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Journal of Chemical Neuroanatomy Jan 2020This study assessed apoptosis in the offspring of rats exposed to oxcarbazepine (OXC) from day 7 to 15 of gestation. Three groups of pregnant Wistar rats were used: 1)...
This study assessed apoptosis in the offspring of rats exposed to oxcarbazepine (OXC) from day 7 to 15 of gestation. Three groups of pregnant Wistar rats were used: 1) Control, treated with saline solution; 2) treated with 100 mg/kg OXC; 3) treated with 100 mg/kg of carbamazepine (CBZ, as a positive control for apoptosis); the route of administration was intragastric. Apoptosis was detected at three postnatal ages using the TUNEL technique in the CA1, and CA3 regions of the hippocampus and in the dentate gyrus (DG); neurogenesis was assessed in the DG using an antibody against doublecortin. The litter characteristics were recorded. OXC increased apoptosis in all regions (p < 0.01) at the three ages evaluated. Lamination disruption occurred in CA1 and CA3 due to the neuron absence and to ectopic neurons; there were also malformations in the dorsal lamina of the DG in 38% and 25% of the pups born from rats treated with OXC and CBZ respectively. CBZ also increased apoptosis. No clear effect on neurogenesis in the DG was observed. The size of the litter was smaller (p < 0.01) in the experimental groups. Nineteen-day OXC fetuses had low weight (p < 0.01), but 21 and 30 postnatal days old CBZ and OXC pups were overweight (p < 0.01). The results demonstrate that OXC administered during gestation is pro-apoptotic, alters the cytoarchitecture of the hippocampus, reduces litter size, and probably influences postnatal weight. We provide evidence of the proapoptotic effect of CBZ when administered early in gestation.
Topics: Animals; Anticonvulsants; Apoptosis; Doublecortin Protein; Female; Hippocampus; Neurogenesis; Neurons; Oxcarbazepine; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar
PubMed: 31794794
DOI: 10.1016/j.jchemneu.2019.101729 -
Annals of Clinical and Translational... Aug 2021Allergic reactions are common reasons for withdrawal of oxcarbazepine treatment in patients with epilepsy. However, some patients are not responsive to other antiseizure...
Allergic reactions are common reasons for withdrawal of oxcarbazepine treatment in patients with epilepsy. However, some patients are not responsive to other antiseizure medications. Herein, two pediatric patients with epilepsy and allergic to oxcarbazepine to whom oxcarbazepine therapy was successfully reintroduced are described. The reintroduction strategy used in this study was simple, feasible, and suitable for the reintroduction of oxcarbazepine in pediatric patients with epilepsy.
Topics: Anticonvulsants; Child; Drug Hypersensitivity; Epilepsy; Humans; Infant; Male; Oxcarbazepine
PubMed: 34181315
DOI: 10.1002/acn3.51415 -
Journal of Clinical Pharmacy and... Feb 2022Oxcarbazepine (OXC) is an antiepileptic drug. Patients suffering from chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73 m...
WHAT IS KNOWN AND OBJECTIVE
Oxcarbazepine (OXC) is an antiepileptic drug. Patients suffering from chronic kidney disease with an estimated glomerular filtration rate below 30 ml/min/1.73 m require dose adjustments for OXC.
CASE SUMMARY
A 31-year-old man was admitted with a history of diplopia, ataxia and dizziness attacks that had disappeared after a regular haemodialysis sessions for three months. Medical history was remarkable for primary antiphospholipid syndrome (APS). However, no signs of new-onset APS-related neurological involvement were present. Then, it was revealed that the patient had been using 2400 mg/day of OXC for four months, despite the prescription of half of this dose. Serum OXC level was 50 mcg/ml (reference: 3-35 mcg/ml) before a regular haemodialysis session. All symptoms disappeared in a few days after reducing to 1200 mg/day and never recurred.
WHAT IS NEW AND CONCLUSION
We reported a chronic OXC intoxication in a patient on maintenance haemodialysis. To the best of our knowledge, it is the first chronic OXC intoxication case in the literature. It could be related to episodic removal of OXC and its metabolites via haemodialysis. Consequently, dose modification of drugs is a pivotal point in haemodialysis patients. Chronic drug intoxications must be kept in mind in haemodialysis patients with unexplained symptoms.
Topics: Adult; Anticonvulsants; Antiphospholipid Syndrome; Glomerular Filtration Rate; Humans; Male; Oxcarbazepine; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 34322888
DOI: 10.1111/jcpt.13504 -
Indian Journal of Pharmacology 2021
Topics: Aged; Anticonvulsants; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Lupus Erythematosus, Systemic; Male; Oxcarbazepine
PubMed: 34854412
DOI: 10.4103/ijp.IJP_445_20 -
Chinese Medical Journal Jul 2020Benign epilepsy with centrotemporal spikes (BECTS) is the most common type of childhood idiopathic focal epilepsy. BECTS is associated with pervasive cognitive deficits...
BACKGROUND
Benign epilepsy with centrotemporal spikes (BECTS) is the most common type of childhood idiopathic focal epilepsy. BECTS is associated with pervasive cognitive deficits and behavior problems. While seizures can be easily controlled, it is crucial to select anti-epileptic drugs that do not impair cognition, do not cause psychosocial effects, and improve the quality of life. Previous studies showed effects of oxcarbazepine (OXC) monotherapy on the cognitive and psychosocial profiles of patients with BECTS. Here, we studied the effects of OXC monotherapy on the neuropsychologic profiles and quality of life in patients with BECTS in China.
METHODS
Thirty-one patients aged 6 to 12 years newly diagnosed with BECTS were recruited. A psychometric assessment was performed before and during the follow-up of OXC monotherapy with Cognitive Computerized Task Battery, Depression Self-Rating Scale for children, Screen for Child Anxiety Related Emotional Disorders, and Quality of Life in Epilepsy-31 (QOLIE-31). The results of the assessments were compared to explore the effect of OXC monotherapy in patients with BECTS.
RESULTS
Thirty children with BECTS completed the study. Five of ten cognitive test scores improved after treatment via OXC monotherapy, including visual tracing (F = 14.480, P < 0.001), paired associated learning (language) (F = 6.292, P < 0.001), paired associated learning (number) (F = 9.721, P < 0.05), word semantic (F = 6.003, P < 0.05), and simple subtraction (F = 6.229, P < 0.05). Of the neuropsychology data concerning the quality of life, statistically significant improvements were observed in emotion (F = 4.946, P < 0.05), QOLIE-social (F = 5.912, P < 0.05), and QOLIE-total (F = 14.161, P < 0.001).
CONCLUSIONS
OXC is safe and does not impair neuropsychologic functions, with no obvious mood burden on children with BECTS. Most importantly, OXC has positive impacts on children's perception of quality of life, especially in terms of happiness and life satisfaction.
Topics: Child; China; Electroencephalography; Epilepsy, Rolandic; Humans; Neuropsychological Tests; Oxcarbazepine; Quality of Life
PubMed: 32649517
DOI: 10.1097/CM9.0000000000000925 -
Indian Pediatrics Jun 2023A prospective longitudinal study was conducted to assess the Apo B100/A1 ratio as a marker of cardiovascular risk in children with epilepsy aged 5-14 years on long-term...
A prospective longitudinal study was conducted to assess the Apo B100/A1 ratio as a marker of cardiovascular risk in children with epilepsy aged 5-14 years on long-term anti-seizure medication monotherapy with either sodium valproate, oxcarbazepine, or levetiracetam. Apo B100/A1 ratio showed an increase after six months of monotherapy with oxcarbazepine (P=0.05).
Topics: Child; Humans; Oxcarbazepine; Levetiracetam; Valproic Acid; Anticonvulsants; Longitudinal Studies; Prospective Studies; Carbamazepine; Epilepsy
PubMed: 37293912
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2018This is an updated version of the Cochrane Review previously published in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2013. This review is one in a series of Cochrane Reviews investigating pair-wise monotherapy comparisons.Epilepsy is a common neurological condition in which abnormal electrical discharges from the brain cause recurrent unprovoked seizures. It is believed that with effective drug treatment, up to 70% of individuals with active epilepsy have the potential to become seizure-free and go into long-term remission shortly after starting drug therapy with a single antiepileptic drug in monotherapy.Worldwide, phenytoin is a commonly used antiepileptic drug. It is important to know how newer drugs, such as oxcarbazepine, compare with commonly used standard treatments.
OBJECTIVES
To review the time to treatment failure, remission and first seizure with oxcarbazepine compared to phenytoin, when used as monotherapy in people with focal onset seizures or generalised tonic-clonic seizures (with or without other generalised seizure types).
SEARCH METHODS
We searched the following databases on 20 August 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2018), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials comparing monotherapy with either oxcarbazepine or phenytoin in children or adults with focal onset seizures or generalised onset tonic-clonic seizures.
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) review. Our primary outcome was time to treatment failure and our secondary outcomes were time to first seizure post-randomisation, time to six-month and 12-month remission, and incidence of adverse events. We used Cox proportional hazards regression models to obtain trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs), using the generic inverse variance method to obtain the overall pooled HR and 95% CI.
MAIN RESULTS
Individual participant data were available for 480 out of a total of 517 participants (93%), from two out of three included trials. For remission outcomes, a HR of less than one indicated an advantage for phenytoin; and for first seizure and treatment failure outcomes, a HR of less than one indicated an advantage for oxcarbazepine.The results for time to treatment failure for any reason related to treatment showed a potential advantage of oxcarbazepine over phenytoin, but this was not statistically significant (pooled HR adjusted for epilepsy type: 0.78 95% CI 0.53 to 1.14, 476 participants, two trials, moderate-quality evidence). Our analysis showed that treatment failure due to adverse events occurred later on with oxcarbazepine than phenytoin (pooled HR for all participants: 0.22 (95% CI 0.10 to 0.51, 480 participants, two trials, high-quality evidence). Our analysis of time to treatment failure due to lack of efficacy showed no clear difference between the drugs (pooled HR for all participants: 1.17 (95% CI 0.31 to 4.35), 480 participants, two trials, moderate-quality evidence).We found no clear or statistically significant differences between drugs for any of the secondary outcomes of the review: time to first seizure post-randomisation (pooled HR adjusted for epilepsy type: 0.97 95% CI 0.75 to 1.26, 468 participants, two trials, moderate-quality evidence); time to 12-month remission (pooled HR adjusted for epilepsy type 1.04 95% CI 0.77 to 1.41, 468 participants, two trials, moderate-quality evidence) and time to six-month remission (pooled HR adjusted for epilepsy type: 1.06 95% CI 0.82 to 1.36, 468 participants, two trials, moderate-quality evidence).The most common adverse events reported in more than 10% of participants on either drug were somnolence (28% of total participants, with similar rates for both drugs), headache (15% of total participants, with similar rates for both drugs), dizziness (14.5% of total participants, reported by slightly more participants on phenytoin (18%) than oxcarbazepine (11%)) and gum hyperplasia (reported by substantially more participants on phenytoin (18%) than oxcarbazepine (2%)).The results of this review are applicable mainly to individuals with focal onset seizures; 70% of included individuals experienced seizures of this type at baseline. The two studies included in IPD meta-analysis were generally of good methodological quality but the design of the studies may have biased the results for the secondary outcomes (time to first seizure post-randomisation, time to six-month and 12-month remission) as seizure recurrence data were not collected following treatment failure or withdrawal from the study. In addition, misclassification of epilepsy type may have impacted on results, particularly for individuals with generalised onset seizures.
AUTHORS' CONCLUSIONS
High-quality evidence provided by this review indicates that treatment failure due to adverse events occurs significantly later with oxcarbazepine than phenytoin. For individuals with focal onset seizures, moderate-quality evidence suggests that oxcarbazepine may be superior to phenytoin in terms of treatment failure for any reason, seizure recurrence and seizure remission. Therefore, oxcarbazepine may be a preferable alternative treatment than phenytoin, particularly for individuals with focal onset seizures. The evidence in this review which relates to individuals with generalised onset seizures is of low quality and does not inform current treatment policy.We recommend that future trials should be designed to the highest quality possible with regards to choice of population, classification of seizure type, duration of follow-up (including continued follow-up after failure or withdrawal of randomised treatment), choice of outcomes and analysis, and presentation of results.
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy, Tonic-Clonic; Humans; Induction Chemotherapy; Oxcarbazepine; Phenytoin; Proportional Hazards Models; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 30350354
DOI: 10.1002/14651858.CD003615.pub4 -
Der Nervenarzt Oct 2000Oxcarbazepin (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... (Review)
Review
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.
Topics: Adult; Anticonvulsants; Biotransformation; Carbamazepine; Child; Epilepsies, Partial; Humans; Oxcarbazepine; Treatment Outcome
PubMed: 11082818
DOI: 10.1007/s001150050675 -
Epilepsy Research 1988In order to estimate the frequency of hyponatremia in patients treated with oxcarbazepine (OxCZ), a cross-sectional study was carried out. 21 of 41 patients being...
In order to estimate the frequency of hyponatremia in patients treated with oxcarbazepine (OxCZ), a cross-sectional study was carried out. 21 of 41 patients being treated with the drug were found to be hyponatremic (serum sodium levels less than 135 mmol/l). None was found to be hypernatremic (serum sodium levels greater than 145 mmol/l). A non-significant trend towards increasing frequency of hyponatremia with increasing age was observed. Patients treated with dosages above 30 mg/kg/day had a significantly higher risk of becoming hyponatremic.
Topics: Adult; Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Epilepsy; Female; Humans; Hyponatremia; Male; Middle Aged; Oxcarbazepine
PubMed: 3197696
DOI: 10.1016/0920-1211(88)90018-6 -
Neurochemical Research Feb 2002Carbamazepine (CBZ) has been extensively used in the treatment of epilepsy, as well as in the treatment of neuropathic pain and affective disorders. However, the... (Review)
Review
Carbamazepine (CBZ) has been extensively used in the treatment of epilepsy, as well as in the treatment of neuropathic pain and affective disorders. However, the mechanisms of action of this drug are not completely elucidated and are still a matter of debate. Since CBZ is not very effective in some epileptic patients and may cause several adverse effects, several antiepileptic drugs have been developed by structural variation of CBZ, such as oxcarbazepine (OXC), which is used in the treatment of epilepsy since 1990. (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz [b,f]azepine-5-carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz[b,f] azepine-5-carboxamide (BIA 2-024), which were recently developed by BIAL, are new putative antiepileptic drugs, with some improved properties. In this review, we will focus on the mechanisms of action of CBZ and its derivatives, OXC, BIA 2-093 and BIA 2-024. The available data indicate that the anticonvulsant efficacy of these AEDs is mainly due to the inhibition of sodium channel activity.
Topics: Animals; Anticonvulsants; Carbamazepine; Dibenzazepines; Epilepsy; Humans; Oxcarbazepine; Sodium Channel Blockers
PubMed: 11926264
DOI: 10.1023/a:1014814924965