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Epilepsia 1999The success of carbamazepine (CBZ) as a broad-spectrum antiepileptic drug (AED) has led to its use as first-line therapy in children and adults for partial and... (Comparative Study)
Comparative Study Review
The success of carbamazepine (CBZ) as a broad-spectrum antiepileptic drug (AED) has led to its use as first-line therapy in children and adults for partial and generalized tonic-clonic seizures. The limitations of CBZ include toxicity in sensitive individuals, autoinduction, which requires dose adjustment when therapy is initiated, and chronic hepatic induction, producing drug interactions when CBZ is used with AEDs and other drugs that undergo hepatic metabolism. One of two main products of CBZ microsomal metabolism, CBZ-10,11-epoxide (formed by oxidation of the double bond between C-10 and C-11), appears to provide antiepileptic efficacy but contributes significantly to clinical toxicity. The most common adverse effects of CBZ are central nervous system (CNS) symptoms, followed by gastrointestinal, hepatic, endocrine disturbances, and teratogenic effects. Oxcarbazepine (OXC) was developed to provide a compound chemically similar enough to CBZ to mimic its efficacy and overall safety while improving its side-effect profile. Biotransformation of OXC does not involve formation of an epoxide metabolite. Compared with the parent compound, hepatic microsomal enzyme induction and autoinduction are greatly reduced. The clinical efficacy of OXC compares favorably with CBZ in clinical trials. Clinical development of OXC began in Europe. Results of Phase I trials started to appear in the early 1980s. Controlled clinical trials, reported in the mid- to late 1980s, led to approval of OXC in many European countries, and now in over 50 nations around the world. United States multicenter clinical trials have recently been completed, and at this writing the drug is awaiting approval by the FDA. This article reviews the pharmacology, animal data, outcomes of published controlled clinical trials, postmarketing data, adverse experiences, and current recommendations for clinical use of OXC.
Topics: Adult; Animals; Anticonvulsants; Biological Availability; Biotransformation; Carbamazepine; Controlled Clinical Trials as Topic; Disease Models, Animal; Drug Administration Schedule; Drug Interactions; Epilepsy; Humans; Oxcarbazepine; Phenytoin; Treatment Outcome
PubMed: 10530693
DOI: 10.1111/j.1528-1157.1999.tb00918.x -
Medicina (Kaunas, Lithuania) Apr 2021This review is dedicated to the use of carbamazepine and its derivatives oxcarbazepine and eslicarbazepine in bipolar disorder and their relative strengths in treating... (Review)
Review
This review is dedicated to the use of carbamazepine and its derivatives oxcarbazepine and eslicarbazepine in bipolar disorder and their relative strengths in treating and preventing new depressive or manic episodes. This paper will discuss the evidence of their efficacy relative to the polarity of relapse from controlled acute and maintenance/relapse prevention studies in bipolar patients. A Medline search was conducted for controlled acute and maintenance studies with carbamazepine, oxcarbazepine, and eslicarbazepine in bipolar disorder. In addition, abstracts reporting on controlled studies with these medications from key conferences were taken into consideration. Information was extracted from 84 articles on the acute and prophylactic efficacy of the medications under consideration. They all appear to have stronger efficacy in treating acute mania than depression, which also translates to better protection against manic than depressive relapses for carbamazepine. Still, there is a paucity of controlled acute studies on bipolar depression for all and, with the exception of carbamazepine, a lack of long-term monotherapy maintenance data. For eslicarbazepine, the efficacy in bipolar disorder remains largely unknown. Especially with carbamazepine, tolerability issues and drug-drug interactions need to be kept in mind. Two of the medications discussed in this review, carbamazepine and oxcarbazepine, match Class A criteria according to the criteria proposed by Ketter and Calabrese, meaning acute antimanic efficacy, prevention of manic relapses, and not causing or worsening depression.
Topics: Antimanic Agents; Benzodiazepines; Bipolar Disorder; Carbamazepine; Humans; Oxcarbazepine
PubMed: 33946323
DOI: 10.3390/medicina57050433 -
Frontiers in Pharmacology 2023This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). This is an ambispective,...
This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Identifier ChiCTR2300074696.
PubMed: 37711169
DOI: 10.3389/fphar.2023.1189058 -
The Cochrane Database of Systematic... Dec 2017Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several anticonvulsant drugs are used in the management of neuropathic pain. Oxcarbazepine is an anticonvulsant drug closely related to carbamazepine. Oxcarbazepine has been reported to be efficacious in the treatment of neuropathic pain, but evidence from randomised controlled trials (RCTs) is conflicting. Oxcarbazepine is reportedly better tolerated than carbamazepine. This is the first update of a review published in 2013.
OBJECTIVES
To assess the benefits and harms of oxcarbazepine for different types of neuropathic pain.
SEARCH METHODS
On 21 November 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We searched the Chinese Biomedical Retrieval System (January 1978 to November 2016). We searched the US National Institutes of Health (NIH) databases and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials in January 2017, and we wrote to the companies who make oxcarbazepine and to pain experts requesting additional information.
SELECTION CRITERIA
All RCTs and randomised cross-over studies of oxcarbazepine for the treatment of people of any age or sex with any neuropathic pain were eligible. We planned to include trials of oxcarbazepine compared with placebo or any other intervention with a treatment duration of at least six weeks, regardless of administration route and dose.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
Five multicentre, randomised, placebo-controlled, double-blind trials with a total of 862 participants were eligible for inclusion in this updated review. Three trials involved participants with painful diabetic peripheral neuropathy (DPN) (n = 634), one included people with neuropathic pain due to radiculopathy (n = 145), and one, which was newly identified at this update, involved participants with peripheral neuropathic pain of mixed origin (polyneuropathy, peripheral nerve injury or postherpetic neuralgia) (n = 83). Some studies did not report all outcomes of interest. For painful DPN, compared to the baseline, the proportion of participants who reported at least a 50% or 30% reduction of pain scores after 16 weeks of treatment in the oxcarbazepine group versus the placebo group were: at least 50% reduction: 34.8% with oxcarbazepine versus 18.2% with placebo (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.08 to 3.39, number of people needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 41); and at least 30% reduction: 44.9% with oxcarbazepine versus 28.6% with placebo (RR 1.57, 95% CI 1.01 to 2.44; NNTB 6, 95% CI 3 to 114; n = 146). Both results were based on data from a single trial, since two trials that found little or no benefit did not provide data that could be included in a meta-analysis. Although these trials were well designed, incomplete outcome data and possible unblinding of participants due to obvious adverse effects placed the results at a high risk of bias. There was also serious imprecision and a high risk of publication bias. The radiculopathy trial reported no benefit for the outcome 'at least 50% pain relief' from oxcarbazepine. In mixed neuropathies, 19.3% of people receiving oxcarbazepine versus 4.8% receiving placebo had at least 50% pain relief. These small trials had low event rates and provided, at best, low-quality evidence for any outcome. The proportion of people with 'improved' or 'very much improved' pain was 45.9% with oxcarbazepine versus 30.1% with placebo in DPN (RR 1.46, 95% CI 1.13 to 1.88; n = 493; 2 trials; very-low-quality evidence) and 23.9% with oxcarbazepine versus 14.9% with placebo in radiculopathy (RR 1.61, 95% CI 0.81 to 3.20; n = 145).We found no trials in other types of neuropathic pain such as trigeminal neuralgia.Trial reports stated that most adverse effects were mild to moderate in severity. Based on moderate-quality evidence from the three DPN trials, serious adverse effects occurred in 8.3% with oxcarbazepine and 2.5% with placebo (RR 3.65, 95% CI 1.45 to 9.20; n = 634; moderate-quality evidence). The number needed to treat for an additional harmful (serious adverse effect) outcome (NNTH) was 17 (95% CI 11 to 42). The RR for serious adverse effects in the radiculopathy trial was 3.13 (95% CI 0.65 to 14.98, n = 145). The fifth trial did not provide data.More people withdrew because of adverse effects with oxcarbazepine than with placebo (DPN: 25.6% with oxcarbazepine versus 6.8% with placebo; RR 3.83, 95% CI 2.29 to 6.40; radiculopathy: 42.3% with oxcarbazepine versus 14.9% with placebo; RR 2.84, 95% CI 1.55 to 5.23; mixed neuropathic pain: 13.5% with oxcarbazepine versus 1.2% with placebo; RR 11.51, 95% CI 1.54 to 86.15).
AUTHORS' CONCLUSIONS
This review found little evidence to support the effectiveness of oxcarbazepine in painful diabetic neuropathy, neuropathic pain from radiculopathy and a mixture of neuropathies. Some very-low-quality evidence suggests efficacy but small trials, low event rates, heterogeneity in some measures and a high risk of publication bias means that we have very low confidence in the measures of effect. Adverse effects, serious adverse effects and adverse effects leading to discontinuation are probably more common with oxcarbazepine than placebo; however, the numbers of participants and event rates are low. More well-designed, multicentre RCTs investigating oxcarbazepine for various types of neuropathic pain are needed, and selective publication of studies or data should be avoided.
Topics: Analgesics, Non-Narcotic; Carbamazepine; Diabetic Neuropathies; Humans; Neuralgia; Numbers Needed To Treat; Oxcarbazepine; Radiculopathy; Randomized Controlled Trials as Topic
PubMed: 29199767
DOI: 10.1002/14651858.CD007963.pub3 -
Zhongguo Dang Dai Er Ke Za Zhi =... Apr 2015Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used... (Review)
Review
Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.
Topics: Anticonvulsants; Carbamazepine; Exanthema; Humans; Hyponatremia; Oxcarbazepine
PubMed: 25919567
DOI: No ID Found -
Indian Pediatrics Nov 2013A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of... (Review)
Review
NEED AND PURPOSE OF REVIEW
A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of newer anti-epileptic drugs in children.
METHODS USED FOR LOCATING, SELECTING, EXTRACTING AND SYNTHESIZING DATA
MEDLINE search (1966-2013) was performed using terms newer anti-epileptic drugs, Oxcarbazepine, vigabatrin, topiramate, zonisamide, levetiracetam, lacosamide, rufinamide, stiripentol, retigabine, eslicarbazepine, brivaracetam, ganaxolone and perampanel for reports on use in children. Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case series were included. The main data extracted included indications, efficacy and adverse effects in children.
MAIN CONCLUSIONS
Oxcarbazepine is established as effective initial monotherapy for children with partial-onset seizures. Vigabatrin is the drug of choice for infantile spasms associated with tuberous sclerosis. Lamotrigine, levetiracetam and lacosamide are good add-on drugs for patients with partial seizures. Lamotrigine may be considered as monotherapy in adolescent females with idiopathic generalized epilepsy. Levetiracetam is a good option as monotherapy for females with juvenile myoclonic epilepsy. Topiramate is a good add-on drug in patients with epileptic encephalopathies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy.
Topics: Anticonvulsants; Child; Epilepsy; Humans; India
PubMed: 24382900
DOI: 10.1007/s13312-013-0284-9 -
Journal of Neurology Dec 2022Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear. (Review)
Review
BACKGROUND
Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.
OBJECTIVE
To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.
METHODS
We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.
RESULTS
We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.
CONCLUSIONS
Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.
Topics: Adult; Humans; Hyperammonemia; Valproic Acid; Ammonia; Oxcarbazepine; Epilepsy; Risk Factors; Observational Studies as Topic
PubMed: 35907043
DOI: 10.1007/s00415-022-11304-7