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.

[Invitro comparison studying of dissolution profiles for pharmacopoeial and nonpharmacopoeial native anticonvulsants oral solid dosage forms with brand name]

Dissolution is very important parameter in releasing of active pharmaceutical ingredient from dosage form, and this directly correlate with absorption process and consequently with bioavailability of oral dosage forms [tablet]. Oxcarbazepine is an oral anticonvulsant, and in this research we work on Invitro comparison of dissolution protiles for two native oxcarbazepine tablet 300 mg products with the same of patented [trileptal[rigstered]], calculating similarity factor f[2] as the base of comparison, the value of similarity factors were for product-A [f[2]=77.1], for product-B [f[2]=51] appear similarity of dissolution profiles of two previous product with the same of patented

Papel de la monoterapia con nuevos fármacos antiepilépticos en el tratamiento de la epilepsia infantil / Role of monotherapy with new antiepileptic drugs in the treatment of childhood epilepsy

En este trabajo se revisa la información actual sobre el uso de los nuevos fármacos antiepilépticos (FAEs) en monoterapia en niños, resaltando nuestra experiencia personal. Específicamente, se incluyen los siguientes FAEs: lamotrigina (Lamictal®), topiramato (Topamax®), zonisamida (Zonegran®), levetiracetam (Keppra®), y oxcarbacepina (Trileptal®). Todos estos FAEs tienen un amplio espectro de acción en el tratamiento de crisis epilépticas parciales y generalizadas, excepto la oxcarbacepina, que es eficaz exclusivamente en crisis parciales. No está claro si la monoterapia con estos FAEs, en comparación con los FAEs clásicos (fenobarbital, fenitoína, carbamacepina, valproato sódico), proporciona una mayor eficacia y/o causa menos efectos secundarios y, si por lo tanto, mejora significativamente la calidad de vida de los niños con epilepsia. Se necesitan más estudios para poder contestar estas preguntas.

In this paper we review the current information regarding the use of new antiepileptic drugs (AEDs) used as monotherapy in children. We specifically include the following AEDs: lamotrigine (Lamictal®), topiramate (Topamax®), zonisamide (Zonegran®), levetiracetam (Keppra®), and oxcarbazepine (Trileptal®). All of these AEDs have a broad spectrum of action in the treatment of partial and generalized seizures, except Oxcarbazepine, which is effective only in partial seizures. It is unclear whether or not monotherapy with the new AEDs offers higher efficacy and/or lower side effects compared to classic AEDs (phenobarbital, phenytoin, carbamazepine, or valproate) thereby significantly improving the quality of life in children with epilepsy. More studies are needed to answer these questions.

Oxcarbazepine for refractory epilepsy: systematic review of the literature / Oxcarbazepina para epilepsia refratária: revisão sistemática da literatura

CONTEXT AND OBJECTIVE: It has been estimated that 50 million people worldwide suffer from epilepsy and around 30 percent will not achieve adequate control over the disease. The aim was to evaluate the effectiveness of oxcarbazepine for refractory partial or generalized epilepsy. METHODS: Systematic review. A search was conducted in the PubMed, Lilacs, EMBASE and CENTRAL databases. Studies were analyzed using the Cochrane Collaboration methodology. RESULTS: Four randomized clinical trials of medium to poor methodological quality were included. Among the adult patients, the chances that they would obtain a 50 percent reduction in seizure frequency were greater after using oxcarbazepine at doses of 600 mg (relative risk, RR 2.11; 95 percent confidence interval, CI 1.32 to 3.35), 1,200 mg (RR 3.24; 95 percent CI 2.11 to 4.98) and 2,400 mg (RR 3.83; 95 percent CI 2.59 to 5.97). Among the children, the response in the group using oxcarbazepine was also greater (RR 2.11; 95 percent CI 1.32 to 3.35). The oxcarbazepine doses of 1,200 mg (RR 17.59; 95 percent CI 2.37 to 130.35) and 2,400 mg (RR 25.41; 95 percent CI 6.26 to 103.10) were effective for keeping patients probably free from seizures, but the dose of 600 mg was not. There was no significant difference between oxcarbazepine and carbamazepine for controlling the crises. CONCLUSIONS: There is moderate evidence indicating that oxcarbazepine is effective as an alternative treatment for partial or generalized epilepsy in children and adults who were refractory to previous treatment

CONTEXTO E OBJETIVO: Estima-se que 50 milhões de pessoas no mundo sofrem de epilepsia e cerca de 30 por cento não obterão controle adequado da doença. O objetivo foi de avaliar a efetividade de oxcarbazepina na epilepsia parcial ou generalizada refratária. MÉTODOS: Revisão sistemática. A busca foi nas bases de dados PubMed, Lilacs, EMBASE e CENTRAL. Os estudos foram analisados segundo a metodologia da Cochrane Colaboration. RESULTADOS: Foram incluídos quatro ensaios clínicos aleatórios de média a má qualidade. Entre os pacientes adultos as chances de obterem redução de 50 por cento na frequência de convulsões foram maiores após uso de oxcarbazepina na dose de 600 mg (risco relativo, RR 2.11; intervalo de confiança, IC 95 por cento 1,32 a 3,35; na dose de 1.200 mg (RR 3,24; IC 95 por cento 2,11 a 4,98) e na dose de 2.400 mg (RR 3,83; IC 95 por cento 2,59 a 5,97). Entre as crianças a resposta no grupo usando oxcarbazepina também foi significativamente maior (RR 2,11; IC 95 por cento 1,32 a 3,35). Oxcarbazepina mostrou probabilidade dos pacientes ficarem livre de convulsões, ser eficaz nas doses de 1.200 mg (RR 17,59; IC 95 por cento 2.37 a 130,35) e 2.400 mg (RR 25,41; IC 95 por cento 6,26 a 103,10) não foi eficaz na dose de 600 mg. Não houve diferença estatística significante entre oxcarbazepina e carbamazepina no controle das crises. CONCLUSÕES: Há evidências moderada de que a oxcarbazepina é um tratamento eficaz como alternativa para os casos de epilepsia parcial ou generalizada em crianças e adultos que tenham sido refratários a tratamento prévio.

A reverse phase high performance liquid chromatography method for simultaneous estimation of melatonin, carbamazepine epoxide and carbamazepine simultaneously in serum.

Monitoring of plasma antiepileptic drugs is useful for better clinical management in epileptic patients, particularly in children. Carbamazepine (CBZ) is one of the commonly prescribed anticonvulsants. The active metabolite of carbamazepine-carbamazepine-10-11 epoxide (CBZ-Epo) also exhibits anticonvulsant effect. The pineal hormone, melatonin exerts an anticonvulsant effect in experimental seizure models and recently has also been used in cases of childhood epilepsy. To facilitate the simultaneous plasma estimation of carbamazepine, carbamazepine epoxide, and melatonin, a new HPLC method was developed. Waters millennium 2010 chromatography manager with a 515 HPLC pump and Waters 24879 dual absorbance UV detector was used. A 25 microlitre of sample and standards were injected, and chromatographic separation was achieved by Merck C18 reverse phase column particle size 5 micro, 250 mm x 4 mm. It was quantitated at UV light 210 nm. The retention times of melatonin, CBZ-Epo, and CBZ were 6.3 min, 7.5 min, and 13.9 min respectively. The Mobile Phase used was water: acetonitrile (70:30), pH 3.0 adjusted with orthophosphoric acid at the flow rate of 1 ml/min. The limits of detection of melatonin, carbamazepine epoxide, and carbamazepine were 800, 500, and 1300 pg respectively.

clinical overview of the new antiepileptic drugs

Over the past decade, several new antiepileptic drugs [AEDs] have become available including Gabapentin, Lamotrigine, Topiramate, Tiagabine, Oxcarbazepine, Levetiracetam, Zonisamide, Vigabatrin and Felbamate. These drugs had proved their efficacy in various types of seizures. Lamotrigine and Topiramate were suggeseted as effective for use as monotherapy for generalized seizures, and Topiramate, Lamotrigine, Oxcarbazepine and Gabapentin for partial onset seizures, and Vigabatrin for infantile spasms. All the new anti-epileptic drugs are also effective as add-on therapy for partial seizures without or with secondary generalization. This article briefly reviews the pharmacodynamics of the new antiepileptic drugs to provide information that physicians in the Kingdom particularly non-epileptologists for rational choice and judicious use of these agents

Padrão eletrográfico ictal subclínico em um caso de epilepsia parcial benigna da infância com pontas centro-temporais / Ictal electroencephalographic subclinical pattern in a case of benign partial epilepsy with centrotemporal spikes

Há poucos relatos na literatura do padrão ictal na epilepsia parcial benigna da Infância com pontas Centrotemporais (EPCT). Esse trabalho descreve o caso de um menino, de 7 anos, sem antecedentes de sofrimento neonatal ou distúrbio do desenvolvimento neuropsicomotor, com de história familiar de epilepsia. A ressonância magnética do encéfalo foi normal. O paciente apresentou uma única crise durante sono, seguida de breve déficit motor membro superior esquerdo. O EEG dois dias após a crise evidenciou atividade de base normal com pontas centro-temporais bilaterais, e duas descargas subclínicas de ponta-onda rítmicas, de duração superior a 50 segundos em região centro-temporal direita. Este padrão de descarga rítmica não foi descrito na EPCT anteriormente.

Oxcarbazepina: un nuevo anticonvulsivante / Oxcarbazepine: a new anticonvulsant

The new anticonvulsivant oxcarbamazepine (OXC) is a keto analogue of carbamazepine. Both share a similar therapeutic profile, that includes mainly the treatment of partial epilepsies but probably neuralgias and affective disorders as well. Most OXC dose dependent adverse effects are similar to carbamazepine's, including ataxia, nystagmus, diplopia; other side effects are probably less common than those induced by carbamazepine, with the exception of hyponatremia, that occurs more often with OXC, although mainly asymptomatic. One of the main advantages of this new drug is its lack of enzyme induction potential, making easier to use it in combination with other drugs when necessary; accordingly, several clinical studies have shown absence of interaction between OXC and other medications