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Seizure Jan 2002
Comparative Study
Topics: Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Humans; Oxcarbazepine
PubMed: 11888266
DOI: 10.1053/seiz.2002.0673 -
Journal of Managed Care Pharmacy : JMCP 2006Clinical practice guidelines (CPGs) are intended not only to provide supportive information for health care providers but also to act as a guide for health care policy... (Comparative Study)
Comparative Study Review
OBJECTIVE
Clinical practice guidelines (CPGs) are intended not only to provide supportive information for health care providers but also to act as a guide for health care policy decisions. However, extant CPGs do not always reach the same conclusions. The objective of this study was to compare recommendations for initial pharmacological treatment of new-onset epilepsy in adults as stated within published CPGs.
METHODS
We performed a systematic review of CPGs, which were published by prominent national organizations between January 2000 and June 2005, regarding the initial pharmacological treatment of epilepsy in adults.
RESULTS
Five CPGs and 1 evidence report were identified that focus on pharmaceutical management in epilepsy. The 3 guidelines most relevant to the question of new-onset epilepsy treatment in adults were developed by the American Academy of Neurology (AAN), Scottish Intercollegiate Guidelines Network (SIGN), and National Institute for Health and Clinical Excellence (NICE). AAN recommends the use of both recently introduced antiepileptic drugs (AEDs: gabapentin, lamotrigine, topiramate, and oxcarbazepine) and standard agents (carbamazepine, phenytoin, valproic acid/divalproex, and phenobarbital) in newly diagnosed epilepsy, i.e., a nontiered approach. Alternatively, NICE recommends using newer AEDs (lamotrigine, topiramate, and oxcarbazepine) only in patients who derive no benefit from older agents--a tiered approach. SIGN notes that all AEDs licensed for monotherapy have similar efficacy in newly diagnosed epilepsy--a recommendation for a nontiered approach. The newer AEDs (lamotrigine and oxcarbazepine) are recommended as first-line initial treatment as are standard agents (carbamazepine and valproic acid/divalproex). The NICE guideline includes economic and quality-of-life evidence in their recommendations while AAN and SIGN do not. In these regards, current data fails to show superiority for newer agents.
CONCLUSION
In the past 5 years, several CPGs have been published in epilepsy management. Only 3 guidelines have explicit recommendations for initial pharmacological treatment of adults with epilepsy. With some variation regarding which medications are recommended from each group, all CPGs promote standard and newer AEDs as having similar clinical efficacy. Until efficacy, quality of life, or cost data for the newer agents demonstrates a superior outcome, older AEDs remain viable options as first-line for monotherapy in newly diagnosed patients and may provide cost benefits over newer agents.
Topics: Adult; Anticonvulsants; Epilepsy; Humans; Practice Patterns, Physicians'; United States
PubMed: 16420108
DOI: 10.18553/jmcp.2006.12.1.55 -
Seizure Aug 2018Oxcarbazepine is known as an effective first-line monotherapy for pediatric focal epilepsy. Lamotrigine has also been reported to have similar efficacy to and better... (Comparative Study)
Comparative Study Observational Study
PURPOSE
Oxcarbazepine is known as an effective first-line monotherapy for pediatric focal epilepsy. Lamotrigine has also been reported to have similar efficacy to and better tolerability than carbamazepine. Therefore, the effectiveness of oxcarbazepine and lamotrigine monotherapies was compared in patients with pediatric focal epilepsy.
METHOD
A total of 116 patients in pediatric patients with partial epilepsy received lamotrigine (n = 43) or oxcarbazepine (n = 73) monotherapy. The clinical characteristics, seizure outcomes, reasons for drug discontinuation, retention rate and adverse effects were evaluated for each drug.
RESULTS
Oxcarbazepine was more commonly used than lamotrigine (69/73 vs. 23/43) as initial monotherapy. Lamotrigine showed better efficacy than oxcarbazepine in terms of the seizure outcome more than 12 months (P<0.05). Oxcarbazepine and lamotrigine showed similar tolerability in terms of the retention rate, drug discontinuation and adverse effects. The rates of successful discontinuation were similar for patients receiving these drug as initial monotherapy (P > 0.05). The seizure outcome was much better for lamotrigine than for oxcarbazepine in patients with normal MRI findings and normal development (P = 0.001, P = 0.01). The retention rate was high in patients with MRI abnormalities or developmental delay in the lamotrigine group. The choice of lamotrigine was the only independent variable that predicted a seizure-free state, even after correcting for clinical variables (OR = 4.80, P = 0.013).
CONCLUSIONS
Lamotrigine was superior to oxcarbazepine monotherapy because of its greater effectiveness in treating pediatric focal epilepsy. Lamotrigine can be selected as a first-line monotherapy in patients with or without abnormal MRI findings or delayed development.
Topics: Adolescent; Anticonvulsants; Carbamazepine; Child; Child, Preschool; Epilepsies, Partial; Female; Follow-Up Studies; Humans; Lamotrigine; Logistic Models; Male; Oxcarbazepine; Patient Dropouts; Treatment Outcome; Triazines
PubMed: 29957441
DOI: 10.1016/j.seizure.2018.06.013 -
Epilepsia Sep 1997Voltage-gated calcium currents play important roles in controlling neuronal excitability. They also contribute to the epileptogenic discharge, including seizure... (Review)
Review
Voltage-gated calcium currents play important roles in controlling neuronal excitability. They also contribute to the epileptogenic discharge, including seizure maintenance and propagation. In the past decade, selective calcium channel blockers have been synthesized, aiding in the analysis of calcium channel subtypes by patch-clamp recordings. It is still a matter of debate whether whether any of the currently available antiepileptic drugs (AEDs) inhibit these conductances as part of their mechanism of action. We tested oxcarbazepine, lamotrigine, and felbamate and found that they consistently inhibited voltage-activated calcium currents in cortical and striatal neurons at clinically relevant concentrations. Low micromolar concentrations of GP 47779 (the active metabolite of oxcarbazepine) and lamotrigine reduced calcium conductances involved in the regulation of transmitter release. In contrast, felbamate blocked nifedipine-sensitive conductances at concentrations significantly lower than those required to modify N-methyl-D-aspartate (NMDA) responses or sodium currents. Aside from contributing to AED efficacy, this mechanism of action may have profound implications for preventing fast-developing cellular damage related to ischemic and traumatic brain injuries. Moreover, the effects of AEDs on voltage-gated calcium signals may lead to new therapeutic strategies for the treatment of neurodegenerative disorders.
Topics: Animals; Anticonvulsants; Calcium Channels; Carbamazepine; Drug Design; Epilepsy; Felbamate; Humans; Lamotrigine; Mice; Neuroprotective Agents; Oxcarbazepine; Phenylcarbamates; Propylene Glycols; Rats; Triazines
PubMed: 9579933
DOI: 10.1111/j.1528-1157.1997.tb01477.x -
International Journal of Molecular... Jun 2024The objective of this study was to assess the impact of acute and chronic treatment with oxcarbazepine on its anticonvulsant activity, neurological adverse effects, and...
The objective of this study was to assess the impact of acute and chronic treatment with oxcarbazepine on its anticonvulsant activity, neurological adverse effects, and protective index in mice. Oxcarbazepine was administered in four protocols: once or twice daily for one week (7 × 1 or 7 × 2) and once or twice daily for two weeks (14 × 1 or 14 × 2). A single dose of the drug was employed as a control. The anticonvulsant effect was evaluated in the maximal electroshock test in mice. Motor and long-term memory impairment were assessed using the chimney test and the passive avoidance task, respectively. The concentrations of oxcarbazepine in the brain and plasma were determined via high-performance liquid chromatography. Two weeks of oxcarbazepine treatment resulted in a significant reduction in the anticonvulsant (in the 14 × 1; 14 × 2 protocols) and neurotoxic (in the 14 × 2 schedule) effects of this drug. In contrast, the protective index for oxcarbazepine in the 14 × 2 protocol was found to be lower than that calculated for the control. No significant deficits in memory or motor coordination were observed following repeated administration of oxcarbazepine. The plasma and brain concentrations of this anticonvulsant were found to be significantly higher in the one-week protocols. Chronic treatment with oxcarbazepine may result in the development of tolerance to its anticonvulsant and neurotoxic effects, which appears to be dependent on pharmacodynamic mechanisms.
Topics: Animals; Oxcarbazepine; Mice; Anticonvulsants; Electroshock; Male; Disease Models, Animal; Seizures; Brain; Memory, Long-Term; Carbamazepine; Avoidance Learning
PubMed: 38928457
DOI: 10.3390/ijms25126751 -
RSC Advances Feb 2021Structurally related carbamazepine (CBZ) and oxcarbazepine (OX) are two of the most commonly used antipsychotic drugs. The main impurities of CBZ, as described in both...
Appraisal of the greenness profile of a chromatographic method for the simultaneous estimation of carbamazepine and oxcarbazepine, along with two potential impurities and three formulation excipients.
Structurally related carbamazepine (CBZ) and oxcarbazepine (OX) are two of the most commonly used antipsychotic drugs. The main impurities of CBZ, as described in both the USP and the BP, are iminodibenzyl (IMD) and iminostilbene (IST). Meanwhile, for non-pharmacopeial OX, the declared impurities include CBZ and IST. Prescribed oral suspensions of CBZ and OX contain additives including methyl paraben (MP), propyl paraben (PP) and sorbic acid (SA) as preservatives. An HPTLC method was introduced and developed for resolving the interference between CBZ, OX, their impurities, and the suspension additives in a single run, in addition to their quantitation with a high sensitivity that satisfies the USP requirements for the detection and quantitation of drug impurities. In the developed HPTLC method, CBZ and OX were measured in the range of 40-4000 ng per band, while IMD, IST, MP, PP and SA were in the range of 20-2000 ng per band, using a mixture of hexane : ethylacetate : formic acid : acetic acid (8 : 2 : 0.5 : 0.3, by volume) and UV scanning at 254 nm. The greenness profile of the method was evaluated by two different tools, the analytical Eco-Scale and the Green Analytical Procedure Index (GAPI), then a comparison between their results was conducted. This is the first time that the studied drugs, along with their impurities and suspension additives, were analyzed by a HPTLC method in a single run and within the limits required by the USP guidelines.
PubMed: 35423303
DOI: 10.1039/d0ra10521j -
Revista de NeurologiaTo review and update the most important information concerning the mechanism of action, efficacy, safety and clinical use of oxcarbazepine (OXC), one of the new... (Review)
Review
AIM
To review and update the most important information concerning the mechanism of action, efficacy, safety and clinical use of oxcarbazepine (OXC), one of the new antiepileptic drugs (AED).
DEVELOPMENT
In humans, OXC is rapid and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). OXC is a molecule derived from carbamazepine (CBZ), but these two drugs showed differences in their mechanism of action. OXC pharmacokinetics presents advantage over CBZ: in contrast with CBZ, OXC does not show autoinduction, the OXC dose-MHD serum concentration relationship displays a linear kinetics over the therapeutic dose range, and the frequency of drug-drug interactions is lower. So, we can establish standardized dose regimen and titration schedules in monotherapy and polytherapy. OXC shows better tolerability and safety than CBZ, in part at consequence of absence of 10-11-epoxi metabolites from CBZ. The better safety profile of OXC is reflected in less adverse drug reactions incidence, lower patient risk in overdosing, absence of reported cases of agranulocytosis or aplastic anemia, scarce cases founded of cardiotoxicity and lower risk of neurotoxicity. Common side effects of OXC are nausea, dizziness, vomiting, fatigue, diplopia and somnolence. During treatment with OXC must pay attention to development of hyponatremia, neurotoxicity or cutaneous hypersensitivity reactions. OXC is approved for use in infants. OXC is indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures with or without secondarily generalized seizures in adults and in children age 6 and over.
CONCLUSIONS
OXC showed important advances on safety and pharmacological properties for administration to adults and infants. OXC has similar clinical antiepileptic efficacy than older AED in the treatment of partial seizures, and it is recommended as a treatment of choice for partial seizures by several international guidelines.
Topics: Anticonvulsants; Carbamazepine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Epilepsy; Humans; Molecular Structure; Oxcarbazepine; Placebos
PubMed: 16450324
DOI: No ID Found -
Molecules (Basel, Switzerland) Sep 2022A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in...
Development and Validation of a Highly Sensitive and Rapid LC-MS Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring.
A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, ) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing-Bablok regression coefficients and Bland-Altman plots showed that the developed LC-MS method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.
Topics: Carbamazepine; Chromatography, High Pressure Liquid; Chromatography, Liquid; Drug Monitoring; Epilepsy; Humans; Oxcarbazepine; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 36080439
DOI: 10.3390/molecules27175670 -
Seizure Dec 2020
Topics: Anticonvulsants; Carbamazepine; Dibenzazepines; Humans
PubMed: 33334544
DOI: 10.1016/j.seizure.2020.10.026 -
Seizure Mar 1995The low therapeutic index of established antiepileptic drugs coupled with a better understanding of the pathophysiology of seizure production has led to the development... (Review)
Review
The low therapeutic index of established antiepileptic drugs coupled with a better understanding of the pathophysiology of seizure production has led to the development of a range of new therapeutic agents for the treatment of epilepsy. In this review, the three drugs recently licensed in the UK (vigabatrin, lamotrigine and gabapentin) are profiled, together with several of the more promising up-and-coming compounds (oxcarbazepine, felbamate, tiagabine, stiripentol, remacemide and topiramate). Future avenues for clinical research in the pharmacological management of the epilepsies involve their rational use both singly and in combination.
Topics: Acetates; Amines; Anticonvulsants; Cyclohexanecarboxylic Acids; Drug Approval; Drug Interactions; Drug Therapy, Combination; Epilepsy; Gabapentin; Humans; Lamotrigine; Product Surveillance, Postmarketing; Treatment Outcome; Triazines; Vigabatrin; gamma-Aminobutyric Acid
PubMed: 7788108
DOI: 10.1016/s1059-1311(05)80074-3