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Oxcarbazepine

Epilepsia 2001 Jun;42(6):793-5
Oxcarbazepine in focal epilepsy and hepatic porphyria: a case report.
Gaida-Hommernick B, Rieck K, Runge U
Department of Neurology, Ernst-Moritz-Arndt-University, Ellernholzstrasse 1-2, 17487 Greifswald, Germany.

PURPOSE: Despite the development of new antiepileptic agents (AEDs), the therapy of epilepsies along with hepatic porphyrias remains difficult. Most AEDs such as carbamazepine (CBZ), phenytoin (PHT), valproate (VPA), and lamotrigine (LTG) may precipitate clinically latent porphyria by inducing hepatic metabolism and increasing hepatic heme synthesis. Actually, only gabapentin (GBP), an AED without any hepatic metabolism, is known as a potential therapy for partial seizures in patients having hepatic forms of porphyria. METHODS: We present the case of a 28-year-old man with porphyria cutanea tarda (PCT) who has had pharmacoresistant epilepsy with complex partial and secondarily generalized seizures since early childhood. Despite having undergone several AED therapies over the years, no seizure-free interval had been observed. Only CBZ could cause a seizure reduction, but this treatment had to be discontinued as an elevation of the transaminases as well as pruritus and erythema were noted. The patient was then started on oxcarbazepine (OCBZ), a ketoanalogue of CBZ similar in its pharmacologic mechanism as well as its clinical use, but which, in contrast to CBZ, has only a low hepatic induction of microsomal enzymes. A final maintenance dose four times higher than that of CBZ was prescribed. RESULTS: In the follow-up, the patient stopped having seizures, and his liver functions became normal. CONCLUSIONS: It can be concluded that OCBZ can successfully be administered to patients with hepatic porphyria and focal epilepsy who did not respond to treatment with GBP.

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Neurology 2001 Sep 11;57(5):864-71
Oxcarbazepine (Trileptal) as monotherapy in patients with partial seizures.
Sachdeo R, Beydoun A, Schachter S, Vazquez B, Schaul N, Mesenbrink P, Kramer L, D'Souza J
New Jersey Comprehensive Epilepsy Center, University of Medicine & Dentistry of New Jersey, New Brunswick, USA. sachderc@umdnj.edu

OBJECTIVE: To evaluate the efficacy and safety of oxcarbazepine (OXC) as monotherapy for patients with uncontrolled partial seizures. METHODS: A multicenter, double-blind, randomized, parallel-group, dose-controlled monotherapy trial compared OXC at 2400 mg/day with OXC at 300 mg/day in patients with uncontrolled partial-onset seizures previously receiving carbamazepine (CBZ) monotherapy. During a 28-day open-label conversion phase, patients were tapered off CBZ and titrated to OXC 2400 mg/day. After a 56-day open-label baseline phase on OXC 2400 mg/day, patients entered a 126-day double-blind treatment phase in which they were randomized to continue OXC at 2400 mg/day or were down titrated over 6 weeks to OXC at 300 mg/day. Patients met the efficacy endpoint by completing the double-blind treatment phase or by meeting one of four predefined exit criteria. The primary efficacy variable was time to meeting one of the exit criteria. The secondary efficacy variable was the percentage of patients meeting one of the exit criteria in each of the two treatment groups. RESULTS: Of the 143 patients enrolled, 96 were randomized in the double-blind treatment phase. Time to meeting an exit criterion was significantly in favor of the OXC 2400 mg/day group (p = 0.0001). The median time to meeting an exit criterion was 68 days for the OXC 2400 mg/day Group and 28 days for the OXC 300 mg/day Group. In addition, the percentage of patients meeting one of the exit criteria was significantly lower for the OXC 2400 mg/day Group (p = 0.0001). Overall, OXC was well tolerated with the most common adverse events consisting of fatigue, nausea, ataxia, and headache. CONCLUSION: This trial demonstrated that OXC at 2400 mg/day is well tolerated and efficacious when administered as monotherapy in patients with uncontrolled partial onset seizures.

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Acta Neurol Scand 2001 Sep;104(3):167-70
Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view.
Schmidt D, Arroyo S, Baulac M, Dam M, Dulac O, Friis ML, Kalviainen R, Kramer G, van Parys J, Pedersen B, Sachdeo R
Epilepsy Reseach Group, Goethestr.5, Berlin.

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or - in rare cases - has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.

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CNS Drugs 2001;15(2):137-63
Oxcarbazepine: an update of its efficacy in the management of epilepsy.
Wellington K, Goa KL
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz

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.

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Epilepsia 2001 Jun;42(6):741-5
The regulation of serum sodium after replacing carbamazepine with oxcarbazepine.
Isojarvi JI, Huuskonen UE, Pakarinen AJ, Vuolteenaho O, Myllyla VV
Department of Neurology, University of Oulu, FIN-90220 Oulu, Finland.

PURPOSE: To evaluate changes in serum electrolyte balance and underlying regulatory mechanisms in 10 male patients with epilepsy 2 and 6 months after replacing long-term carbamazepine (CBZ) monotherapy with oxcarbazepine (OCBZ) monotherapy. Arginine vasopressin (AVP) is thought to be most important underlying mechanism of CBZ-related hyponatremia via direct or kidney tubular mechanisms. Furthermore, AVP is as well hormonally regulated by the renin-angiotensin-aldosterone system and atrial natriuretic peptide (ANP). METHODS: The medication of the patients was changed from CBZ to OCBZ. Serum electrolytes, creatinine, albumin, aldosterone, and the N-terminal fragment of ANP (NT-proANP) concentrations were measured before and 2 and 6 months after the change in the medication. RESULTS: The mean serum sodium level diminished after the medication was changed. Serum sodium levels decreased below the reference range in two (20%) patients during OCBZ medication. Serum sodium levels decreased altogether in four patients, and remained unaltered in six patients. Serum aldosterone levels increased in the six patients whose serum sodium concentrations did not decrease, but no increase was found in the patients with decreased sodium levels during OCBZ medication. Serum NT-proANP levels decreased in all patients. CONCLUSIONS: Serum sodium levels decrease after replacing CBZ with OCBZ. The low serum NT-proANP concentrations appear to reflect the decreased serum sodium levels, but a compensatory aldosterone response may prevent the development of hyponatremia in some patients during OCBZ medication.

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Seizure 2001 Mar;10(2):87-91
Clinical recommendations for oxcarbazepine.
Smith PE
The Epilespsy unit, University Hospital of Wales, Department of Neurology, Health Park, Cardiff, Wales, UK. smithpe@cardiff.ac.uk

Oxcarbazepine (OXC) is indicated for treating partial-onset with or without secondary generalized tonic-clonic seizures, in both adults and children aged over 6 years, as monotherapy or adjuvant therapy. Trials data and extensive clinical experience demonstrate generally good tolerability and antiepileptic efficacy similar to carbamazepine (CBZ), sodium valproate or phenytoin. Since the UK launch of OXC in March 2000, UK collaborators have pooled experience to optimize prescribing recommendations for adults. Many patients are successfully managed using the prescribing information recommended titration schedule. However, evolving clinical experience suggests a slower introduction is preferable (e.g. 150 mg day one, then 300 mg daily, increased by 300 mg weekly) both for monotherapy and adjuvant therapy. Overnight 'switch' from CBZ to OXC (using CBZ:OXC ratio of 1:1.5) has been used for patients responsive to CBZ, but with dose-related side-effects. Owing to individual variations in CBZ enzyme autoinduction, however, overnight switching is advised only for those on CBZ < 800 mg daily; otherwise, slower switching is recommended. OXC is not the first choice alternative for patients developing a CBZ rash owing to increased OXC rash rate in CBZ sensitive subjects. Hyponatraemia may be more common (albeit often asymptomatic) than trials data suggest, especially in the elderly. Serum sodium monitoring is unnecessary, however, unless relevant risk factors or pointers exist. Severe haematological dyscrasias have not been reported with OXC. The enzyme inducing interaction of OXC with ethinyloestradiol and levonorgestrel necessitates additional precautions for women using hormonal contraception.

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Clin Ther 2001 May;23(5):680-700; discussion 645
Oxcarbazepine, an antiepileptic agent.
Kalis MM, Huff NA
School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences, Boston 02115, USA.

BACKGROUND: Epilepsy is a common neurologic condition. Many of the currently approved pharmacologic agents for its treatment are associated with numerous adverse drug reactions and drug interactions. OBJECTIVE: This review describes the pharmacology and therapeutic use of oxcarbazepine, an analogue of the well-known antiepileptic agent carbamazepine. METHODS: Articles for review were identified through a search of MEDLINE, International Pharmaceutical Abstracts, and EMBASE for the years 1980 through 2000. The terms used individually and in combination were oxcarbazepine, carbamazepine, epilepsy, and seizures. RESULTS: Oxcarbazepine and its primary metabolite have been effective in animal models of epilepsy that generally predict efficacy in generalized tonic-clonic seizures and partial seizures in humans. The exact mechanism of action of oxcarbazepine is unknown, although as with carbamazepine, it is believed to involve blockade of voltage-gated sodium channels. The pharmacokinetic profile of oxcarbazepine is less complicated than that of carbamazepine, with less metabolism by the cytochrome P450 system, no production of an epoxide metabolite, and lower plasma protein binding. The clinical efficacy and tolerability of oxcarbazepine have been demonstrated in trials in adults, children, and the elderly. In a double-blind, randomized, crossover trial in adults, oxcarbazepine 300 mg was associated with a decrease in the mean frequency of tonic seizures (21.4 vs 30.5 seizures during steady-state periods) and tonic-clonic seizures (8.2 vs 10.4) compared with carbamazepine 200 mg (P = 0.05). A multinational, multicenter, double-blind, placebo-controlled, randomized, 28-week trial assessed the efficacy and tolerability of oxcarbazepine at doses of 600, 1200, and 2400 mg as adjunctive therapy in patients with uncontrolled partial seizures. All 3 oxcarbazepine groups demonstrated a reduction in seizure frequency per 28-day period compared with placebo (600 mg, 26% reduction; 1200 mg, 40% reduction; 2400 mg, 50% reduction; placebo, 7.6% reduction; all, P < 0.001). A trial in children assessed the efficacy and toxicity of oxcarbazepine (median dose, 31.4 mg/kg/d) as adjunctive therapy for partial seizures. Patients receiving oxcarbazepine experienced a 35% reduction in seizure frequency, compared with a 9% reduction in the placebo group (P < 0.001). The most common adverse effects associated with oxcarbazepine are related to the central nervous system (eg, dizziness, headache, diplopia, and ataxia) and the gastrointestinal system (eg, nausea and vomiting). Compared with carbamazepine, there is an increased risk of hyponatremia with oxcarbazepine. The frequency and severity of drug interactions are less with oxcarbazepine than with carbamazepine or other antiepileptic agents. CONCLUSIONS: Oxcarbazepine may be considered an appropriate alternative to carbamazepine for the treatment of partial seizures in patients who are unable to tolerate carbamazepine. Its use in nonseizure disorders remains to be examined in large-scale clinical trials, and pharmacoeconomic comparisons of oxcarbazepine with other antiepileptic agents, particularly carbamazepine, are needed.

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Medicina (B Aires) 2000;60(6):914-8
[Pharmacokinetic variability of oxcarbazepine in epileptic patients].
[Article in Spanish]
Viola MS, Bercellini MA, Saidon P, Rubio MC
Catedra de Farmacologia, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Junin 956, 1113 Buenos Aires, Argentina. msviola@huemul.ffyb.uba.ar

The aim of this study was to analyze the population pharmacokinetics of oxcarbazepine (OCBZ) measuring the serum level of its active metabolite, monohydroxylated oxcarbazepine (MHD). We studied a group of patients with symptomatic and cryptogenic epilepsy treated with OCBZ monotherapy orally, at least for 3 weeks. The mean doses, age and weight of the patients were 17.9 +/- 7.8 mg/kg/day, 35.6 +/- 16.4 years and 70.3 +/- 19.2 kg, respectively. Blood samples were taken before the first morning dose of OCBZ and MHD levels were determined by HPLC. A linear relationship was found between OCBZ dose and MHD serum level (r = 0.844, p < 0.001). The MHD serum concentration (mg/l) can be predicted as 0.85 x OCBZ dose (mg/kg). There was a significant correlation between observed and predicted MHD concentrations for each patient. The mean MHD clearance (Cl/F) calculated was 4.05 +/- 1.69 l/h, with a coefficient variation of 41%. It was independent of dose, age and weight and followed a non normal distribution. The half-life of MHD was 10.50 +/- 3.17 hours. The influence of other antiepileptic drugs on MHD pharmacokinetics was analyzed by comparing the Cl/F medians from groups of patients receiving concomitant drugs with OCBZ monotherapy group where no significant differences were found. The results can be used to estimate a priori OCBZ doses, in order to individualize the treatment.

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Epilepsia 2000 Dec;41(12):1597-607
Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy.
Barcs G, Walker EB, Elger CE, Scaramelli A, Stefan H, Sturm Y, Moore A, Flesch G, Kramer L, D'Souza J
Orszagos Pszichiatriai es Neurologiai Intezet, Budapest, Hungary.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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Nervenarzt 2000 Oct;71(10):849-55
[Oxcarbazepine (Trileptal). An effective and well tolerated new drug as first choice in treatment of focal seizures].
[Article in German]
Schmidt D, Elger CE
Arbeitsgruppe Epilepsieforschung, Berlin. dbschmidt@t-online.de

Oxcarbazepin (OXC; 10,11-dihydro-10-oxo-5H-dibenz-[b,f]azepin-5-carboxamid, trade name Trileptal) is a new antiepileptic drug for treatment of mono- and adjunctive therapy of partial seizures with or without secondary generalization for adults and children above 6 years of age. It was developed through structural variation of carbamazepine. Extensive postmarketing use includes more than 200,000 patient years. The mechanism of action mainly involves blockage of sodium currents. The recommended daily starting dose of oxcarbazepin for both mono- and adjunctive treatment is 8-10 mg/kg (600 mg/day for adults) in two doses and can be titrated according to clinical benefit up to 2400 mg/day. Oxcarbazepin undergoes reductive metabolism at its keto moiety to form MHD, which is glucuronidated and excreted in the urine, with minimal involvement of the hepatic cytochrome P450-dependent enzymes. Thus, OXC has limited drug interactions and does not require slow titration, allowing for better tolerability. Oxcarbazepin compares favorably to presently available new anticonvulsants of the second generation for two reasons: it is available immediately for both mono- and adjunctive therapy in adults and children, and extensive postmarketing experience from many countries is already available. In addition, OXC has been thoroughly tested in an unusually large clinical development program and been shown to be similarly effective as standard antiepileptic drugs.

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Pharmacotherapy 2000 Aug;20(8 Pt 2):152S-158S
Safety and efficacy of oxcarbazepine: results of randomized, double-blind trials.
Beydoun A
University of Michigan Medical Center, Ann Arbor 48109, USA. Beydoun@umich.edu

Oxcarbazepine is approved as monotherapy and adjunctive therapy for partial seizures with and without secondarily generalized seizures in adults and as adjunctive therapy for partial-onset seizures in children aged 4-16 years. The clinical development of oxcarbazepine is different from the newer antiepileptic drugs (AEDs) in the extent and concordance of results across clinical trials. The safety and efficacy of oxcarbazepine was evaluated in adjunctive therapy trials, in comparative monotherapy trials with classic AEDs in adults and children with newly diagnosed epilepsy, in monotherapy therapeutic failure design trials in patients with refractory partial seizures, and in trigeminal neuralgia and affective disorder. The results of oxcarbazepine in treating epilepsy are discussed.

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Cochrane Database Syst Rev 2000;(3):CD002028
Oxcarbazepine add-on for drug-resistant partial epilepsy.
Castillo S, Schmidt DB, White S
University Department of Neurological Science, 2nd floor - Clinical Science Centre for Research & Education, Lower Lane, Liverpool, Merseyside, UK, L9 7LJ. castillochile@yahoo.com

BACKGROUND: Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30 % develop refractory epilepsy, especially those with partial seizures. In this review we summarise the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy.OBJECTIVES: To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group's trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field. SELECTION CRITERIA: Randomized, placebo-controlled, double-blind, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50 % or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention to treat. Summary odds ratios were estimated for each outcome. MAIN RESULTS: Overall Odds Ratio (OR) (95 % Confidence Interval (CIs)) for 50 % or greater reduction in seizure frequency compared to placebo 2.96 (2.20,4.00). Treatment withdrawal OR (95 % CIs) compared to placebo 2.17 (1.59,2.97). Side effects: OR (99 % CIs) compared to placebo, ataxia 2.93(1.72,4.99); dizziness 3.05 (1.99, 4. 67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine. REVIEWERS' CONCLUSIONS: Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy, both in adults and children. However, trials reviewed were of relatively short duration, and provide no evidence about the long term effects of oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with other epilepsy types.

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Neurology 2000 Jun 27;54(12):2245-51
Oxcarbazepine monotherapy for partial-onset seizures: a multicenter, double-blind, clinical trial.
Beydoun A, Sachdeo RC, Rosenfeld WE, Krauss GL, Sessler N, Mesenbrink P, Kramer L, D'Souza J
University of Michigan Medical Center, Ann Arbor, MI 48109, USA.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) 2,400 mg/day versus OXC 300 mg/day monotherapy in patients with medically refractory partial epilepsy. BACKGROUND: OXC is primarily metabolized by reductase enzymes and, consequently, has a low propensity to inhibit or induce oxidative enzymes and a minimal potential for drug-drug interactions. The efficacy of OXC as monotherapy was shown in several comparative trials in patients with newly diagnosed epilepsy and in hospitalized patients undergoing evaluation for epilepsy surgery. METHODS: A multicenter, double-blind, randomized, parallel-group trial design was chosen to assess the antiepileptic efficacy of OXC as monotherapy in a refractory epilepsy patient population. Outpatients aged 12 years or older with inadequately controlled partial seizures, with or without secondarily generalized seizures, were enrolled. Patients finished the trial by completing the double-blind phase or by meeting one of four predefined exit criteria: a twofold increase in partial seizure frequency in any 28-day period relative to baseline; a twofold increase in the highest consecutive 2-day partial seizure frequency relative to baseline; occurrence of a single generalized seizure if none occurred during the 6 months prior to randomization; or prolongation or worsening of generalized seizure duration or frequency requiring intervention. Adverse events (AEs), vital signs, and clinical laboratory tests were evaluated. RESULTS: The percentage of patients meeting one of the exit criteria was significantly lower (p < 0.0001) for the OXC 2400 mg/day group (14/34; 41%) than the OXC 300 mg/day group (42/45; 93%). In addition, there was a significant difference in time to exit in favor of the OXC 2400 mg/day group (p = 0.0001). In the intent-to-treat analysis, 12% of patients in the OXC 2400 mg/day group were seizure-free compared with none in the 300 mg/day group. OXC was well-tolerated, with dizziness, fatigue, somnolence, and nausea being the most frequent AEs. Most of these AEs were transient and rated as mild to moderate in intensity. CONCLUSION: OXC is safe and effective in the treatment of patients with partial epilepsy previously receiving treatment with other antiepileptic drugs. The results of this trial are consistent with previous monotherapy trials with OXC.

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Neurol Neurochir Pol 2000;33 Suppl 1:215-20
[No title available].
[Article in Polish]
Kluczynski A
Katedra i Klinika Neurologii Wieku Rozwojowego AM w Poznaniu.

A comparative study was conducted to evaluate the efficacy and tolerabilitity of oxcarbazepine administration in patients with a diagnosed intractable epilepsy with simple partially and complex seizures secondarily generalised. There were 12 patients aged between 2-23 treated in Outpatients' Neurological Department for Children and Adolescents in Poznan. Oxcarbazepine was applied as an add-on therapy in all patients. The drug was administered in 3 daily dose. The doses of oxcarbazepine were evaluated as well as the occurrence of adverse effects was recorded. Four patients presented over 50% reduction of seizures. During the whole period of observation there was no occurrence of adverse effects associated with the inclusion of oxcarbazepine as add-on drug.

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Neurology 1999 Mar 10;52(4):732-7
Oxcarbazepine: double-blind, randomized, placebo-control, monotherapy trial for partial seizures.
Schachter SC, Vazquez B, Fisher RS, Laxer KD, Montouris GD, Combs-Cantrell DT, Faught E, Willmore LJ, Morris GL, Ojemann L, Bennett D, Mesenbrink P, D'Souza J, Kramer L
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA. Sschacht@bidmc.harvard.edu

OBJECTIVE: To evaluate the efficacy and safety of oxcarbazepine in a placebo-control trial. METHODS: A multicenter, double-blind, randomized, placebo-control, two-arm parallel group, monotherapy design was used to compare oxcarbazepine administered 1,200 mg twice daily to placebo in hospitalized patients with refractory partial seizures, including simple and complex partial seizures and partial seizures evolving to secondarily generalized seizures. Patients exited the trial after completing the 10-day double-blind treatment phase or after experiencing four partial seizures, two new-onset secondarily generalized seizures, serial seizures, or status epilepticus, whichever came first. RESULTS: Analysis of the primary efficacy variable--time to meeting one of the exit criteria--showed a statistically significant effect in favor of oxcarbazepine (p = 0.0001). The secondary efficacy variables--percentage of patients who met one of the exit criteria (p = 0.0001) and total partial seizure frequency per 9 days during the double-blind treatment (p = 0.0001)--were also statistically significant in favor of oxcarbazepine. CONCLUSION: These results demonstrate that oxcarbazepine given as monotherapy is effective and safe for the treatment of partial seizures in this paradigm.

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Epilepsy Res 1997 Mar;26(3):451-60
A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy.
Christe W, Kramer G, Vigonius U, Pohlmann H, Steinhoff BJ, Brodie MJ, Moore A
Department of Neurology, University Hospital Rudolf-Virchow, Berlin, Germany.

Oxcarbazepine (OXC) has been licensed as monotherapy and add-on treatment in epilepsy patients with partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in a double-blind, randomized, parallel-group comparison with sodium valproate (VPA). Two-hundred and forty-nine patients with either PS or generalized seizures aged 15-65 years were randomized. After a retrospective baseline, patients were randomized to VPA or OXC in a 1:1 ratio. The double-blind treatment phase was divided into two periods, flexible titration and maintenance. The titration period was 8 weeks followed by 48 weeks of individualized, maintenance treatment given three times a day. Three primary analyses were used to assess efficacy, tolerability, and the association between the two. In the efficacy analyses comprising 212 patients who had at least one seizure assessment during the maintenance period, no statistically significant difference at the 5% level was found between the treatment groups. Sixty patients (56.6%) in the OXC group and 57 patients (53.8%) in the VPA group were seizure free during maintenance treatment. Fifty-two patients in the OXC group discontinued treatment prematurely (15 because of tolerability reasons) compared to 41 patients in the VPA group (ten due to tolerability reasons). There was no statistically significant difference between the treatment groups with respect to the total number of premature discontinuations or those due to adverse experiences. This trial provides support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS.

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Epilepsy Res 1997 Jun;27(3):195-204
A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy.
Bill PA, Vigonius U, Pohlmann H, Guerreiro CA, Kochen S, Saffer D, Moore A
Department of Neurology, Wentworth Hospital, Durban, South Africa.

In the last 5 years oxcarbazepine (OXC) has been registered in many countries for use as first-line and add-on treatment for partial seizures with or without secondarily generalized seizures (PS) and generalized tonic-clonic seizures without partial onset (GTCS). Its use as monotherapy in adults with newly diagnosed epilepsy was investigated in this double-blind, randomized, parallel-group comparison with phenytoin (PHT). A total of 287 adult patients, with either PS or GTCS, were randomized. After retrospective baseline assessment, patients were randomized to OXC or PHT in a 1:1 ratio. The double-blind treatment phase was divided into two periods: a flexible titration period of 8 weeks, followed by 48 weeks of maintenance treatment. In the efficacy analyses, no statistically significant differences were found between the treatment groups. Seventy patients (59.3%) in the OXC group and 69 (58.0%) in the PHT group were seizure-free during the maintenance period. A total of 56 of the patients in the OXC group discontinued treatment prematurely (five because of tolerability reasons) compared to 61 in the PHT group (16 for tolerability reasons). The number of premature discontinuations due to adverse experiences showed a statistically significant difference in favour of OXC. There was no statistically significant difference between the groups with respect to the total number of premature discontinuations. This trial provides further support for the efficacy and safety of OXC as first-line treatment in adults with PS and GTCS. In addition, the results show that OXC has significant advantages over PHT in terms of tolerability.

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