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The Annals of Pharmacotherapy Oct 2021
Topics: Anticonvulsants; Carbamazepine; Factor Xa Inhibitors; Humans; Oxcarbazepine; Rivaroxaban
PubMed: 33511853
DOI: 10.1177/1060028021990374 -
Toxicology Letters Oct 2021Certain medicines including anticancer drugs, NSAIDs and antiepileptic drugs are known to cause drug-induced nephropathy. For example, antiepileptic drugs such as...
Certain medicines including anticancer drugs, NSAIDs and antiepileptic drugs are known to cause drug-induced nephropathy. For example, antiepileptic drugs such as carbamazepine (CBZ) and valproic acid have been reported to cause damage to the proximal tubular cells. Although there has been a great deal of research concerning the nephrotoxicity of CBZ, little is known about that of oxcarbazepine (OXC), a derivative of CBZ. To investigate the molecular mechanism underlying renal proximal tubular cell death caused by OXC, we examined alterations in the gene expression profile of NRK-52E proximal tubular cells during OXC exposure. DNA microarray analysis revealed that the levels of genes related to mitotic processes including chromosomal and cytoplasmic segregation, progression to G2/M phase, and formation of the mitotic spindle are increased after exposure to 50 μM OXC for 6 h. Cell cycle analysis by flow cytometry showed that OXC at concentrations between 25 and 100 μM induces G2/M arrest. We also found that OXC significantly increases histone H3 phosphorylation, indicative of mitotic cells. These results imply that OXC induces cell cycle arrest at the mitotic phase. Immunofluorescence analysis showed monopolar spindles, which are formed in response to centrosome separation defects, in OXC-treated cells. We also show that OXC suppresses the phosphorylation of PLK1, which is involved not only in the activation of the kinesin family of motor proteins for centrosome separation and bipolar spindle assembly, but also in the cleavage of centrosomal proteins. Thus, our results indicate that OXC inhibits centrosome separation by reducing the activation of PLK1, which leads to the formation of an abnormal spindle and induces mitotic catastrophe and apoptosis in NRK-52E cells.
Topics: Animals; Anticonvulsants; Apoptosis; Cells, Cultured; Epilepsy; Humans; Kidney Tubules, Distal; Mitosis; Models, Animal; Oxcarbazepine; Rats
PubMed: 34333065
DOI: 10.1016/j.toxlet.2021.07.018 -
Turkish Neurosurgery 2022To systematically evaluate the medication safety and effectiveness of Oxcarbazepine (OXC) and carbamazepine (CBZ) for the treatment of post-stroke epilepsy (PSE). (Meta-Analysis)
Meta-Analysis
AIM
To systematically evaluate the medication safety and effectiveness of Oxcarbazepine (OXC) and carbamazepine (CBZ) for the treatment of post-stroke epilepsy (PSE).
MATERIAL AND METHODS
We searched Medline and other databases to identify the randomized controlled trials (RCTs) that compare the efficacies of OXC and CBZ in treating PSE. Two authors extracted and analyzed the data independently with Revman 5.3 software. The Q-test and I2 were used to test the statistical heterogeneity. The fixed or random effect models were selected according to heterogeneity.
RESULTS
Eight RCTs that include 671 patients were involved in this study. The meta-analyses result showed that the overall efficiency of OXC was significantly better than that of CBZ (OR=4.55, 95% confidence interval (CI) (3.04?6.81)), the overall adverse events (OR=0.27, 95% CI (0.18?0.42), and the incidence of vomiting (OR=0.28, 95% CI (0.09?0.85)) of OXC was significantly less than that of CBZ. No significant differences in the incidence of rash (OR=0.45, 95% CI (0.19?1.07)), lethargy (OR=0.49, 95% CI (0.16?1.45)), and dizziness (OR=0.51, 95% CI (0.20?1.35)) were detected between OXC and CBZ.
CONCLUSION
OXC seems to be superior to CBZ in the treatment of PSE, with higher efficacy, and safety than the latter. However, more research on OXC and CBZ in the treatment of PSE is required in the later stage due to the sample size limitation of our study.
Topics: Anticonvulsants; Carbamazepine; Epilepsy; Humans; Oxcarbazepine
PubMed: 34936076
DOI: 10.5137/1019-5149.JTN.34664-21.3 -
European Journal of Neurology Sep 2016The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse... (Review)
Review
The use of carbamazepine (CBZ) and oxcarbazepine (OXC) as first-line antiepileptic drugs in the treatment of focal epilepsy is limited by hyponatremia, a known adverse effect. Hyponatremia occurs in up to half of people taking CBZ or OXC and, although often assumed to be asymptomatic, it can lead to symptoms ranging from unsteadiness and mild confusion to seizures and coma. Hyponatremia is probably due to the antidiuretic properties of CBZ and OXC that are, at least partly, explained by stimulation of the vasopressin 2 receptor/aquaporin 2 pathway. No known genetic risk variants for CBZ- and OXC-induced hyponatremia exist, but likely candidate genes are part of the vasopressin water reabsorption pathway.
Topics: Animals; Anticonvulsants; Carbamazepine; Humans; Hyponatremia; Oxcarbazepine; Pharmacogenetics
PubMed: 27333872
DOI: 10.1111/ene.13069 -
Epilepsia Dec 2022Thyroid hormone abnormalities have been linked to antiseizure medications (ASMs). Oxcarbazepine is considered safer than carbamazepine because it induces the hepatic...
OBJECTIVE
Thyroid hormone abnormalities have been linked to antiseizure medications (ASMs). Oxcarbazepine is considered safer than carbamazepine because it induces the hepatic cytochrome P450 metabolic enzymes less than the carbamazepine does. However, limited data exist for the influence of oxcarbazepine on thyroid function in children and adolescents. The objective of this study was to determine the effect of oxcarbazepine on thyroid function in these patients.
METHODS
A total of 162 pediatric patients with epilepsy who started oxcarbazepine for the first time between April 2003 and May 2020 were enrolled. The longitudinal effects of oxcarbazepine for thyroid functions were confirmed using general estimating equations.
RESULTS
Serum triiodothyronine (T3), thyroxine (T4), and free thyroxine (fT4) levels decreased significantly during 5 years of follow-up (all p's < .001). In particular, T3 and fT4 levels were reduced steeply in the first 2 years of oxcarbazepine treatment. There was no significant change in thyroid-stimulating hormone during oxcarbazepine treatment.
SIGNIFICANCE
Serum T3, T4, and fT4 levels decreased significantly during oxcarbazepine use, and this change was maintained during the treatment period. In patients receiving oxcarbazepine, it is recommended that periodic thyroid function testing should be performed, especially within the first 2 years after starting this ASM. Our results indicate that oxcarbazepine-induced hypothyroidism does not appear to be accompanied by a significant increase in TSH, and consequently might be missed if TSH alone is monitored as a measure of thyroid dysfunction.
Topics: Humans; Child; Adolescent; Oxcarbazepine; Thyroid Gland; Epilepsy
PubMed: 36073252
DOI: 10.1111/epi.17407 -
Epilepsia Mar 2021To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced... (Observational Study)
Observational Study
OBJECTIVE
To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced hyponatremia (COIH).
METHODS
We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia.
RESULTS
A total of 1370 people using CBZ or OXC were identified, of whom 410 had at least one episode of hyponatremia. We checked for symptoms related to the use of CBZ and OXC in 710 people (410 with and 300 without hyponatremia) and found relevant information in 688. Adverse effects occurred in 65% of people with hyponatremia compared to 21% with normal sodium levels (odds ratio [OR] 7.5, P ≤ .001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia (P ≤ .001). Significant predictors of adverse effects were the drug (OXC vs CBZ), and the number of concomitant anti-seizure medications. Dizziness (28% vs 6%), tiredness (22% vs 7%), instability (19% vs 3%), and diplopia (16% vs 4%) were reported more often in the hyponatremia group than in patients with normal levels.
SIGNIFICANCE
People with COIH had a 7-fold increased risk of developing adverse effects during treatment. Clinicians should consider ascertainment of sodium levels in patients taking CBZ and OXC and act upon findings.
Topics: Adult; Anticonvulsants; Carbamazepine; Dizziness; Epilepsy; Fatigue; Female; Humans; Hyponatremia; Male; Middle Aged; Oxcarbazepine; Retrospective Studies; Sodium
PubMed: 33576502
DOI: 10.1111/epi.16828 -
JAMA Neurology Jun 2023Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points...
IMPORTANCE
Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.
OBJECTIVE
To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023.
EXPOSURES
Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth.
MAIN OUTCOMES AND MEASURES
The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported.
RESULTS
Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07).
CONCLUSIONS AND RELEVANCE
Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.
Topics: Pregnancy; Child; Female; Male; Adolescent; Humans; Child, Preschool; Valproic Acid; Lamotrigine; Incidence; Levetiracetam; Topiramate; Prenatal Exposure Delayed Effects; Prospective Studies; Anticonvulsants; Epilepsy; Oxcarbazepine; Carbamazepine; Attention Deficit Disorder with Hyperactivity
PubMed: 37067807
DOI: 10.1001/jamaneurol.2023.0674 -
Epilepsia 1994Controlled studies of oxcarbazepine (OCBZ) and the largest of the open studies of OCBZ were reviewed. The overall results indicated that OCBZ has the same clinical... (Review)
Review
Controlled studies of oxcarbazepine (OCBZ) and the largest of the open studies of OCBZ were reviewed. The overall results indicated that OCBZ has the same clinical effect as carbamazepine (CBZ) but causes fewer adverse effects. Studies of allergic toxicity seem to indicate that OCBZ may be tolerated in the majority of patients developing allergy towards CBZ. We concluded that OCBZ is a drug of first choice for the treatment of epilepsy.
Topics: Anticonvulsants; Carbamazepine; Clinical Trials as Topic; Epilepsy; Humans; Oxcarbazepine
PubMed: 8156976
DOI: 10.1111/j.1528-1157.1994.tb05942.x -
JAMA Neurology Apr 2022During pregnancy in women with epilepsy, lower blood concentrations of antiseizure medications can have adverse clinical consequences. (Observational Study)
Observational Study
IMPORTANCE
During pregnancy in women with epilepsy, lower blood concentrations of antiseizure medications can have adverse clinical consequences.
OBJECTIVE
To characterize pregnancy-associated concentration changes for several antiseizure medications among women with epilepsy.
DESIGN, SETTING, AND PARTICIPANTS
Enrollment in this prospective, observational cohort study, Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), occurred from December 19, 2012, to February 11, 2016, at 20 US sites. Enrolled cohorts included pregnant women with epilepsy and nonpregnant control participants with epilepsy. Inclusion criteria were women aged 14 to 45 years, an intelligence quotient greater than 70 points, and, for the cohort of pregnant women, a fetal gestational age younger than 20 weeks. A total of 1087 women were assessed for eligibility; 397 were excluded and 230 declined. Data were analyzed from May 1, 2014, to June 30, 2021.
EXPOSURE
Medication plasma concentrations in women taking monotherapy or in combination with noninteracting medications. The cohort of pregnant women was monitored through 9 months post partum, with similar time points for control participants.
MAIN OUTCOMES AND MEASURES
Dose-normalized concentrations were calculated as total or unbound plasma medication concentrations divided by total daily dose. Phlebotomy was performed during 4 pregnancy study visits and 3 postpartum visits for the pregnant women and 7 visits over 18 months for control participants. The primary hypothesis was to test pregnancy changes of dose-normalized concentrations from nonpregnant postpartum samples compared with those of control participants.
RESULTS
Of the 351 pregnant women and 109 control participants enrolled in MONEAD, 326 pregnant women (median [range] age, 29 [19-43] years) and 104 control participants (median [range] age, 29 [16-43] years) met eligibility criteria for this analysis. Compared with postpartum values, dose-normalized concentrations during pregnancy were decreased by up to 56.1% for lamotrigine (15.60 μg/L/mg to 6.85 μg/L/mg; P < .001), 36.8% for levetiracetam (11.33 μg/L/mg to 7.16 μg/L/mg; P < .001), 17.3% for carbamazepine (11.56 μg/L/mg to 7.97 μg/L/mg; P = .03), 32.6% for oxcarbazepine (11.55 μg/L/mg to 7.79 μg/L/mg; P < .001), 30.6% for unbound oxcarbazepine (6.15 μg/L/mg to 4.27 μg/L/mg; P < .001), 39.9% for lacosamide (26.14 μg/L/mg to 15.71 μg/L/mg; P < .001), and 29.8% for zonisamide (40.12 μg/L/mg to 28.15 μg/L/mg; P < .001). No significant changes occurred for unbound carbamazepine, carbamazepine-10,11-epoxide, and topiramate, although a decrease was observed for topiramate (29.83 μg/L/mg to 13.77 μg/L/mg; P = .18). Additionally, compared with dose-normalized concentrations from control participants, pregnancy dose-normalized median (SE) concentrations decreased significantly by week of gestational age: carbamazepine, -0.14 (0.06) μg/L/mg (P = .02); carbamazepine unbound, -0.04 (0.01) μg/L/mg (P = .01); lacosamide, -0.23 (0.07) μg/L/mg (P < .001); lamotrigine, -0.20 (0.02) μg/L/mg (P < .001); levetiracetam, -0.06 (0.03) μg/L/mg (P = .01); oxcarbazepine, -0.14 (0.04) μg/L/mg (P < .001); oxcarbazepine unbound, -0.11 (0.03) μg/L/mg (P < .001); and zonisamide, -0.53 (0.14) μg/L/mg (P < .001) except for topiramate (-0.35 [0.20] μg/L/mg per week) and carbamazepine-10,11-epoxide (0.02 [0.01] μg/L/mg).
CONCLUSIONS AND RELEVANCE
Study results suggest that therapeutic drug monitoring should begin early in pregnancy and that increasing doses of these anticonvulsants may be needed throughout the course of pregnancy.
Topics: Adult; Anticonvulsants; Carbamazepine; Epilepsy; Female; Humans; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Pregnancy; Prospective Studies; Topiramate; Zonisamide
PubMed: 35157004
DOI: 10.1001/jamaneurol.2021.5487 -
Epilepsy & Behavior : E&B Feb 2010
Topics: Adult; Anticonvulsants; Carbamazepine; Dose-Response Relationship, Drug; Epilepsy; Humans; Male; Oxcarbazepine; Sexual Dysfunctions, Psychological
PubMed: 20089459
DOI: 10.1016/j.yebeh.2009.12.022