequency of seizures or other adverse events after replacement of a brand-name LEV with a generic one.Patients and methodsThis retrospective analysis included 159 patients treated with LEV in a tertiary outpatient epilepsy clinic. We included all patients diagnosed with epilepsy who were treated with LEV as at March 1, 2013. Most patients were forced to switch to the generic LEV because of the sudden rise in cost of the branded LEV. We recorded data on age, sex, age at onset of epilepsy, type of epilepsy, and its treatment. We analyzed data from one visit before potential switching and from two visits after the potential switching. The interval between visits was typically 3 months. We registered an increase in the frequency of seizures and in the occurrence of adverse events.ResultsAmong 151 subjects who switched to generic LEV after March 1, 2013, increased frequency of seizures was noted in 9 patients (6%) during the first follow-up visit. Patients with increased frequency of seizures did not differ from other patients regarding sex, age, age at the onset of epilepsy, and the median dose of LEV before switching or the median duration of treatment with LEV before switching. Two patients returned to brand-name LEV. Adverse events were noted in six other patients (4%) and included somnolence, irritability, or dizziness.ConclusionSwitching from brand-name to generic LEV is generally safe.

Bioequivalence Between Generic and Branded Lamotrigine in People With Epilepsy

Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs. To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products. The Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (≥18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses. Participants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected. The primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%). Of the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57%) were men and 21 (43%) were women, 42 (86%) self-identified as white, and 46 (16) years was the mean (SD) age. The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC0-96, 96.9% and 101.9%). Replicate testing demonstrated no significant differences in within-subject variability across the 3 products (likelihood ratios, χ22 for log-transformed variables: AUC0-96, 2.58; Cmax, 0.64; and AUC0-∞, 4.05; P ≥ .13) and that the 3 products were also bioequivalent according to scaled ABE and individual bioequivalence criteria with no subject × formulation interaction (Cmax, 0.00; AUC0-96, 0.54; and AUC0-∞, 0.36; P ≥ .76). This study provides evidence that the disparate lamotrigine products studied are bioequivalent when tested in people with epilepsy taking concomitant antiepileptic drugs. clinicaltrials.gov Identifier: NCT01733394.

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)

ObjectiveDespite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. MethodsEvents reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. ResultsA total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. SignificanceSimilar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study.

Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting

PurposeThe therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. MethodsA prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4±16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. ResultsPatients had epilepsy for a mean period of 14.1±10.6years and the mean daily LEV dose was 2583.3±763.7mg. The mean AUC±SD and Cmax±SD was 288.4±86.3(mg/L)h and 37.8±10.4mg/L respectively for brand LEV and 319.2±104.7(mg/L)h and 41.6±12.3mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. ConclusionsIn our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV.

An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong.

New information about antiepileptic drugs has arisen since the publication of the Hong Kong Epilepsy Guideline in 2009. This article set out to fill the knowledge gap between 2007 and 2016 on the use of antiepileptic drugs in Hong Kong. Between May 2014 and April 2016, four consensus meetings were held in Hong Kong, where a group comprising 15 professionals (neurologists, paediatricians, neurosurgeons, radiologists, and clinical psychologists) from both public and private sectors aimed to review the best available evidence and update all practising physicians on a range of clinical issues including drug-related matters. All participants were council members of The Hong Kong Epilepsy Society. A literature review of the clinical use of antiepileptic drugs as monotherapy suggested Level A evidence for levetiracetam and Level B evidence for lacosamide. No change in the level of evidence was found for oxcarbazepine (Level A evidence) or pregabalin (undesignated), and no evidence was found for perampanel. A literature review on the clinical use of antiepileptic drugs as adjunctive therapy suggested Level A evidence for both lacosamide and perampanel. No change to the level of evidence was found for levetiracetam (Level A evidence), oxcarbazepine (Level A evidence), or pregabalin (Level A evidence). A literature search on the use of generic antiepileptic drugs suggested Level A evidence for the use of lamotrigine in generic substitution. Three lead authors of the Subcommittee drafted the manuscript that consisted of two parts-part A: evidence on new antiepileptic drugs, and part B: generic drugs. The recommendations on monotherapy/adjunctive therapy were presented during the meetings. The pros and cons for our health care system of generic substitution were discussed. The recommendations represent the 'general consensus' of the participants in keeping with the evidence found in the literature. Recommendations for the use of levetiracetam, lacosamide, oxcarbazepine, pregabalin, and perampanel were made. The consensus statements may provide a reference to physicians in their daily practice. Controversy exists over the use of generic products among patients who are currently taking brand medications. In this regard, approvals from prescriber and patient are pivotal. Good communication between doctors and patients is essential, as well as enlisting the assistance of doctors, nurses, and pharmacists, therapeutic blood monitoring if available, and the option of brand antiepileptic drug as a self-financed item. The physical appearance of generic drugs should be considered as it may hamper drug compliance. Support from medical services is recommended. In the longer term, the benefit of flexibility and the options to have a balance between the generic and brand drug market may need to be addressed by institutions and regulatory bodies.