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British Journal of Clinical Pharmacology Dec 2017Oxcarbazepine is an antiepileptic drug with an activity mostly due to its monohydroxy derivative metabolite (MHD). A parent-metabolite population pharmacokinetic model...
AIMS
Oxcarbazepine is an antiepileptic drug with an activity mostly due to its monohydroxy derivative metabolite (MHD). A parent-metabolite population pharmacokinetic model in children was developed to evaluate the consistency between the recommended paediatric doses and the reference range for trough concentration (C ) of MHD (3-35 mg l ).
METHODS
A total of 279 plasma samples were obtained from 31 epileptic children (age 2-12 years) after a single dose of oxcarbazepine. Concentration-time data were analysed with Monolix 4.3.2. The probability to obtain C between 3-35 mg l was determined by Monte Carlo simulations for doses ranging from 10 to 90 mg kg day .
RESULTS
A parent-metabolite model with two compartments for oxcarbazepine and one compartment for MHD best described the data. Typical values for oxcarbazepine clearance, central and peripheral distribution volume and distribution clearance were 140 l h 70 kg , 337 l 70 kg , 60.7 l and 62.5 l h , respectively. Typical values for MHD clearance and distribution volume were 4.11 l h 70 kg and 54.8 l 70 kg respectively. Clearances and distribution volumes of oxcarbazepine and MHD were related to body weight via empirical allometric models. Enzyme-inducing antiepileptic drugs (EIAEDs) increased MHD clearance by 29.3%. Fifty-kg children without EIAEDs may need 20-30 mg kg day instead of the recommended target maintenance dose (30-45 mg kg day ) to obtain C within the reference range. By contrast, 10-kg children with EIAEDs would need 90 mg kg day instead of the maximum recommended dose of 60 mg kg day .
CONCLUSION
This population pharmacokinetic model of oxcarbazepine supports current dose recommendations, except for 10-kg children with concomitant EIAEDs and 50-kg children without EIAEDs.
Topics: Age Factors; Anticonvulsants; Area Under Curve; Biotransformation; Carbamazepine; Child; Child, Preschool; Computer Simulation; Epilepsy; Female; Humans; Hydroxylation; Male; Models, Biological; Monte Carlo Method; Oxcarbazepine
PubMed: 28771787
DOI: 10.1111/bcp.13392 -
Behavioural Neurology 1990Altogether 235 patients with newly diagnosed epilepsy were randomly allocated to treatment with either oxcarbazepine (OXC) or carbamazepine (CBZ) in a double-blind...
Altogether 235 patients with newly diagnosed epilepsy were randomly allocated to treatment with either oxcarbazepine (OXC) or carbamazepine (CBZ) in a double-blind multicentre trial. After a titration phase of 4-8 weeks the optimum individual dose of trial medication was determined and treatment with this dose was continued for another 48 weeks.The results of the study indicate that there is no significant difference in seizure frequency between OXC and CBZ; no correlation was found between the therapeutic effect and EEG in either treatment group. OXC caused significantly (p = 0.04) fewer "severe" side-effects than CBZ. Global evaluation of tolerability showed a trend towards better tolerability of OXC. There way no correlation between either efficacy or tolerability and serum trough levels of the investigational drugs. Clinically relevant abnormal laboratory test findings were observed in two patients, both on CBZ.In conclusion, OXC is a major anti-epileptic drug, which is as effective as CBZ in the treatment of partial seizures and generalized convulsions. With fewer side-effects than CBZ, it represents a valuable alternative particularly in patients who develop side-effects which prevent optimum seizure control.
PubMed: 24487083
DOI: 10.3233/BEN-1990-31S105 -
Seizure Mar 2008The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (OCs) pose potential risks of un-intended... (Review)
Review
The occurrence of bi-directional drug interactions between antiepileptic drugs (AEDs) and combined oral contraceptives (OCs) pose potential risks of un-intended pregnancy and as well as seizure deterioration. It is well established that several of the older AEDs (carbamazepine, phenytoin and phenobarbital), are strong inducers of the hepatic cytochrome P450 (CYP) 3A4 enzyme system, and are associated with increased the risk of contraceptive failure. In addition, it is demonstrated that also some of the newer AEDs, oxcarbazepine and topiramate influence on the pharmacokinetics of OCs, which is thought to be due to a more selective induction of subgroups of the hepatic enzyme system. Estrogens containing OCs induce the glucuronosyltransferase and may reduce the plasma levels and the effect of AEDs cleared by glucuronidation. This has been most intensively studied for lamotrigine but also other AEDs, which undergoes glucuronidation processes, such as valproate and oxcarbazepine, may be affected by OCs. The magnitude of the drug-drug interactions show in general wide inter-individual variability and the change in the elimination rate is often unpredictable and can be influenced by a number of co-variants such as co-medication of other drugs, as well as genetic and environmental factors. It is therefore recommended that change in OC use is assisted by AED monitoring whenever possible.
Topics: Animals; Anticonvulsants; Contraceptive Agents; Drug Interactions; Humans
PubMed: 18206393
DOI: 10.1016/j.seizure.2007.11.012 -
International Journal of Molecular... Dec 2023Experimental studies reveal that caffeine (trimethylxanthine) at subconvulsive doses, distinctly reduced the anticonvulsant activity of numerous antiseizure medications... (Review)
Review
Experimental studies reveal that caffeine (trimethylxanthine) at subconvulsive doses, distinctly reduced the anticonvulsant activity of numerous antiseizure medications (ASMs) in rodents, oxcarbazepine, tiagabine and lamotrigine being the exceptions. Clinical data based on low numbers of patients support the experimental results by showing that caffeine (ingested in high quantities) may sharply increase seizure frequency, considerably reducing the quality of patients' lives. In contrast, this obviously negative activity of caffeine was not found in clinical studies involving much higher numbers of patients. ASMs vulnerable to caffeine in experimental models of seizures encompass carbamazepine, phenobarbital, phenytoin, valproate, gabapentin, levetiracetam, pregabalin and topiramate. An inhibition of R-calcium channels by lamotrigine and oxcarbazepine may account for their resistance to the trimethylxanthine. This assumption, however, is complicated by the fact that topiramate also seems to be a blocker of R-calcium channels. A question arises why large clinical studies failed to confirm the results of experimental and case-report studies. A possibility exists that the proportion of patients taking ASMs resistant to caffeine may be significant and such patients may be sufficiently protected against the negative activity of caffeine.
Topics: Humans; Lamotrigine; Oxcarbazepine; Caffeine; Topiramate; Anticonvulsants; Seizures; Calcium Channels
PubMed: 38139396
DOI: 10.3390/ijms242417569 -
Epilepsia Jul 2017To ascertain possible determinants of carbamazepine (CBZ)- and oxcarbazepine (OXC)-induced hyponatremia in a large cohort of people with epilepsy.
OBJECTIVE
To ascertain possible determinants of carbamazepine (CBZ)- and oxcarbazepine (OXC)-induced hyponatremia in a large cohort of people with epilepsy.
METHODS
We collected data on serum sodium levels in people with epilepsy who were attending a tertiary epilepsy center while on treatment with CBZ or OXC. We defined hyponatremia as Na+ ≤134 mEq/L and severe hyponatremia as Na+ ≤128 mEq/L.
RESULTS
We identified 1,782 people who had used CBZ (n = 1,424) or OXC (n = 358), of whom 50 were treated with both drugs. Data on sodium level measurements were available in 1,132 on CBZ and in 289 on OXC. Hyponatremia occurred in 26% of those taking CBZ and 46% of those taking OXC. This was severe in 7% in the CBZ group and 22% in the OXC group. Hyponatremia was symptomatic in 48% and led to admissions in 3%. Age over 40 years, high serum levels of CBZ and OXC, and concomitant use of other antiepileptic drugs were the main risk factors for hyponatremia in both treatment groups. Female patients on OXC were at a higher risk than male patients of hyponatremia. The risk of hyponatremia on CBZ was significantly associated with the risk of hyponatremia on OXC within a subgroup that used both drugs consecutively.
SIGNIFICANCE
Hyponatremia is a common problem in people taking CBZ or OXC. Regular ascertainment of sodium levels in those taking either drug is recommended and results should be acted on.
Topics: Adult; Anticonvulsants; Carbamazepine; Cohort Studies; Drug Therapy, Combination; Epilepsy; Female; Humans; Hyponatremia; Male; Middle Aged; Oxcarbazepine; Risk Factors; Sex Factors; Sodium
PubMed: 28542738
DOI: 10.1111/epi.13777 -
Frontiers in Medicine 2023Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug,...
BACKGROUND
Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN.
METHODS
Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023.
RESULTS
A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported.
CONCLUSION
Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.
PubMed: 37881633
DOI: 10.3389/fmed.2023.1232969 -
Experimental and Therapeutic Medicine Dec 2020This study aimed to investigate the clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram in treating patients with epilepsy and depressive...
Comparison of clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram, and impact on prognostic quality of life in treating patients with epilepsy and depressive disorder.
This study aimed to investigate the clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram in treating patients with epilepsy and depressive disorder, and their influence on the prognostic quality of life. A total of 108 patients with epilepsy and depression were selected as research participants. Among them, 53 patients were treated by oxcarbazepine combined with escitalopram (group A) and 55 patients were treated by lamotrigine combined with escitalopram (group B). Following six-month treatment, efficacy, epilepsy frequency and duration, Hamilton Depression Rating (HAMD) and Montgomery-Asberg Depression Rating (MADRS) scores, adverse reactions, improvement of electroencephalogram (EEG) epileptic discharge, quality of life, 1-year drug retention rate and withdrawal reasons of the two groups were compared. There was no remarkable difference in the total efficacy rate between both groups. The number and duration of epileptic seizures, improvement of EEG epileptic discharge and quality of life in the two groups significantly improved after treatment, with no marked difference. HAMD and MADRS scores of patients from group B were significantly lower after treatment compared with those of patients from group A. The incidence rate of adverse reactions in group B was dramatically lower compared with group A, and the 1-year drug retention rate of group B was dramatically higher compared with that in group A. Both oxcarbazepine and lamotrigine combined with escitalopram exhibited good efficacy in patients with epilepsy and depressive disorder, and they may effectively improve the prognostic quality of life of patients. Lamotrigine combined with escitalopram presented with a better antidepressant effect and safety, with higher patient tolerance.
PubMed: 33093884
DOI: 10.3892/etm.2020.9275 -
Proceedings (Baylor University. Medical... Oct 2020The primary aims of this study were to determine if oxcarbazepine is a safely tolerated option for treatment of psychiatric symptoms in children and whether its use...
The primary aims of this study were to determine if oxcarbazepine is a safely tolerated option for treatment of psychiatric symptoms in children and whether its use facilitates dose modification of other psychotropic medications. A retrospective chart review was completed using data extracted from the electronic medical record of a large outpatient child psychiatry clinic. A total of 507 of 740 children prescribed oxcarbazepine for psychiatric indications for 3 months or more had adequate data to assess clinical responses and medication outcomes. Most patients prescribed oxcarbazepine experienced clinically significant control of irritability/anger, mood stabilization, aggressive outbursts, impulsivity, or anxiety, with over 80% achieving at least maintenance symptom control. In all, 51% and 25% fully discontinued second- or third-generation antipsychotic or antidepressant medication, respectively, after starting oxcarbazepine; 8% discontinued oxcarbazepine for nonresponse, while 9% stopped oxcarbazepine because of emergent side effects. In patients fully discontinuing or reducing the second- or third-generation antipsychotic dose by 50% or more, improvements in body mass index were observed. Oxcarbazepine may prove to be an appropriate alternative to antipsychotic and antidepressant medications for treating psychiatric symptoms in children and adolescents. In particular, it may be a more metabolically neutral psychotropic medication.
PubMed: 33456141
DOI: 10.1080/08998280.2020.1826259 -
The Cochrane Database of Systematic... Jan 2008Some studies have suggested that oxcarbazepine has a role in preventing episode recurrence in bipolar affective disorder. This review attempted to investigate the... (Review)
Review
BACKGROUND
Some studies have suggested that oxcarbazepine has a role in preventing episode recurrence in bipolar affective disorder. This review attempted to investigate the existing evidence from randomised controlled trials for its use in the maintenance treatment of this illness.
OBJECTIVES
To review the efficacy of oxcarbazepine, relative to placebo and other agents, in the prevention of affective episodes of bipolar affective disorder. The efficacy of oxcarbazepine was considered in terms of episode recurrence, general and social functioning. Adverse effects, overall acceptability to participants and mortality were also considered.
SEARCH STRATEGY
CCDANCTR-Studies and CCDANCTR-References were searched on 7/11/2007. Medline, CENTRAL, EMBASE and PsycINFO were searched in March 2007. Specialist journals and conference proceedings were handsearched. Reference lists of relevant papers and major textbooks of affective disorder were checked. Authors, experts in the field and pharmaceutical companies were contacted requesting information on published or unpublished trials.
SELECTION CRITERIA
Randomised controlled trials comparing oxcarbazepine with placebo or alternative agents, where the stated intent of intervention was the maintenance treatment of bipolar affective disorder were sought. Participants with bipolar disorder, male and female, of all ages, were included.
DATA COLLECTION AND ANALYSIS
Data were extracted from the original reports individually by two review authors. The methodological quality of included studies was assessed individually by two review authors. The main outcomes were the efficacy of oxcarbazepine maintenance treatment in preventing or attenuating further episodes of bipolar affective disorder (including its efficacy in rapid cycling disorder), the acceptability of oxcarbazepine treatment to participants, the prevalence of side-effects, and mortality, if any, on oxcarbazepine treatment. Where appropriate, data concerning outcome measures and adverse effects were to be extracted from the studies and analysed using Review Manager software.
MAIN RESULTS
Two randomised controlled trials were found that met the methodological criteria for inclusion in the review. However, they did not report data with sufficient clarity to allow their confident extraction for inclusion in the meta-analysis. Findings from the two studies were presented descriptively.
AUTHORS' CONCLUSIONS
There is an insufficient methodologically rigorous evidence base to provide guidance on the use of oxcarbazepine in the maintenance treatment of bipolar disorder. Given the need for more efficacious therapeutic agents, there is a need for good quality randomised controlled trials examining the therapeutic potential of this and related agents in bipolar disorder.
Topics: Antimanic Agents; Bipolar Disorder; Carbamazepine; Humans; Lithium Compounds; Oxcarbazepine; Randomized Controlled Trials as Topic; Secondary Prevention
PubMed: 18254071
DOI: 10.1002/14651858.CD005171.pub2 -
The American Journal of Managed Care Jul 2001For many years, epileptologists had few choices for treating seizures. Within the past 20 years several "new generation" antiepileptic drugs (AEDs) were introduced. The... (Review)
Review
For many years, epileptologists had few choices for treating seizures. Within the past 20 years several "new generation" antiepileptic drugs (AEDs) were introduced. The most recent additions include oxcarbazepine, levetiracetam, and zonisamide. New agents have been shown in clinical trials to offer similar efficacy compared with older, more established AEDs, but the new agents offer important improvements in safety. Although clinical trials to specifically measure the efficacy of the new AEDs in treating idiopathic generalized epilepsy are rare, the new agents have demonstrated efficacy in treating generalized tonic-clonic convulsions. Data for treatment of Lennox-Gastaut syndrome indicate a clear effect with lamotrigine or topiramate and possibly some effect with zonisamide and levetiracetam. Studies of juvenile myoclonic epilepsy and absence seizures suggest that zonisamide, lamotrigine, topiramate, and levetiracetam may be effective. Each of the new AEDs is effective in controlling partial seizures. These agents may also be appropriate choices for newly diagnosed patients or those whose conditions are refractory to treatment. In clinical trials, patients who are refractory to treatment are often given escalated doses to gain effect, but higher doses also result in more adverse events and higher withdrawal rates. Generally, the higher the dose, the greater the odds of withdrawal, with the exception of levetiracetam, which is not associated with increased withdrawal rates at high doses. Newly diagnosed patients are likely to be controlled with the first therapy given to them. It is therefore important to select an agent with the best safety, efficacy, and tolerability profile possible.
Topics: Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Epilepsies, Partial; Epilepsy; Epilepsy, Tonic-Clonic; Felbamate; Humans; Lamotrigine; Oxcarbazepine; Phenylcarbamates; Polypharmacy; Propylene Glycols; Randomized Controlled Trials as Topic; Treatment Outcome; Triazines; United States
PubMed: 11474769
DOI: No ID Found