Interchangeability among carbamazepine formulations: the impact over epilepsy patients

Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the "Interchangeable Pharmaceutical Product in the Treatment of Epilepsies" questionnaire was applied. The questionnaires "Adverse Events Profile" and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event "problems with skin" incresead (p=0.023) and "upset stomach" decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: "energy/fatigue" (p=0.048) and "total score" (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients' perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients' life.

Síndrome de sensibilidad a drogas con eosinofilia y síntomas sistémicos (DRESS) atípico por carbamazepina, a propósito de un caso pediátrico / Drug sensitivity syndrome with eosinophilia and atypical symptoms (DRESS) by carbamazepine: a case report

Introducción: El síndrome de sensibilidad a drogas con eosinofilia y síntomas sistémicos (DRESS) generalmente es acompañado por eosinofilia. Es una enfermedad que pone en peligro la vida del paciente. Se presenta como reacción adversa a infecciones y a medicamentos, usualmente asociada al uso de antiepilépticos. Caso clínico: Paciente de 6 años, masculino, con antecedente de Epilepsia de reciente diagnóstico, que consultó en Servicio de Urgencias dos semanas después de iniciar tratamiento con Carbamazepina, por cuadro caracterizado por eritema de predominio facial, exacerbado con la exposición al sol. Posteriormente presentó fiebre con episodios hasta 40 °C, que se asoció a convulsiones. Después de un exhaustivo estudio se concluyó DRESS atípico (sin eosinofilia), iniciando tratamiento corticoideo con favorable respuesta clínica. Discusión: El síndrome de DRESS, es una enfermedad de difícil diagnóstico por sus múltiples diagnósticos diferenciales y falta de criterios diagnósticos. Es esencial la suspensión inmediata del fármaco causante, para evitar progresión de la enfermedad e iniciar tratamiento precoz.

Background: The drug sensitivity syndrome with eosinophilia and systemic symptoms (DRESS) is usually accompanied by eosinophilia. It is a disease that endangers the life of the patient. It occurs as an adverse reaction to infections and medications, usually associated with the use of antiepileptics. Case report: A 6-year-old patient, male, with a recent diagnosis of epilepsy, who consulted the Emergency Department two weeks after initiating treatment with Carbamazepine because of a condition characterized by facial predominance erythema, exacerbated by sun exposition. Subsequently presented fever with episodes up to 40 ° C, which was associated with seizures. After an exhaustive study, atypical DRESS syndrome (without eosinophilia) was made, initiating corticoid treatment with favorable clinical response. Discussion: DRESS syndrome is a disease difficult to diagnose because of its multiple differential diagnoses and lack of diagnostic criteria. Immediate suspension of the causative drug is essential to prevent progression of the disease and initiate early treatment Keywords: Drug Hypersensitivity Syndrome, Carbamazepine, Corticoid.

Síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos debido a la carbamazepina: Caso pediátrico / Drug reaction with eosinophilia and systemic symptoms due to carbamazepine: Pediatric case

Entre las reacciones medicamentosas graves en la piel, se encuentran el síndrome de Stevens-Johnson, la necrólisis epidérmica tóxica y el síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos (drug reaction with eosinophilia and systemic symptoms; DRESS, por sus siglas en inglés), que son poco comunes en la población pediátrica (incidencia: 1/1000-10 000 niños), sin embargo, tienen mal pronóstico. El síndrome de sensibilidad a fármacos con eosinofilia y síntomas sistémicos consiste en erupciones cutáneas, alteraciones hematológicas, linfadenopatía y afectación de órganos. Se presenta el caso de un paciente masculino de 12 años que desarrolló esta patología después de iniciar el tratamiento anticonvulsivo con carbamazepina. Se considera que es importante que el personal de la salud tenga conocimiento de esta enfermedad para que sea incluida entre los diagnósticos diferenciales de pacientes con afecciones similares, ya que este síndrome es potencialmente mortal.

Severe skin reactions include Stevens-Johnson Syndrome, toxic epidermal necrolysis and Drug reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, which are uncommon in the pediatric population (incidence 1/1000-10 000 children), but they have bad prognosis. Drug-sensitive Syndrome with eosinophilia and systemic symptoms consists in rash, hematological abnormalities, lymphadenopathy and organ involvement. We report the case of a 12-year-old male patient who developed this pathology after initiating anticonvulsant therapy with carbamazepine. We consider that it is important to be aware of this disease and to include it among the differential diagnoses in patients with similar conditions because this syndrome is life-threatening.

Síndrome de hipersensibilidad a medicamentos con exantema, eosinofilia y síntomas sistémicos inducido por carbamazepina / Drug rash with eosinophilia and systemic symptoms syndrome induced by carbamazepine: Case report

RESUMEN El síndrome de hipersensibilidad a medicamentos, con exantema, eosinofilia y síntomas sistémicos (Drug Rash Eosinophylia with Systemic Symptoms, DRESS) es una reacción a diferentes medicamentos, principalmente anticonvulsivos, el cual cursa con compromiso sistémico y lesiones eritematosas, al igual que ocurre en diversas dermatosis por reacción a medicamentos. Este síndrome es una condición clínica poco frecuente, cuyo diagnóstico requiere un alto grado de sospecha por parte del personal clínico. Si no se hace un diagnóstico oportuno y se suministra el tratamiento adecuado, puede confundirse con otros tipos de alergias a medicamentos que implican riesgo de muerte. Se presenta el caso de un paciente de 22 años de edad con alteración del neurodesarrollo a quien se le inició tratamiento con carbamazepina. Dos meses después consultó debido a la aparición de síntomas generales y lesiones eritematosas en la piel, inicialmente en el tronco. En la atención ambulatoria se le prescribieron antihistamínicos y antipiréticos, con los cuales no mejoró adecuadamente; su condición empeoró, con la aparición de lesiones en la piel y síntomas sistémicos propios del síndrome DRESS. Al cabo del tratamiento farmacológico administrado durante su hospitalización según los lineamientos recomendados, las manifestaciones y complicaciones asociadas con el síndrome remitieron, la administración de esteroides pudo reducirse gradualmente y, finalmente, el paciente fue dado de alta.

ABSTRACT Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a hypersensitivity reaction associated with a variety of drugs, mainly anticonvulsants, which is characterized by systemic symptoms and erythematous lesions, common to other toxicodermas. It is an uncommon clinical entity that requires a high suspicion by clinical staff given its varied initial presentation, and the fact that symptoms can overlap with those of other adverse cutaneous reactions to drugs. Without early diagnosis and appropriate treatment, mortality increases. We report the case of a 22-year-old patient with impaired neurodevelopment who received treatment with carbamazepine. Two months later he presented with general symptoms and skin erythematous lesions that began on his trunk. The patient received outpatient care with antihistamines and antipyretics without an appropriate response. His case progressed with increased skin lesions and systemic symptoms that met the diagnostic criteria for DRESS syndrome. He was hospitalized and received medical treatment according to recommended guidelines. The patient's condition improved as his symptoms and associated complications resolved. He was discharged with gradual clearing of the steroid therapy.

Infección por virus herpes humano 6 en un paciente inmunocompetente con síndrome DRESS secundario a carbamazepina / Human herpes virus 6 infection in an inmunocompetent patient with carbamazepine-induced DRESS syndrome

El síndrome DRESS (drug reaction with eosinophilia and systemic symptoms) constituye una reacción adversa a fármacos, potencialmente mortal, caracterizada por una erupción cutánea polimorfa asociada a fiebre, linfadeno-patías y compromiso multiorgánico con eosinofilia. Presentamos el caso clínico de un hombre inmunocompetente con un síndrome DRESS secundario a carbamazepina que cursó concomitantemente con una meningoencefalitis por virus herpes humano 6 (VHH-6). El rol patogénico del VHH-6 en el síndrome DRESS sigue siendo controversial; sin embargo, dada la importancia diagnóstica y eventualmente pronóstica de la infección por VHH-6, su tamizaje sería recomendable dentro del estudio de estos pacientes.

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) is an adverse life-threatening drug reaction characterized by a polymorphous rash associated with fever, lymphadenopathy and multiorgan involvement with eosinophilia. We present the case of an immunocompetent man with DRESS syndrome secondary to carbamazepine, that developed concomitantly meningoencephalitis caused by human herpes virus 6 (HHV-6), and a review of literature. The pathogenic role of HHV-6 in DRESS syndrome remains controversial. Given the diagnostic and possibly prognostic significance of HHV-6, the screening seems to be a good measure to use in the clinical management of these patients.

HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. MATERIALS AND METHODS: We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. RESULTS: HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. CONCLUSION: HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN.

Reacción por drogas con eosinofilia y síntomas sistémicos (síndrome de DRESS): Estudio retrospectivo de nueve casos / Dress syndrome: Report of nine cases

Background: DRESS Syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is an uncommon disease caused by drugs. It is characterized by a polymorphic disseminated eruption with fever and multiple organ dysfunction. Aim: To report the etiology, characteristics, treatment, prognosis, and follow up of patients with DRESS Syndrome admitted to a clinical hospital. Material and Methods: Review of medical records of patients admitted for drug reactions, selecting those patients complying with clinical criteria for DRESS Syndrome. Drugs used during three months prior to the onset of symptoms were evaluated as possible causes of the disease. Results: Nine patients aged 16 to 68 years (six males) complied with the clinical criteria for the disease. The causative medications were carbamazepine in three patients, phenytoin in three, antituberculous drugs in two and amoxicillin in one. All were treated with systemic steroids with a complete clinical resolution. Conclusions: DRESS syndrome is usually underdiagnosed and has a good response to systemic steroids.

Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study / Carbamazepina para prevenção de náusea e vômito induzidos por quimioterapia: um estudo piloto

CONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV) still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV. DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life. RESULTS: None of the ten patients (0%) presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life. CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population. .

CONTEXTO E OBJETIVO: Náusea e vômito são inconvenientes importantes para pacientes submetidos a quimioterapia. A despeito do tratamento preventivo padrão, náuseas e vômitos induzidos por quimioterapia (NVIQ) ocorrem em aproximadamente 50% dos pacientes. Na tentativa de otimizar este tratamento, avaliamos os possíveis efeitos da carbamazepina na prevenção de náuseas e vômitos induzidos por quimioterapia. TIPO DE ESTUDO E LOCAL: Estudo fase II, prospectivo, não randomizado, aberto, realizado em um serviço público brasileiro de oncologia. MÉTODOS: Recrutaram-se continuamente pacientes alocados para o primeiro ciclo de quimioterapia altamente emetogênica. Além do protocolo anti-emético padrão disponibilizado, os pacientes receberam carbamazepina, por via oral, em doses escalonadas, a partir do terceiro dia anterior até o quinto dia após a quimioterapia. Dada a escassa evidência de eficácia dos anticonvulsivantes na prevenção de NVIQ, adotamos o desenho de Simon em duas fases, que deveria incluir 43 pacientes a não ser que prevenção completa global não fosse alcançada em 9 dos primeiros 15 participantes. O questionário "Functional Living Index-Emesis" foi usado para avaliar o impacto na qualidade da vida. RESULTADOS: Nenhum dos 10 pacientes (0%) apresentou prevenção completa global. Três tiveram a carbamazepina suspensa por sonolência e vômito antes da quimioterapia. Sete foram capazes de tomar a medicação por todo o período proposto e nenhum obteve resposta, sendo então interrompido o estudo. Não houve impacto na qualidade da vida. CONCLUSÃO: Carbamazepina não foi efetiva para prevenção de NVIQ e apresentou perfil deletério de efeitos adversos nesta população. .

Protective role of melatonin and taurine against carbamazepine-induced toxicity in freshly isolated rat hepatocytes / Rol protector de la melatonina y taurina contra la toxicidad inducida por la carbamazepina en hepatocitos de rata recién aislados

Carbamazepine is widely used in a broad spectrum of psychiatric and neurological disorders. Idiosyncratic hepatotoxicity is a well-known adverse reaction associated with carbamazepine. Hepatotoxicity is rare, but a real concern when initiating therapy. It was found that oxidative stress is a potential mechanism for carbamazepine-induced hepatotoxicity. Present study evaluated the hepato protective role of taurine and melatonin against carbamazepine-induced hepatotoxicity. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. Cells were treated with 400 uM carbamazepine, 1mM taurine, and 1mM melatonin. Cell death, reactive oxygen species formation, lipid peroxidation, and mitochondrial membrane depolarization were assessed as toxicity markers and the effects of taurine and melatonin administration on them were investigated. Our results showed that carbamazepine induced oxidative stress; increased ROS formation and lipid peroxidation products and also decreased mitochondrial membrane potential (DYm). Carbamazepine caused a decrease in cellular glutathione content and an elevation in oxidized glutathione levels. Our investigation showed that preincubation of hepatocytes with taurine (1 mM) could alleviate oxidative damages induced by carbamazepine; melatonin was also a good antioxidant to protect hepatocytes against cytotoxicity induced by carbamazepine. It may be concluded that taurine and melatonin are effective antioxidants to prevent carbamazepine-induced hepatotoxicity. Following our findings, further studies are suggested on the antioxidant effects of taurine and melatonin in patients receiving carbamazepine.

La carbamazepina es ampliamente utilizada en un gran espectro de trastornos psiquiátricos y neurológicos. La hepatotoxicidad idiosincrásica es una conocida reacción adversa asociada con la carbamazepina. La hepatotoxicidad es rara, pero es una preocupación real al iniciar el tratamiento. Se ha reportado que el estrés oxidativo es un potencial mecanismo para la hepatotoxicidad inducida por carbamazepina. El presente estudio evaluó la función hepato-protectora de la taurina y melatonina contra la hepatotoxicidad inducida por carbamazepina. Los hepatocitos se prepararon por el método de perfusión de la enzima colagenasa a través de la vena porta. Las células fueron tratadas con 400 uM de carbamazepina, 1 mM de taurina, y 1 mM de melatonina. La muerte celular, formación de especies reactivas de oxígeno (ERO), peroxidación de lípidos, y despolarización de la membrana mitocondrial fueron evaluadas como marcadores de toxicidad, junto con investigar los efectos de la taurina y melatonina administrada en ellos. Nuestros resultados mostraron estrés oxidativo inducido por carbamazepina, con aumento de las ERO, formación de productos de la peroxidación lipídica y disminución del potencial de membrana mitocondrial (DYm). La carbamazepina causó una disminución en el contenido celular de glutatión y una elevación de los niveles de glutatión no-oxidado. Se observó que la preincubación de los hepatocitos con taurina (1 mM) podría aliviar los daños oxidativos inducidos por carbamazepina; además la melatonina también fue un buen antioxidante para proteger a los hepatocitos. Se puede concluir que tanto la taurina y melatonina son antioxidantes eficaces para prevenir la hepatotoxicidad inducida por carbamazepina. Tras nuestros resultados, se sugiere estudiar los efectos antioxidantes de la taurina y melatonina en pacientes tratados con carbamazepina.

Informe levetiracetam comprimidos en monoterapia para epilepsia / Report levetiracetam monotherapy tablets for epilepsy

El mecanismo de acción de levetiracetam no es todavía totalmente conocido. Estudios in vitro, han demostrado la unión de levetiracetam con alta afinidad a la proteína 2A de la vesícula presináptica (SV2A), proteína que parece estar involucrada en la fusión de las vesículas y la exocitosis de neurotransmisores. Otros mecanismos son la inhibición de la modulación negativa del GABA asociada a Zn2+, las corrientes de Ca2+ de tipo N dependientes de voltaje y la liberación de GABA. Se definieron las siguientes preguntas PICO, con el fin de desarrollar la búsqueda bibliográfica que nos permita evaluar la eficacia y seguridad de la droga que se pretende incorporar: En pacientes con epilepsia el levetiracetam en monoterapia es más efectivo que la monoterapia con acido valproico, carbamazepina, lamotrigina, fenobarbital o fenitoína? En pacientes con epilepsia el levetiracetam en monoterapia es más seguro que la monoterapia con acido valproico, carbamazepina, lamotrigina, fenobarbital o fenitoína? En niños con epilepsia el levetiracetam en monoterapia es menos costoso que la monoterapia con acido valproico, carbamazepina, lamotrigina, fenobarbital o fenitoína? De esta forma se realizó la búsqueda bibliográfica por dos investigadores en forma independiente a través de las bases de datos Cochrane, Medline y google académico. Basados en los puntos de eficacia, seguridad y análisis de costos, dado que el levetiracetam no demostró ser más eficaz ni más seguro ni menos costoso, se recomienda su no inclusión en el formulario terapéutico hasta tanto no se cuente con evidencia sólida que demuestre lo contrario. En casos de excepción podría considerarse su uso para \r\npacientes refractarios a múltiples DAEs incluidas en el formularios terapéutico provincial.

Preliminarily analysis of carbamazepine [CBZ] C[0] in patients visited Isfahan epileptic clinics

Carbamazepine [CBZ] is mostly considered as the first line of effective treatment against simple or complex partial seizure and primary-secondary generalization. To prevent side-effects related to higher amount of CBZ minimum concentration [C[0]] in body fluid or seizure attacks associated to lower amount of CBZ-C[0], the suggested minimum therapeutic concentrations range from 4 to 12 ng/ml [according to previous publications]. The aim of this preliminarily study was to investigate the scope of discrepancy associated to the C[0] of CBZ in patients visited Isfahan Epileptic Clinic. A cross-sectional study of 22 patients located in neurology ward of Isfahan Neurosciences Research Centre [INRC] was carried out between April 1, 2012 and December 31, 2012. Female [n = 9] and male subjects [n = 13] with a mean age of 27.4 years [range; 16-38 years] were studied. Pharmacological [CBZ-C[0]] and demographical variables were recorded and processed in excel. The results of CBZ-C[0] showed wide inter-individual variability. The mean value of CBZ-C[0] was 7.2 ng/ml. In 10 out of 22 patients, CBZ-C[0] were lower than the suggested therapeutic window [4-12 ng/ml]. CBZ-C[0] in nine patients was non-detectable and in one patient was 0.5 ng/ml [45% <4 ng/ml]. In 55% of the patients, CBZ-C[0] ranged from 4.8 to 12 ng/ml. A schedule therapeutic drug monitoring based on measurement of CBZ-C[0] for individual patient could be a practical marker to achieve therapeutic objectives. Further study related to correlating of CBZC[0] to clinical events in Iranian Epileptic population seems to be valuable

Uso y abuso en la prescripción de la carbamazepina en el Área Sur de Morón / Use and abuse in carbamazepine prescription in the South Area of Morón

Se realizó un estudio cuantitativo, retrospectivo y descriptivo para determinar el uso y abuso de la prescripción de carbamazepina en el Área Sur de Morón, se distribuyeron los pacientes según sexo, edad, criterio de prescripción, precisar dosis indicada, determinar el tiempo de duración de la terapia, describir las interacciones medicamentosas y narrar las reacciones medicamentosas encontradas. Se determinó que el sexo más afectado fue el masculino con un 50,87 por ciento, el grupo de edad más afectado fue el de 25 a 59 con un 54, 31 por ciento, el criterio que prevaleció fue la epilepsia con un total de 70 pacientes y un 60,74 por ciento, la dosis que con mayor frecuencia se usó fue la de 3 tabletas diarias, el tiempo de duración de la terapia por un año fue el más recomendado con un total de 106 pacientes para un 91,38 por ciento, la interacción medicamentosa más frecuente fue con el fenobarbital en un 70,69 por ciento y la reacción medicamentosa más común fue el vértigo para un 14,65 por ciento.

Efficacy, Safety and Tolerability of Trioptal®d: (Oxcarbazepine) in Children and Adolescents with Newly Diagnosed Partial Seizures or Generalized Tonic-Clonic Seizures: Results of a 6 Months, Prospective, Open-Label, Multicentre, Non-Comparative, Observational Post-Marketing Surveillance Study.

Objective: The current study was designed to analyze the extended efficacy and safety of Trioptal® (Oxcarbazepine) in treatment of children and adolescents with newly diagnosed partial seizures or generalized tonicclonic seizures in Indian population. Methods: This was an open-label non-randomized multi-centric observational prospective study (PMS study) across 54 centers in India. Treatment with Trioptal® (Oxcarbazepine) was initiated with a clinically effective dose (8-10 mg/kg/day in children) given in two divided doses as per the prescribing information. The dose was increased depending on the clinical response of the patient. In children, if clinically indicated, the dose was increased by a maximum of 10 mg/kg/day increments at approximately weekly intervals from the starting dose, to a maximum daily dose of 60 mg/kg/day. The efficacy of Trioptal® was assessed primarily by the percentage of seizure-free patients at 24 weeks. Secondary efficacy of the treatment was assessed through: reduction in seizure frequency at 24 weeks and the Global assessment of efficacy by the investigator at 24 weeks. Results: A total of 485 subjects were enrolled in the study. Majority of the subjects (52%) were stabilized at 8-15 mg/kg/day dose of Trioptal® and mean effective dose was 16.1 mg/kg/day (± 7.02). Approximately 70 % of the subjects were seizures free after 24 weeks of Trioptal® treatment and around 88% of the subjects reported the reduction in seizure of more than 50 %. The mean reduction in seizure frequency after 24 weeks of treatment was 82.3%. The overall efficacy with the Trioptal® treatment for 24 weeks was ‘good’ to ‘excellent’ in more than 97% of the subjects as per the assessment by the physician. A total of 59 adverse events were observed in 43 (8.9%) subjects. Headache was the most common adverse event being recorded in 8 subjects, followed by somnolence, nausea, vomiting, skin rash and weight gain. The overall tolerability of Trioptal® as per assessment by the patients was ‘good’ to ‘excellent’ in more than 98% of the subjects. Conclusion: Trioptal® (Oxcarbazepine) treatment is effective, safe and well tolerable in children and adolescents with newly diagnosed partial seizures or generalized tonic-clonic seizures.

Síndrome DRESS por ingestión de carbamazepina: reporte de un caso pediátrico / The DRESS syndrome by carbamazepine ingestion: report of a pediatric case

Se presentó el caso de una niña de 10 años de edad con antecedentes de ingestión de carbamazepina por diagnóstico presuntivo de epilepsia, quien ingresó en el Hospital Provincial Pediátrico Docente Eliseo Noel Caamaño, en Matanzas, en mayo del 2010, por cuadro de fiebre, rash cutáneo y vómitos al inicio, con evolución severa y la aparición de ictericia, hepato-esplenomegalia. Se realizó diagnóstico de síndrome DRESS, con evolución satisfactoria sin el uso de la terapia esteroidea. Se revisó la literatura sobre síndrome de hipersensibilidad por anticonvulsivantes, medicamentos de uso cada vez más frecuente.

We presented the case of a 10-years-old girl with antecedents of carbamazepine ingestion for epilepsy presumptive diagnosis, who entered the Teaching Pediatric Provincial Hospital Eliseo Noel Caamaño, in Matanzas, in May 2010, with fever, skin rash and vomiting at the beginning, followed by severe evolution, with jaundice and hepato-splenomegaly. We diagnosed the DRESS syndrome, with satisfactory evolution without using the steroidal therapy. We reviewed the literature about the hypersensibility syndrome for anticonvulsants, drugs of more and more frequent use.

Reação liquenoide à carbamazepina em mucosa bucal: relato de caso / Lichenoid reaction to carbamazepine in the oral mucosa: case report

As reações liquenoides por drogas são mais comuns na pele, mas também podem ocorrer na mucosa bucal. Estas lesões são de difícil diagnóstico por causa de sua semelhança clínica com às do líquen plano oral idiopático. O presente artigo relata um caso de reação liquenoide em mucosa bucal, associado ao uso de carbamazepina, no qual o processo de diagnóstico é enfatizado.

Lichenoid drug reactions are more commom in skin, but they may also occur in the oral mucosa. It is difficult to diagnose these lesions due to their clinical similarity to the idiopathic oral lichen planus lesions. The present article reports a case of lichenoid reaction in oral mucosa associated to the use of carbamazepine, emphasizing the diagnostic process.

Reacciones cutáneas adversas a anticonvulsivantes y estabilizadores del ánimo / Adverse cutaneous reactions to anticonvulsants and mood stabilizers

Anticonvulsivantes y estabilizadores del ánimo principalmente el ácido valproico, lamotrigina y carbamazepina, poseen una alta incidencia de reacciones adversas a medicamentos (RAM) severas, como eritema multiforme, Síndrome Stevens- Johnson y necrolisis epidérmica tóxica, asociadas. Existen signos de alarma para su sospecha diagnóstica precoz, que permiten indicar la temprana suspensión del fármaco sospechoso e iniciar la terapia de soporte únicas medidas que han demostrado una clara disminución en la mortalidad. La inmunoglobulina G intravenosa se recomienda por su seguridad, sin embargo, su rol en disminuir la mortalidad es contradictorio. Los corticoides no han demostrado cambios en la mortalidad comparados con la terapia de soporte exclusiva. Se ha intentado mantener el tratamiento con lamotrigina, por sus cualidades terapéuticas, pese a la aparición de RAM cutáneas. De hecho, en estudios recientes en pacientes que han desarrollado RAM leves a este producto se ha demostrado un éxito de reexposición de 85 por ciento-87 por ciento mediante una lenta titulación de la dosis.

Anticonvulsants and mood stabilizers mainly valproic acid, lamotrigine and carbamazepine are medications that have a high incidence of severe adverse drug reactions (ADRs), such erythema multiforme, Stevens- Johnson syndrome and toxic epidermal necrolysis. Early diagnosis based in systemic and cutaneous alarm signs have been described, allowing premature discontinuation of suspected drugs and start supportive therapy; these are the only measures that have that have shown clear reduction in mortality. The use of intravenous immunoglobulin G is recommended for their safety, but studies regarding their role in reducing mortality are conflicting. Corticosteroids have not proved changes in mortality compared with exclusive supportive care. Due to therapeutic quality Lamotrigine is used despite the incidence of ADRs. In fact in recent studies patients with mild ADRs to this drug have shown between 85 percent-87 percent of success, when patients are re-exposed through a slow increasing in dosage.

Possible teratogenic effects of antiepileptics in albino rats: comparative study between old and new generations: part I

All of the antiepileptic drugs [AEDs] are either known or suspected of being teratogenic. The possible mechanism of teratogenicity is likely to be multiple for the same drug. This is of major concern for all women with epilepsy using these drugs are delicately balanced between seizure control and the adverse effects the AEDs. The use of conventional AEDs eg. Carbamazepine control more than two thirds of the epileptic patients. In recent years, the number of commercially available AEDs has steadily increased eg. lamotrgine and levetiracetam.160 pregnant female albino rats were used in this study. Animals were classified randomly into eight groups; each group contained 20 pregnant female rats. Negative control group received nothing and positive control group received normal saline. Treated groups: each group received either the therapeutic dose or 1/4 LD50 of carbamazepine, lamotrigine or levetriacetam. The drugs were given by gastric tube from 6[th] day up to the 19[th] day of gestation. Teratological evaluation:the fetuses [both living and dead] in each group were weighted their crown rump length measured and morphological examination included: Head size and shape, orofacial development, vertebral column tail and abdomen, umbilicus and external genitalia Maternal findings showed high death rate in 1/4 LD50 of lamotrigine treated group; weight gain was dose dependant with highest effect in the lamotrigine treated groups. The fetal findings showed highest embrolethality and least litter siza in lamotrigine treated groups; while the fetal growth determined by weight gain and crown rumplength was retarded more in carbamazepine and lamotrigine treated groups than in levetiracetam treated groups. The morphological findings revealed that the highest percentage of congenital anomalies were in the dose of 1/4 LD50 of lamotrigine followed by carbamazepine and levetiracetam. The AEDs are potentially teratogenic and in utero exposure can increase the risk of adverse outcomes in off springs born epileptic mothers. The new AED lamotrigine caused gross fetal retardation even in therapeutic dose. Levetiracetam caused growth retardation in the therapeutic dose more than carbamazepine in the corresponding dose although it had the best effect on maternalparameters. As regard the congenital anomalies lamotrigine was the safest durg in the therapeutic dose