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

Purpose: The 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. / Methods: A 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. / Results: Patients had epilepsy for a mean period of 14.1 ± 10.6 years and the mean daily LEV dose was 2583.3 ± 763.7 mg. The mean AUC ± SD and Cmax ± SD was 288.4 ± 86.3 (mg/L) h and 37.8 ± 10.4 mg/L respectively for brand LEV and 319.2 ± 104.7 (mg/L) h and 41.6 ± 12.3 mg/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. / Conclusions: In 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

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

Purpose The 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. Methods A 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. Results Patients had epilepsy for a mean period of 14.1 ± 10.6 years and the mean daily LEV dose was 2583.3 ± 763.7 mg. The mean AUC ± SD and Cmax ± SD was 288.4 ± 86.3 (mg/L) h and 37.8 ± 10.4 mg/L respectively for brand LEV and 319.2 ± 104.7 (mg/L) h and 41.6 ± 12.3 mg/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. Conclusions In 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. © 2017 British Epilepsy Associatio

Associations of ESR2 AluI (G/A) polymorphism with ischemic stroke in Caucasians

Raising interest towards genes implicates the effect of estrogen receptor-alpha (ESR1) gene on cerebrovascular disease, but data are lacking regarding the effect of estrogen receptor-beta (ESR2) gene. We assessed the hypothesis that AluI (G/A) polymorphism of the ESR2 gene (rs 4986938) is associated with ischemic stroke in a Caucasian population. Four hundred twenty four consecutive stroke patients and 430 age and gender-matched controls were enrolled in three stroke centers in Greece over one-year period. Patients and controls were compared in regard to the prevalence of the aforementioned polymorphism. No association was found between variations in the ESR2 gene and risk of stroke or stroke subtype in men and women. Of note, a gender-specific association of G allele with the onset of stroke at a younger age in male patients was found (63.68 ± 12.687 years in G allele (GG + AG) carriers vs. 68.95 ± 10.757 years in non-carriers (AA), p = 0.008). Further population independent studies are needed to establish the role of ESR2 gene polymorphisms in relation to ischemic stroke in both genders. Such studies could lead to ERβ agonists being validated in individuals with certain genotypes and/or alleles towards the development of efficient strategies to preventing ischemic stroke in both men and women. © 2012 Elsevier B.V. All rights reserved

Apolipoprotein E polymorphisms and ischaemic stroke: a two-center Greek study

Background and purpose: Apolipropotein E(apoE) is a plasma protein exhibiting three common isoforms (E2, E3, E4). Its involvement in lipoprotein metabolism may have an impact on stroke occurrence. As results in the literature are inconclusive further studies are needed to elucidate its role. Our objective was to study the role of apoE isoforms and the interplay with environmental risk factors in patients with first ischaemic stroke occurrence in the Greek population. Methods: Three hundred and twenty-nine patients with first-ever ischaemic stroke were included in our study. Strokes of cardioembolic origin and patients with autoimmune or prothrombotic syndromes were excluded. A control group of 361 subjects with no stroke history were also included in our study. Risk factors (hyperlipidemia, hypertension, diabetes mellitus and smoking) were assessed. ApoE alleles were determined in all subjects participating in the study. Results: Genotype epsilon 3/epsilon 3 was found to have a protective role against stroke occurrence compared with other genotypes (odds ratio 0.674, 95% confidence interval 0.480-0.946) especially in the female patient subgroup. In multivariate analysis after adjustment for age, body mass index (BMI), hypertension, dyslipidemia, diabetes mellitus and smoking, the role of genotype was limited and outweighed by risk factors in both genders. No association between apoE alleles and BMI, cholesterol, triglycerides or high-density lipoprotein plasma levels was noted. Conclusions: Our study was indicative of a protective role of the epsilon 3/epsilon 3 genotype, especially in female patients. However, risk factors such as age, BMI, hypertension, dyslipidemia, diabetes mellitus and smoking have a strong impact on stroke occurrence and outweigh the protective role of the epsilon 3/epsilon 3 genotype