Oxcarbazepina en el tratamiento de la epilepsia focal refractaria
ABSTRACT Introducción: Los objetivos del estudio son analizar la eficacia y la tolerabilidad de la oxcarbazepina en pacientes afectos de epilepsia focal refractaria. Material y métodos: Estudio prospectivo con treinta pacientes tratados con oxcarbazepina a dosis de 1.200-1.800 mg. Visita basal y visitas a los dos, cuatro y seis meses. Resultados: Se registraron cuatro abandonos por ineficacia y ninguno por efectos adversos. La tasa media de reducción fue del 32% y la tasa de respondedores (reducción =50%) del 26,7 %. Cinco pacientes quedaron libres de crisis. La respuesta fue superior en los pacientes que no padecen crisis parciales con generalización secundaria. Discusión: La oxcarbazepina es un fármaco útil en el tratamiento de la epilepsia focal sintomática refractaria a otros tratamientos.
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ABSTRACT: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjunctive therapy for uncontrolled partial seizures and to determine the relationship between trough plasma 10-monohydroxy derivative concentrations and OXC safety and efficacy. This multinational, multicenter, randomized, 28-week, double-blind, placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures. The primary efficacy variable was percentage change in seizure frequency per 28 days relative to baseline. The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively (all p < or = 0.0001). Of patients in the 600, 1200, or 2400 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduction in seizure frequency compared with 13% for placebo (all p < 0.001). Higher plasma 10-monohydroxy derivative concentrations were associated with larger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse events. The most common adverse events were related to the nervous and digestive systems. OXC is safe and effective as adjunctive therapy in patients with uncontrolled partial seizures. OXC 600 mg/d was the minimum effective dosage; effectiveness of OXC increased with dose. The rapid and fixed titration to high doses was associated with an increased risk of adverse events, which could potentially be reduced by adjusting concomitant antiepileptic medication and by using a slower, flexible OXC titration schedule.Epilepsia 12/2000; 41(12):1597-607. DOI:10.1111/j.1499-1654.2000.001597.x · 4.58 Impact Factor
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ABSTRACT: To evaluate the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC) in medically refractory partial epilepsy. This study is the open-label extension phase that followed a multicenter, randomized, double-blind, dose-response clinical study of OXC monotherapy in patients with medically refractory partial epilepsy. We analyzed the efficacy, tolerability, and safety of OXC during the first 48 weeks of open-label therapy. To evaluate efficacy, we compared the change in seizure frequency throughout the 48 weeks of treatment with OXC with the baseline seizure frequency that preceded the double-blind phase of the core study by an intent-to-treat and completer analysis. Safety and tolerability were evaluated by using an intent-to-treat analysis. Of the 87 patients enrolled in the double-blind study, 76 patients participated in the open-label extension phase. Fifty-five (72%) patients completed 48 weeks of open-label treatment on a median OXC dose of 2,400 mg/day. Based on an intent-to-treat analysis, the median reduction in seizure frequency was 47%(p = 0.0054); the 50 and 75% responder rates were 46.1 and 25.0%, respectively, with 6.6% of patients remaining seizure free. The completer analysis yielded comparable efficacy results. OXC was well tolerated, with 13% of patients exiting because of adverse events. The six most common adverse events, irrespective of their causal relation to OXC, were dizziness, headache, fatigue, diplopia, nausea, and rash. For the most part, these adverse events tended to be transient. The efficacy of OXC is sustained with good safety and tolerability profiles during long-term treatment of patients with medically refractory partial epilepsy.Epilepsia 10/2003; 44(9):1160-5. DOI:10.1046/j.1528-1157.2003.54102.x · 4.58 Impact Factor
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ABSTRACT: Oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) is a 10-keto analogue of carbamazepine with anticonvulsant activity. In newly diagnosed adult patients, oxcarbazepine monotherapy is as effective as phenytoin and vaiproic acid at reducing generalised tonic-clonic and partial seizure frequency. Furthermore, oxcarbazepine 2400 mg/day as monotherapy has also proved effective in the treatment of refractory partial seizures in adult patients. Oxcarbazepine 600, 1200 and 2400 mg/day as adjunctive therapy significantly reduced seizure frequency compared with placebo in 692 patients with refractory partial seizures. The efficacy of oxcarbazepine monotherapy is similar to that of phenytoin in the treatment of children and adolescents with newly diagnosed partial or generalised tonic-clonic seizures. Additionally, adjunctive therapy with oxcarbazepine was significantly more effective than placebo at reducing seizure frequency in children and adolescents with refractory partial seizures. The most commonly reported adverse events associated with oxcarbazepine monotherapy and/or adjunctive therapy in adults and/or children are somnolence, dizziness, headache, nausea and vomiting. Oxcarbazepine monotherapy is better tolerated than phenytoin (in both adults and children) and valproic acid (in adults), and although 75 to 90% of adult patients in 5 recent monotherapy studies reported adverse events while receiving oxcarbazepine, <8% withdrew from treatment because of them. Acute hyponatraemia, although usually asymptomatic, develops in 2.7% of patients treated with oxcarbazepine. Adverse events most likely to resolve upon switching to oxcarbazepine therapy from treatment with carbamazepine are undetermined skin reactions (rashes, pruritus, eczema), allergic reactions and a combination of malaise, dizziness and headache. Although oxcarbazepine does have a clinically significant interaction with some drugs (e.g. phenytoin and oral contraceptives), it has a lower propensity for interactions than older antiepileptic drugs (AEDs) because its major metabolic pathway is mediated by noninducible enzymes. CONCLUSION: Oxcarbazepine as monotherapy is a viable alternative to established AEDs in the treatment of partial and generalised tonic-clonic seizures in adults and children. Furthermore, it is also effective as adjunctive therapy in the treatment of refractory partial seizures in both age groups. In addition, the drug is tolerated better than the older, established AEDs, and has a lower potential for drug interactions. These attributes make oxcarbazepine an effective component in the initial treatment of newly diagnosed partial and generalised tonic-clonic seizures, and also as an adjunct for medically intractable partial seizures in both adults and children.CNS Drugs 02/2001; 15(2):137-63. DOI:10.2165/00023210-200115020-00005 · 4.38 Impact Factor