Levetiracetam plus Oxcarbazepine Combination Treatment Downregulates Serum Multidrug Resistance Protein 1 Levels and Upregulates Neuropeptide Y Levels in Children with Epilepsy

Abstract The aim of the present study was to investigate the usefulness of multidrug resistance protein 1 (MDR1) and neuropeptide Y (NPY) levels in predicting the efficacy of levetiracetam (LEV) plus oxcarbazepine (OXC) treatment administered to children with epilepsy and to determine their prognosis. Overall, 193 children with epilepsy admitted to the hospital were enrolled and randomly divided into two groups according to different treatment methods: group A (n = 106, treated with LEV plus OXC combination) and group B (n = 87, treated with OXC only). After treatment, compared with group B, group A exhibited a remarkably higher total effective rate and a significantly lower total adverse reaction rate. Areas under the curve for MDR1 and NPY for predicting ineffective treatment were 0.867 and 0.834, whereas those for predicting epilepsy recurrence were 0.916 and 0.829, respectively. Electroencephalography abnormalities, intracranial hemorrhage, neonatal convulsion, premature delivery, and MDR1 and NPY levels were independent risk factors for poor prognosis in children with epilepsy. Serum MDR1 and NPY levels exhibited a high predictive value for early epilepsy diagnosis, treatment efficacy assessment, and prognostication in children with epilepsy treated with LEV plus OXC combination.

Method establishment for content determination of related substances in Oxcarbazepine tablets / 中国药房

OBJECTIVE To establish the method for content determination of related substances in Oxcarbazepine tablets. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted and the separation was performed on ZORBAX Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate solution （pH6.0） （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was 230 nm and column temperature was set at 35 ℃. The sample size was 10 μL. RESULTS The linear ranges of oxcarbazepine and impurity A， B， C， D， E， I， K， L and N were 0.192-1.440， 1.019-7.639， 0.208-1.559， 0.230-1.727， 0.389-2.915， 0.182-1.364， 0.393-2.945， 0.199-1.493， 0.199-1.490 and 0.200- 1.503 μg/mL， respectively （all r＞0.999）. The detection limits were 0.046， 0.037， 0.049， 0.027， 0.077， 0.040， 0.114， 0.054， 0.055 and 0.039 μg/mL. The quantitation limits were 0.152， 0.122， 0.162， 0.090， 0.258， 0.132， 0.380， 0.181， 0.185 and 0.130 μg/mL. RSDs of precision， repeatability， stability （24 h） and durability tests were all lower than 5.0%. The average recoveries were 92.8%-105.6% （RSD≤3.0%， n＝9）. Only impurity K and unknown impurity were detected in the original preparation sample， with a total content of 0.078% to 0.083%； impurities A， B， D， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅰ， with a total content of 0.147% to 0.163%； impurities A， B， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅱ， with a total content of 0.085% to 0.161%. CONCLUSIONS The established method is rapid， sensitive， accurate， stable and durable. It can be used for the content determination of 9 known impurities in Oxcarbazepine tablets.

The assay of monohydroxy carbamazepine, the active metabolite of oxcarbazepine, in human plasma by HPLC / 药学实践杂志

Objective To establish an assay method for monohydroxy carbamazepine, the active metabolite of oxcarbazepine, in human plasma. Methods Ornidazole was used as the internal standard. Plasma samples were processed with methanol and analyzed by HPLC. The column was ZORBAX Eclipse XDB-C18(150 mm×4.6 mm, 5 μm) with the mobile phase of water-acetonitrile (80∶20, V/V) at a flow rate of 1.0 ml/min. Dual wavelength detection is applied. The detection wavelength of monohydroxy carbamazepine was set at 192 nm and ornidazole at 318 nm. Results There was an excellent liner relationship for monohydroxy carbamazepine from 2 to 50 μg/ml(r= 0.998 6). The limit of quantification was 2 μg/ml with the range of accuracy between 95.57% and 100.59%. The RSD of intra-day and inter-day precisions were less than 15%. The average extraction recovery rate of MHC and internal standard were in the range of 89.62% to 98.76%. The RSD of stability was less than 6%. Conclusion This method is specific, sensitive, and easy to operate. It is suitable for the clinical assay of monohydroxy carbamazepine in human plasma.

Prediction of Serum Concentration of Oxcarbazepine in Uygur Children with Epilepsy in Xinjiang Based on Artificial Neural Network / 中国药学杂志

OBJECTIVE: To predict the steady-state serum concentration of oxcarbazepine in Uygur children with epilepsy in Xinjiang by artificial neural network, thus to provide a theoretical basis for individualized administration of oxcarbazepine. METHODS: The steady-state serum concentration of oxcarbazepine was measured in 270 Uygur children with epilepsy in the People's Hospital of Xinjiang Uygur Autonomous Region, and the relevant data was extracted. The prediction model of plasma concentration of oxcarbazepine was constructed by using Matlab (R2018a) programming software and deep learning network. RESULTS: The network parameters of the model were as follows: the initial learning rate was 0.001, the final learning rate was 0.000 1, the momentum coefficient was 0.90, the maximum training times was 1 000, the genetic algebra was 6 000, and the other parameters were default values. The results of model verification showed that among the 45 Uygur children with epilepsy, the prediction errors of 45 oxcarbazepine serum trough concentrations were all less than 10%, and the rate of error of less than 15% was 100.00%. The mean prediction error(MPE) was 0.01% and the mean absolute prediction error(MAE) was 1.21%. The correlation coefficient between the predicted blood concentration and the actual determined concentration was 0.997, and the predicted result was ideal. CONCLUSION: It is feasible to use artificial neural network to predict the serum concentration of oxcarbazepine in Uygur children with epilepsy in Xinjiang. It can be used in the study of individual administration of oxcarbazepine to promote the rational use of oxcarbazepine in clinic.

Effects of low-dose baclofen adjuvant therapy on patients with trigeminal neuralgia and its effects on inflammatory factors and oxidative stress / 中国临床药理学与治疗学

AIM: To study the effect of low-dose baclofen on inflammatory factors and oxidative stress in patients with trigeminal neuralgia. METHODS: A total of 112 patients with trigeminal neuralgia treated in our hospital from Jan. 2017 to Jan. 2019 were selected as the subjects; they were divided into test group (n=56) and control group (n=56) according to random number table method. The control group was treated with oxcarbazepine, while the test group was treated with low-dose baclofen on the basis of the control group; the clinical total effective rate, visual analogue scale (VAS), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) levels and the incidence of adverse reactions were compared between the two groups. RESULTS:The clinical total effective rate of the test group was significantly higher than that of the control group (P0.05). CONCLUSION:Low-dose baclofen adjuvant therapy has good clinical efficacy for patients with trigeminal neuralgia, which can effectively relieve pain, reduce inflammation and oxidative stress.

Observation of Therapeutic Efficacy of Oxcarbazepine Combined with Levetiracetam in the Treatment of Cognitive Dysfunction in Adult Patients with Temporal Lobe Epilepsy / 中国药房

OBJECTIVE：To observe therapuetic effica cy of oxcarbazepine combined with levetiracetam in the treatment of cognitive dysfunction in adult patients with temporal lobe epilepsy. METHODS ：According to inclusion and exclusion criteria ，83 adult patients with temporal lobe epilepsy were collected from neurology department of the First Affiliated Hospital of Kunming Medical University during January 2018 to October 2019，and then divided into control group （39 cases）and observation group （44 cases）. Control group was given Oxcarbazepine tablet with initial dose of 8-10 mg/（kg·d），morning and night ，increased by 5-10 mg/（kg·d）each week according to patient ’s condition ，the maximal dose was 45 mg/（kg·d），lasting for 3 months with the lowest effective treatment dose. Based on treatment of control group ，observation group was additionally given Levetiracetam tablet with initial dose of 5-10 mg/（kg·d），morning and night ，increased by 5-10 mg/（kg·d）each week according to the severity of disease，the total dose was not more than 2 000 mg/d，lasting for 3 months with the lowest effective treatment dose. The event-related potential P 300 at Pz site in 2 groups was measured before and after treatment （including the incubation period of N 1， P2，N2 and P 3 waves，amplitude of P 3 wave）. Webster ’s Adult Intelligence Scale [WAIS-RC ，including verbal IQ （VIQ）， performance IQ （PIQ），full scale IQ （FIQ）scores] and Clinical Memory Scale [CMS ，converting to memory quotient （MQ） score] were adopted. The occurrence of ADR was recorded. RESULTS ：Totally 5 patients of control group and 7 patients of observation group fell off. Finally ，a total of 71 patients participated in the entire study （34 cases in control group and 37 cases in observation group ）. Before treatment ，there was no statistical significance in P 300 at Pz site ，WAIS-RC and CMS between 2 groups （P＞0.05）. Compared with before treatment ，incubation period of N 2 and P 3 waves was shortenedsignificantly in 2 groups，and amplitude of P 3 wave wasincreased significantly after treatment （P＜0.05）；VIQ，FIQ and MQ scores were increased significantly （P＜0.05）. The incubation pe riod of P 2 wave was shortened significantly，and PIQ score was increased significantly in observation group （P＜ 0.05）. Compared with control group ，the shortening degree of incubation period of P 2，P3 waves，rising degree of amplitude of P 3 wave and rising degree of VIQ ，PIQ，FIQ，MQ scores were more bigger after treatment in observation （P＜0.05）. In the control group，there was 1 case of slight rash ，1 case of conscious asthenia ；in the observation group ，there was 1 case of nausea and vomiting，1 case of conscious asthenia ，and 1 case of emotional instability ；no serious ADR was found in 2 groups. CONCLUSIONS：Oxcarbazepine combined with levetiracetam can improve cognitive dysfunction in adult patients with temporal lobe epilepsy ，and the treatment effect is significantly better than oxcarbazepine monotherapy.

Consistency Evaluation on the Dissolution Behavior and Related Indicators between Generic and Original Pre- parations of Oxcarbazepine Scored Tablets / 中国药房

OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.

Study of clinical efficacy, safety and tolerability of low cost branded generic antiepileptic drugs in children and adolescents

Background: Generic substitution is preferred to reduce healthcare costs and improve patient adherence. The review of literature showed that physicians all around the world were not comfortable in prescribing generic medications due to the lack of evidence on their safety and efficacy.Methods: A prospective study was conducted over a period of one year in Pune. The patients were categorized on their age and were assessed for the clinical effectiveness data (no. of breakthrough seizures and seizure free days) and safety data (no. of ADR episodes). The mean number of patients controlled and the frequency of adverse events at the 3rd and 6th month were calculated.Results: Authors assessed 150 newly diagnosed pediatric epileptic patients who received anti-epileptic drug monotherapy for at least 6 months, out of which 46 (30.66%) received Oxcarbazepine and 104 (69.33%) received Sodium Valproate. At the end of 3 months of therapy 140 (93.33%) patients were seizure free and 145 (96.66%) patients were seizure free at the end of 6 months. Adverse effects were observed in 14 (30.43) patients on oxcarbazepine and 26 (25%) patients on sodium valproate. The most common adverse effect was weight gain in 34 (22.66%) patients with both the AEDs.Conclusions: Seizure control was achieved in majority of the patients. In addition to the seizure control, the frequency of adverse effects was few and tolerable by the patients when prescribed with low cost branded generics.

Bilateral Cataract after Taking Oxcarbazepine

PURPOSE: To report a case of bilateral posterior subcapsular cataract after taking oxcarbazepine (Trileptal®, Novartis, Basel, Swiss). CASE SUMMARY: A 19-year-old female visited our clinic with decreased vision in both eyes. Her best-corrected visual acuity was 0.3 in the right eye and 0.5 in the left eye, and slit-lamp examination revealed a bilateral cortical opacity and subcapsular cataract. She had been taking oxcarbazepine for epilepsy for 10 years, which was discontinued 3 years ago. Her mother had undergone cataract surgeries when she was approximately 46 years of age. No other risk factors for cataract were present. CONCLUSIONS: In the present case, bilateral cortical opacity and subcapsular cataract were assumed to be associated with the use of oxcarbazepine. We suggest that oxcarbazepine could induce a cataract and recommend a regular follow-up by a qualified ophthalmologist.

Evaluation of hematologic profile may be needed for patients treated with oxcarbazepine / 소아과

PURPOSE: The major side effects of treatment with oxcarbazepine (OXC) are skin rash and hyponatremia. Hematologic side effects are reported rarely. The aim of this study was to investigate the rate and types of the hematologic side effects of OXC. METHODS: The medical records of 184 patients diagnosed with epilepsy or movement disorder and on OXC monotherapy, at the Department of Pediatrics of Inje University Sanggye Paik Hospital from July 2001 to July 2018, were retrospectively reviewed. RESULTS: Of the 184 patients, 10 (5.4%) developed leukopenia in addition to pancytopenia and 2 (1.0%) developed pancytopenia. Leukopenia developed in 11 days to 14 years after OXC administration and was more frequent in males than in females (male vs. female, 9 vs. 1; Fisher exact test, P0.05, t-test). CONCLUSION: OXC-induced leukopenia is not rare and may result in pancytopenia. Patients being treated with OXC should be regularly monitored for abnormal complete blood count profiles.

A case series on drug induced hyponatremia: uncommon adverse effect of commonly used drugs

Older patients suffering from depression and psychosis have markedly increased since last decade. So, has the use of antidepressants and antipsychotics. The prevalence of hyponatremia due to these drugs is common in general as well as psychiatric practice. It may also lead to life threatening morbidity and mortality. Loss of renal function, polypharmacy, dementia and other conditions of advanced age can either exacerbate the severity of hyponatremia or mask its onset. In this case series, total four cases were reported of hyponatremia and drugs causing it were escitalopram, quetiapine, tianeptine and oxcarbazepine. Due to polypharmacy, a chance of hyponatremia was more in these patients. Patients received infusion of hypertonic saline with salt added diet to treat hyponatremia. Symptoms of hyponatremia were improved after the treatment. In all four cases, WHO and Naranjo’s causality assessment revealed ‘possible’ causal relationship with the prescribed drug. Prescribers should be aware of such adverse effect due to these drugs.

Effects of Antiepileptic Drugs on Language Abilities in Benign Epilepsy of Childhood with Centrotemporal Spikes

BACKGROUND AND PURPOSE: This study is to assess the responsiveness of electroencephalography (EEG) abnormalities and their effects on language ability after initiating different types of antiepileptic therapy in children with newly diagnosed benign epilepsy of childhood with centrotemporal spikes (BECTS). METHODS: The records of patients newly diagnosed with BECTS (n=120; 69 males) were reviewed retrospectively. The patients were randomly treated with lamotrigine, oxcarbazepine, or topiramate monotherapy, and underwent at least two EEG and standardized language tests. Effects were compared using Pearson’s chi-square tests and paired t-tests. RESULTS: The recurrence rates for seizures in the lamotrigine, topiramate, and oxcarbazepine groups were 19.4%, 21.7%, and 11.4%, respectively, while complete or partial recovery (as indicated by EEG) occurred in 32%, 39%, and 16% of the patients. Patients in the lamotrigine group showed significant improvements in all parameters assessed by the Test of Language Problem Solving Abilities, except for ‘determining cause.’ Patients in the oxcarbazepine group also showed improvements, except for ‘making inferences’ (p < 0.05). Most linguistic index scores were worse in the topiramate group except for Mean Length of Utterance in Words. Patients in the lamotrigine and oxcarbazepine groups showed significant improvements in the receptive language test (p < 0.05). EEG improvements were not related to language ability. CONCLUSIONS: The improvements in language and problem-solving performance in children with BECTS were greater for lamotrigine and oxcarbazepine than for topiramate. However, EEG remission did not imply that language function would be improved after the treatments.

Effects of Oxcarbazepine combined with Levetiracetam treatment on electroencephalography and serum levels of S-100β, glial fibrillary acidic protein in children with epilepsy / 中华实用儿科临床杂志

Objective@#To explore the effects of Oxcarbazepine combined with Levetiracetam treatment on electroencephalography (EEG) and serum levels of S-100β, glial fibrillary acidic protein (GFAP) in children with epilepsy.@*Methods@#One hundred and ten children with epilepsy who were admitted to Zhumadian Central Hospital from March 2016 to May 2017 were selected as research subjects.The random number table method was used to divide 55 patients into combined group (treated with Oxcarbazepine plus Levetiracetam) and 55 patients in control group (only treated with Oxcarbazepine). The clinical efficacy, EEG background activity, serum S-100β and GFAP levels were compared between the 2 groups after treatment.@*Results@#The control rate of the combined group was 69.09%, the markedly effective was 18.18%, the effective was 9.09%, and ineffective was 3.64%; the control group had a control rate of 52.73%, markedly effective 20.00%, effective 20.00%, and ineffective 7.27%, respectively.The differences between the 2 groups were statistically significant (Z=-2.012, P=0.044). Before and after treatment, the background activity of EEG in both groups was dominated by alpha wave activity.There was no significant difference in the activity rate of alpha wave, theta wave and delta wave between the 2 groups (all P>0.05). Before treatment, there was no significant difference in serum S-100β and GFAP levels between the 2 groups (all P>0.05). After treatment, serum S-100β [(0.415±0.086) μg/L, (0.473±0.091) μg/L], GFAP [(2.60±0.44) ng/L, (2.93±0.40) ng/L] in the combined group and the control group were significantly lower than before treatment, and the differences were statistically significant (t=6.339, 6.703, 3.001, 3.364, all P<0.05). After treatment, serum S-100β and GFAP levels in the combined group were significantly lower than those in the control group, and the differences were statistically significant (t=3.435, 4.116, all P<0.05).@*Conclusions@#Oxcarbazepine combined with Levetiracetam is superior to Oxcarbazepine alone in the treatment of children with epilepsy, as it can reduce the levels of S-100β and GFAP and is worthy of clinical application.

Population pharmacokinetics of oxcarbazepine in Chinese epilepsy patients / 药学学报

Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10,11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of UGT2B7 c.802T>C, ABCC2 c.1249G>A, ABCC 23972C>T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 1.84 L·h−1 and 275 L, respectively. Gender and UGT2B7 c.802T>C affected the clearance rate of MHD significantly. The established model was:CL/F=1.84×0.848UGT2B7×1.17GENDER. Where the genotype of UGT2B7 c.802T>C was CC, UGT2B7=0, otherwise UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.

Determination of 10-Hydroxyl Carbamazepine in Human Serum by High Performance Liquid Chromatography / 医药导报

Objective To establish a method for the determination of 10-hydroxyl carbamazepine (MHD),which is an activity metabolite of oxcarbazepine in human serum. Methods Serum samples were detected by high performance liquid chromatography (HPLC) after being processed by methanol protein deposition.The chromatographic column was Agilent TC-C18 (4.6 mm × 250 mm, 5 μm), with the mobile phase of acetonitrile-10 mmol ? L-1 KH2 PO4 ( 33 : 67) at a flow rate of 1.0 mL?min-1 .The detection wavelength was 230 nm,and phenacetin was used as an internal standard. Results The average recovery range of low,middle and high (1.0,10.0,60.0 μg?mL-1 ) concentrations for MHD was from 100.3％ to 106.0％.The RSD of intra-day and inter-day was ≤5.8％ (n= 5) and ≤7.4％ (n= 5),respectively.The limit detection of analysis method was 0.1 μg?mL-1 .Regression equation was Y = 0.1308X+ 0.0679 ( r = 0.9966,n = 5). Serum samples remained stable at room temperature,freezing and freeze thawing condition. Conclusion This method is sensitive,accurate,simple and quick,and can be used for monitoring the oxcarbazepine metabolites MHD in serum for clinical and pharmacokinetic study.

HLA DRB1*04:03 and Drug Reaction with Eosinophilia and Systemic Symptoms Induced by Oxcarbazepine: A Case Report / 대한소아신경학회지

Drug reaction with eosinophilia and systemic symptoms(DRESS), which occurs 2–8 weeks after taking a medication is a rare and potentially life-threatening drug-induced hypersensitivity reaction, which includes skin eruption, hematologic abnormalities, lymphadenopathy, and internal organ such as liver, lung, kidney involvement. Antiepileptic agents (e.g., carbamazepine, lamotrigine, phenytoin, and phenobarbital) and allopurinol are the most commonly reported causes. However, new antiepileptic agents, such as oxcarbazepine, rarely cause drug reaction with eosinophilia and systemic symptoms. A 11-year-old boy who was administered oxcarbazepine for 34 days developed widespread rashes, facial edema, fever, cough, nasal stuffiness, tonsillitis, and cervical lymphadenopathy. Laboratory test results showed leukocytosis, eosinophilia, thrombocytosis, elevated c-reactive protein, and elevated liver transaminase levels. As we suspected drug reaction with eosinophilia and systemic symptoms, we immediately withdrew oxcarbazepine and commenced corticosteroid therapy. The patient's skin lesions and abnormal laboratory results slowly improved. Before change the antiepileptic agents, we performed human leukocyte antigen (HLA) typing to assess the genetic risk factors of the drug reaction and the result was positive for HLA DRB1*04:03 known to cause severe acute drug hypersensitivity, such as Stevens-Johnson syndrome by oxcarbazepine in Koreans. We have presented the first report of drug reaction with eosinophilia and systemic symptoms associated with oxcarbazepine in a patient with HLA DRB1*04:03. Although DRESS by oxcarazepine is extremely rare and unpredictable, when suspected clinical symptoms occur, it is necessary to interrupt the causative drug rapidly and confirming the patient's HLA typing may help to select a safer alternative drug.

Hyponatremia by oxcarbacepin in multiple sclerosis, a case to take account / Hiponatremia por oxcarbacepina en esclerosis múltiple, un caso para tener en cuenta

Abstract Hyponatremia is one of the adverse effects in patients treated with oxcarbazepine. This can be seen masked by multiple symptoms which are simply attributable to other diseases, but we must always keep it in mind in a patient with a history of taking that medication. Many of patients are asymptomatic; Doses lower than 120 mmol/L show symptoms of severity which presented a patient with multiple sclerosis, which we will show below, so that diagnostic ability of clinicians plays a fundamental role. This is why the case is exposed in which a woman treated with oxcarbazepine for one of the clinical forms of multiple sclerosis, arrives at emergency departament with manifestations of this electrolytic disorder. For this reason, the clinical case served by the authors is chosen directly. It is concluded that this adverse reaction is not uncommon and that it must be taken into account in the differential diagnosis.

Resumen La hiponatremia es uno de los efectos adversos en los pacientes tratados con oxcarbazepina. Se puede ver enmascarada por múltiples síntomas, atribuibles a otras enfermedades, pero siempre debemos tenerla en mente en un paciente con antecedente de ingesta de dicho medicamento. Muchos de los pacientes son asintomáticos; cifras inferiores a 120 mmol/L ponen de manifiesto síntomas de severidad, como los presentados en el paciente con esclerosis múltiple que mostraremos a continuación. La habilidad diagnóstica del clínico, por tanto, juega un rol fundamental. Debido a esto, se expone un caso en el que una mujer tratada con oxcarbacepina, para una de las formas clínicas de esclerosis múltiple, llega a urgencias con manifestaciones de este trastorno electrolítico. Por esto se escoge el caso clínico atendido por los autores directamente. Se concluye que no es infrecuente esta reacción adversa y que hay que tenerla en cuenta a la hora de los diagnósticos diferenciales.

Data Analysis of Therapeutic Drug Monitoring for Three New Pediatric Antiepileptic Drugs / 中国药师

Objective:To analyze the situation of therapeutic drug monitoring ( TDM) for 3 new antiepileptic drugs including leve-tiracetam, lamotrigine and oxcarbazepine in our hospital to provide reference for the individualized drug treatment for the children with epilepsy. Methods:The basic information, dose and TDM data of levetiracetam, lamotrigine and oxcarbazepine of the children with ep-ilepsy during 2015 and 2016 were collected and statistically analyzed in our hospital. Results: Without obvious difference in mean dose, the average plasma concentrations of oxcarbazepine in 3-6-year-old,6-10-year-old and 10-18-year-old children were significantly higher than those in less than 3-year-old children(P<0. 05). The mean dose and the average plasma concentrations of lamotrigine in children at different ages had no statistical significance(P>0. 05). The average plasma concentration of levetiracetam in less than 3-year-old children was significantly higher than that in the other children (P<0. 05). The effective rate of clinical treatment within dif-ferent plasma concentration ranges had statistical significance(P<0. 05). Conclusion: There are inter-individual differences in the plasma concentrations of antiepileptic drugs among the children with epilepsy at different ages. So the plasma concentration of antiepi-leptic drugs should be monitored regularly in order to ensure the safety and effectiveness of medication for children.

Analysis of the Characteristics and Gene Relationship of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Induced by Oxcarbazepine / 中国药房

OBJECTIVE:To investigate the clinical characteristics and gene polymorphism of oxcarbazepine (OXC)- induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS:Retrieved from CNKI,Wanfang,VIP, PubMed,EMBase,SpringerLink and other databases,case reports about OXC-induced severe ADR were summarized and ana-lyzed. RESULTS:Twelve literatures were collected,and 13 case reports about OXC-induced SJS/TEN were obtained. Male had more OXC-induced severe skin ADR than female. ADR mostly occurred during 1-14 d after medication. All patients were cured with treatment of glucocorticoid and antiallergy,without death case. Genotyping for 8 patients were performed and 6 of them showed the presence of HLA-B*1502 allele. While HLA-B alleles of 2 patients were HLA-B*1518/B*4001,which was the variation of HLA-B*1502. CONCLUSIONS:OXC-induced ADR should be monitored closely. Great importance should be attached to patient education and follow-up program. HLA-B*1502 gene detection should be performed to guide rational use of OXC and optimize clini-cal drug use plan.

Study on the two-Year retention rates and long-term tolerability of Levetiracetam, Lamotrigine, and Oxcarbazepine in pediatric patients with epilepsy / 中国生化药物杂志

Objective To investigate the 2-year retention rates and tolerability of levetiracetam (LEV), Lamotrigine(LTG), and Oxcarbazepine(OXC) in pediatric patients with epilepsy.Methods 310 pediatric patients with epilepsy were included in this study: LEV (n=145), LTG (n=101), and OXC (n=64). The clinical efficacy, first discontinuation time and discontinuation reasons were recorded and compared. The retention rates at 12, 24, 52 and 104 weeks were evaluated. Results At the two-year follow up:Clinical efficacy didn't significantly differ among the three groups (P = 0.190); The 2-year retention rates for LEV, LTG, and OXC, were 68.28%, 72.28%, and 48.44%, respectively (P = 0.002). LEV and LTG had equivalent retention rates, whereas OXC retention was significantly inferior to the LEV and LTG retention (P<0.05). The common reasons for drug discontinuation were adverse effects (47.66%) and lack of efficacy (42.10%), while the rate of adverse effects leading to drug withdrawal of OXC (66.77%) was higher than that of LEV (36.96%, P = 0.003) and LTG (42.86%, P = 0.023). Conclusion These results suggested that LEV, LTG and OXC had similar clinical efficacy. LEV and LTG had comparable retention profiles and long-term tolerability in the 2-year treatment, while OXC therapy seemed to be relatively less useful. If there are no specific contradictions, pediatric patients with epilepsy could be better receiving LEV and LTG antiepileptic treatment.