Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy.

PURPOSE: The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. METHODS: We conducted a Nation-wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy-filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. RESULTS: Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. CONCLUSIONS: Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.

Effect of Carbamazepine on Darunavir Trough Concentrations: When the Dose Can Make the Difference-A Case Study.

BACKGROUND: Carbamazepine (CBZ) is an antiseizure medication known to induce the expression of cytochrome P4503A metabolic enzymes. Here, we describe a man living with HIV who underwent several changes in the daily dose of CBZ, which resulted in different induction effects on darunavir trough concentrations. METHODS: A 59-year-old man with HIV, successfully undergoing maintenance antiretroviral treatment with darunavir/cobicistat once daily (combined with raltegravir), was prescribed CBZ for recurrent trigeminal neuralgia. Over subsequent months, the patient underwent various changes in the doses (from 200 to 800 mg/d) and trough concentrations (from 3.6 to 18.0 mg/L) of CBZ, guided by clinical response to trigeminal neuralgia. RESULTS: A highly significant inverse association was observed between darunavir trough concentration and both CBZ dose or trough concentration (coefficient of determination >0.75, P < 0.0001). Ultimately, the darunavir dose was increased to 600 mg twice daily with ritonavir and dolutegravir to ensure optimal antiretroviral coverage, anticipating potential further uptitration of CBZ doses. CONCLUSIONS: The impact of CBZ on boosted darunavir exposure seemed to be dose- and concentration-dependent. The management of such drug-drug interactions in daily practice was facilitated through therapeutic drug monitoring. This case underscores the importance of a multidisciplinary approach that incorporates both antiretroviral and nonantiretroviral comedications contributing to the optimal management of polypharmacy in individuals living with HIV.

Trigeminal neuralgia.

Trigeminal neuralgia (TN) is a facial pain disorder characterized by intense and paroxysmal pain that profoundly affects quality of life and presents complex challenges in diagnosis and treatment. TN can be categorized as classical, secondary and idiopathic. Epidemiological studies show variable incidence rates and an increased prevalence in women and in the elderly, with familial cases suggesting genetic factors. The pathophysiology of TN is multifactorial and involves genetic predisposition, anatomical changes, and neurophysiological factors, leading to hyperexcitable neuronal states, central sensitization and widespread neural plasticity changes. Neurovascular compression of the trigeminal root, which undergoes major morphological changes, and focal demyelination of primary trigeminal afferents are key aetiological factors in TN. Structural and functional brain imaging studies in patients with TN demonstrated abnormalities in brain regions responsible for pain modulation and emotional processing of pain. Treatment of TN involves a multifaceted approach that considers patient-specific factors, including the type of TN, with initial pharmacotherapy followed by surgical options if necessary. First-line pharmacological treatments include carbamazepine and oxcarbazepine. Surgical interventions, including microvascular decompression and percutaneous neuroablative procedures, can be considered at an early stage if pharmacotherapy is not sufficient for pain control or has intolerable adverse effects or contraindications.

Porous-carbon/manganese composite catalyst transformed from waste biomass as peroxymonosulfate activator for carbamazepine degradation.

Activation of peroxymonosulfate (PMS) with solid catalysts for organic pharmaceutical degradation still faces challenge due to the demand of inexpensive catalysts. In this study, manganese-oxidizing microalgae (MOM) and its associated biogenic manganese oxides (BMO) were employed to prepare biomass-transformed porous-carbon/manganese (B-PC/Mn) catalyst through high-temperature calcination (850 °C). Remarkably, 100 % of carbamazepine (CBZ) was degraded within 30 min in the B-PC/Mn/PMS system. The degradation kinetic constant was 0.1718 min-1, which was 44.0 times higher than that of the biomass-transformed porous carbon mixed with MnOx activated PMS system. 1O2 was generated in the B-PC/Mn/PMS system, which is responsible for CBZ degradation. The MOM-BMO-associated structure greatly increased the specific surface areas and the contents of the C = O and pyrrolic-N groups, which facilitated PMS activation. The structure also induced the generation of Mn5C2, which exhibited a strong adsorption towards PMS. This study provides a novel strategy for preparing catalysts by using waste biomass.

Protecting against micropollutants in water storage tanks using in-situ TiO2 coated quartz optical fibers.

Photocatalyst-coated optical fibers (P-OFs) using UV-A LEDs offer a highly promising solution for the degradation of micropollutants within municipal, reuse, industrial or home distribution systems, by integrating P-OFs into water storage tanks. P-OFs have photocatalysts attached to bundles of optical fibers, enabling their direct deployment within tanks. This eliminates the necessity for photocatalyst slurries, which would require additional membrane or separation systems. However, a current limitation of P-OFs is light management, specifically light oversaturation of the coated photocatalysts and short light transmission distances along fibers. This study overcomes this limitation and reveals strategies to improve the light dissipation uniformity along P-OFs, and demonstrates the performance of P-OFs on degrading a model micropollutant, carbamazepine (CBZ). Key tunable variables of fibers and light emission conditions, including photocatalyst coating patchiness (p), minimum light incident angles (θm), radiant flux launched to fibers (Φi), and fiber diameters (D), were modeled to establish their relationships with the light dissipation uniformity in TiO2-coated quartz optical fibers (TiO2-QOFs). We then validated modeling insights by conducting experiments to examine how these variables influence the generation of evanescent waves which are localized energy on fiber surfaces, leading to either photocatalyst activation or the recapture of unused light back into fibers. We observed substantial enhancements in evanescent waves generation by decreasing p and increasing θm, resulting in uniform light dissipation which reduces light oversaturation and improves light transmission distances. Moreover, these optimizations led to a remarkable three-fold improvement in CBZ degradation rates and a 65% reduction in energy consumption. Such improvement substantially reduces the capital and operational cost and enhances practicality of energy-efficient photocatalysis without additional chemical oxidants for micropollutant degradation in water storage tanks.

Occurrence of pharmaceutically active compounds in groundwater and their effects to the human health.

Groundwater contamination by pharmaceutically active compounds (PhACs) has been considered a public health concern worldwide. Alongside the potential toxicological risk of these organic substances, many countries still rely on groundwater for drinking water supply. Thus, this study identified a priority list of seven licit PhACs, comprising acetaminophen (ACT), tramadol (TRA), carbamazepine (CBZ), erythromycin (ERY), sulfamethoxazole (SMX), metformin (MET), and oxazepam (OXZ). Consumption, concentration, and human toxicity in silico results were collected from open access databases. These three indicators were analyzed separately and grouped through a general risk index. The consumption index (data from the USA and Brazil) indicated that ACT, TRA, and MET are the most consumed. Monitoring samples from the USA and Europe (n = 816) indicated that OXZ and ERY stand out as the higher occurrence index considering both regions, but the ranking for each region showed considerable differences. When assessing toxicological risk, an index ≥ 0.5 was attributed to CBZ, MET, OXZ, SMX, and TRA. The general risk indicated the need to be attentive to MET, OXZ, and TRA as they presented ≥ 0.5 index values for at least two indicators.

Biological degradation of organic micropollutants in GAC filters-temporal development and spatial variations.

The capacity for organic micropollutant removal in granular activated carbon (GAC) filters for wastewater treatment changes over time. These changes are in general attributed to changes in adsorption, but may in some cases also be affected by biological degradation. Knowledge on the degradation of organic micropollutants, however, is scarce. In this work, the degradation of micropollutants in several full-scale GAC and sand filters was investigated through incubation experiments over a period of three years, using 14C-labeled organic micropollutants with different susceptibilities to biological degradation (ibuprofen, diclofenac, and carbamazepine), with parallel 16S rRNA gene sequencing. The results showed that the degradation of diclofenac and ibuprofen in GAC filters increased with increasing numbers of bed volumes when free oxygen was available in the filter, while variations over filter depth were limited. Despite relatively large differences in bacterial composition between filters, a degradation of diclofenac was consistently observed for the GAC filters that had been operated with high influent oxygen concentration (DO >8 mg/L). The results of this comprehensive experimental work provide an increased understanding of the interactions between microbial composition, filter material, and oxygen availability in the biological degradation of organic micropollutants in GAC filters.

Bio-electrochemical degradation of carbamazepine (CBZ): A comprehensive study on effectiveness, degradation pathway, and toxicological assessment.

Recent attention on the detrimental effects of pharmaceutically active compounds (PhACs) in natural water has spurred researchers to develop advanced wastewater treatment methods. Carbamazepine (CBZ), a widely recognized anticonvulsant, has often been a primary focus in numerous studies due to its prevalence and resistance to breaking down. This study aims to explore the effectiveness of a bio-electrochemical system in breaking down CBZ in polluted water and to assess the potential harmful effects of the treated wastewater. The results revealed bio-electro degradation process demonstrated a collaborative effect, achieving the highest CBZ degradation compared to electrodegradation and biodegradation techniques. Notably, a maximum CBZ degradation efficiency of 92.01% was attained using the bio-electrochemical system under specific conditions: Initial CBZ concentration of 60 mg/L, pH level at 7, 0.5% (v/v) inoculum dose, and an applied potential of 10 mV. The degradation pathway established by identifying intermediate products via High-Performance Liquid Chromatography-Mass Spectrometry, revealed the complete breakdown of CBZ without any toxic intermediates or end products. This finding was further validated through in vitro and in vivo toxicity assays, confirming the absence of harmful remnants after the degradation process.

Reactive layered hydroxide membrane for advanced water treatment: Micropollutant degradation and antifouling potential.

The effective removal of micropollutants by water treatment technologies remains a significant challenge. Herein, we develop a CoFe layered double hydroxide (CoFeLDH) catalytic membrane for peroxymonosulfate (PMS) activation to achieve efficient micropollutant removal with improved mass transfer rate and reaction kinetics. This study found that the CoFeLDH membrane/PMS system achieved an impressive above 98% degradation of the probe chemical ranitidine at 0.1 mM of PMS including five more micropollutants (Sulfamethoxazole, Ciprofloxacin, Carbamazepine, Acetaminophen and Bisphenol A) at satisfactory level (above 80%). Moreover, significant improvements in water flux and antifouling properties were observed, marking the membrane as a specific advancement in the removal of membrane fouling in water purification technology. The membrane demonstrated consistent degradation efficiency for several micropollutants and across a range of pH (4-9) as well as different anionic environments, thereby showing it suitability for scale-up application. The key role of reactive species such as SO4•-, and O2• - radicals in the degradation process was elucidated. This is followed by the confirmation of the occurrence of redox cycling between Co and Fe, and the presence of CoOH+ that promotes PMS activation. Over the ten cycles, the membrane could be operated with a flux recovery of up to 99.8% and maintained efficient performance over 24 h continuous operation. Finally, the efficiency in degrading micropollutants, coupled with reduced metal leaching, makes the CoFeLDH membrane as a promising technology for application in water treatment.

Preparation of Cobalt-Nitrogen Co-Doped Carbon Nanotubes for Activated Peroxymonosulfate Degradation of Carbamazepine.

Cobalt-nitrogen co-doped carbon nanotubes (Co3@NCNT-800) were synthesized via a facile and economical approach to investigate the efficient degradation of organic pollutants in aqueous environments. This material demonstrated high catalytic efficiency in the degradation of carbamazepine (CBZ) in the presence of peroxymonosulfate (PMS). The experimental data revealed that at a neutral pH of 7 and an initial CBZ concentration of 20 mg/L, the application of Co3@NCNT-800 at 0.2 g/L facilitated a degradation rate of 64.7% within 60 min. Mechanistic investigations indicated that the presence of pyridinic nitrogen and cobalt species enhanced the generation of reactive oxygen species. Radical scavenging assays and electron spin resonance spectroscopy confirmed that radical and nonradical pathways contributed to CBZ degradation, with the nonradical mechanism being predominant. This research presents the development of a novel PMS catalyst, synthesized through an efficient and stable method, which provides a cost-effective solution for the remediation of organic contaminants in water.

Enzymatic and non-enzymatic removal of organic micropollutants with spent mushroom substrate of Agaricus bisporus.

Water bodies are increasingly contaminated with a diversity of organic micropollutants (OMPs). This impacts the quality of ecosystems due to their recalcitrant nature. In this study, we assessed the removal of OMPs by spent mushroom substrate (SMS) of the white button mushroom (Agaricus bisporus) and by its aqueous tea extract. Removal of acesulfame K, antipyrine, bentazon, caffeine, carbamazepine, chloridazon, clofibric acid, and N, N-diethyl-meta-toluamide (DEET) by SMS and its tea was between 10 and 90% and 0-26%, respectively, in a 7-day period. Sorption to SMS particles was between 0 and 29%, which can thus not explain the removal difference between SMS and its tea, the latter lacking these particles. Carbamazepine was removed most efficiently by both SMS and its tea. Removal of OMPs (except caffeine) by SMS tea was not affected by heat treatment. By contrast, heat-treatment of SMS reduced OMP removal to < 10% except for carbamazepine with a removal of 90%. These results indicate that OMP removal by SMS and its tea is mediated by both enzymatic and non-enzymatic activities. The presence of copper, manganese, and iron (0.03, 0.88, and 0.33 µg L-1, respectively) as well as H2O2 (1.5 µM) in SMS tea indicated that the Fenton reaction represents (part of) the non-enzymatic activity. Indeed, the in vitro reconstituted Fenton reaction removed OMPs > 50% better than the teas. From these data it is concluded that spent mushroom substrate of the white button mushroom, which is widely available as a waste-stream, can be used to purify water from OMPs.

Exposure to environmental pharmaceuticals affects the macromolecular composition of mussels digestive glands.

Human pharmaceuticals represent a major challenge in natural environment. A better knowledge on their mechanisms of action and adverse effects on cellular pathways is fundamental to predict long-term consequences for marine wildlife. The FTIRI Imaging (FTIRI) spectroscopy represents a vibrational technique allowing to map specific areas of non-homogeneous biological samples, providing a unique biochemical and ultrastructural fingerprint of the tissue. In this study, FTIRI technique has been applied, for the first time, to characterize (i) the chemical building blocks of digestive glands of Mytilus galloprovincialis, (ii) alterations and (iii) resilience of macromolecular composition, after a 14-days exposure to 0.5 µg/L of carbamazepine (CBZ), valsartan (VAL) and their mixture, followed by a 14-days recovery period. Spectral features of mussels digestive glands provided insights on composition and topographical distribution of main groups of biological macromolecules, such as proteins, lipids, and glycosylated compounds. Pharmaceuticals caused an increase in the total amount of protein and a significant decrease of lipids levels. Changes in macromolecular features reflected the modulation of specific molecular and biochemical pathways thus supporting our knowledge on mechanisms of action of such emerging pollutants. Overall, the applied approach could represent an added value within integrated strategies for the effects-based evaluation of environmental contaminants.

Compared to oxcarbazepine and carbamazepine, botulinum toxin type A is a useful therapeutic option for trigeminal neuralgia symptoms: A systematic review.

OBJECTIVES: This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). MATERIAL AND METHODS: We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023. RESULTS: We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent. CONCLUSIONS: Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.

Effect of zeolites on the reduction of the ecotoxicity of carbamazepine in the environment.

In this study, the impact of calcination of zeolites on the ecotoxicity of carbamazepine solutions in two matrices, water and synthetic sewage, was assessed. Two types of zeolites were tested: natural zeolite, in the form of a zeolite rock consisting mainly of clinoptilolite, and a synthetic zeolite type 5 A. Additionally, zeolites were calcined at a temperature of 200 °C. The kinetics of carbamazepine adsorption in aqueous solutions and in synthetic sewage matrix was determined. Higher adsorption capacity was obtained for carbamazepine aqueous solutions as well as zeolites after the calcination process. Considering type of zeolite, the highest and fastest uptake of carbamazepine was observed for natural zeolite after calcination. In the case of ecotoxicity, carbamazepine solutions before adsorption was the most toxic towards Raphidocelis subcapitata, next Aliivibrio fischeri and Daphnia magna, regardless to the matrix type. The differentiation in toxicity regarding the type of matrix was observed, in the case of algae and bacteria, higher toxicity was demonstrated by carbamazepine solutions in the water matrix, while in the case of crustaceans-the sewage matrix. After the adsorption process, the toxicity of carbamazepine solutions on zeolites decreased by 34.5-60.9 % for R. subcapitata, 33-39 % for A. fischeri and 55-60 % for D. magna, thus confirming the effectiveness of the proposed method of carbamazepine immobilization.

Pharmacological evaluation of E2730, a novel selective uncompetitive GAT1 inhibitor, on epileptiform activities in resected brain tissues from human focal cortical dysplasia ex vivo.

Focal cortical dysplasia (FCD) is an important etiology of focal epilepsy in children and adults. However, only a few preclinical models sufficiently reproduce the characteristic histopathologic features of FCD. To improve the success rate of clinical trials for antiseizure medications (ASMs) in patients with FCD, more human-relevant preclinical models are needed, and epileptic foci resected from patients are a powerful tool for this purpose. Here, we conducted ex vivo studies using epileptic foci resected from patients with FCD type II to evaluate the pharmacologic effects of the ASM candidate E2730, a selective uncompetitive inhibitor of γ-aminobutyric acid transporter 1. We used the same ex vivo assay system to assess carbamazepine (CBZ), an ASM often prescribed for focal epilepsy, as a reference. At the higher dose tested (200 µM), both E2730 and CBZ suppressed spontaneous epileptiform activities almost completely. At the lower dose (100 µM), CBZ reduced the area of brain tissue showing epileptiform activity, whereas E2730 significantly decreased the number of epileptiforms. These findings suggest that E2730-both as a single agent and in combination with CBZ-merits evaluation in clinical trials involving patients with FCD.

Insight into the generation of toxic by-products during UV/H2O2 degradation of carbamazepine: Mechanisms, N-transformation and toxicity.

Carbamazepine (CBZ) is a widely used anticonvulsant drug that has been detected in aquatic environments. This study investigated the toxicity of its by-products (CBZ-BPs), which may surpass CBZ. Unlike the previous studies, this study offered a more systematic approach to identifying toxic BPs and inferring degradation pathways. Furthermore, quadrupole time-of-flight (QTOF) and density functional theory (DFT) calculations were employed to analyze CBZ-BP structures and degradation pathways. Evaluation of total organic carbon (TOC) and total nitrogen (TN) mineralization rates, revealed carbon (C) greater susceptibility to mineralization compared with nitrogen (N). Furthermore, three rules were established for CBZ decarbonization and N removal during degradation, observing the transformation of aromatic compounds into aliphatic hydrocarbons and stable N-containing organic matter over time. Five potentially highly toxic BPs were screened from 14 identified BPs, with toxicity predictions guiding the selection of commercial standards for quantification and true toxicity testing. Additionally, BP207 emerged as the most toxic, supported by the predictive toxicity accumulation model (PTAM). Notably, highly toxic BPs feature an acridine structure, indicating its significant contribution to toxicity. These findings offered valuable insights into the degradation mechanisms of emerging contaminants and the biosafety of aquatic environments during deep oxidation.

Molecular, behavioral, and growth responses of juvenile yellow catfish (Tachysurus fulvidraco) exposed to carbamazepine.

Carbamazepine (CBZ) is an anticonvulsant medication used to treat epilepsy and bipolar disorder. Due to its persistence and low removal rate in wastewater treatment plants, it is frequently detected in the environment, raising concerns regarding its potential adverse effects on aquatic organisms and ecosystems. In this study, we aimed to assess the impact of CBZ on the behavior and growth of juvenile yellow catfish Tachysurus fulvidraco, a native and economically important species in China. Fish were exposed to CBZ at three concentrations of 1, 10, or 100 µg/L for 14 days. The fish exposed to 10 and 100 µg/L of CBZ exhibited decreased feeding, and a significant increase in cannibalistic tendencies was observed in fish exposed to 100 µg/L CBZ. Acetylcholinesterase activity was increased in the brain of fish exposed to 100 µg/L CBZ. CBZ also inhibited the growth of yellow catfish. To better elucidate mechanisms of toxicity, transcriptomics was conducted in both the brain and liver. In the brain, gene networks associated with neurotransmitter dysfunction were altered by CBZ, as well as networks associated with mitochondrial dysfunction and metabolism. In the liver, gene networks associated with the immune system were altered by CBZ. The current study improves comprehension of the sub-lethal effects of CBZ and reveals novel insight into molecular and biochemical pathways disrupted by CBZ, identifying putative key events associated with reduced growth and altered behavior. This study emphasizes the necessity for improved comprehension of the effects of pharmaceutical contaminants on fish at environmentally relevant levels.

Second antiseizure medication monotherapy in patients with adult-onset epilepsy: A register-based analysis.

OBJECTIVE: Revision of therapy is fundamental in epilepsy care, since only half of patients achieve seizure freedom and tolerate the first antiseizure medication (ASM). We studied the selection and retention of second antiseizure medication monotherapy in adults who discontinued treatment with one of the three most frequently prescribed first ASMs, and the impact of age or brain comorbidities. METHODS: Using Swedish national registers, we conducted a population-based, retrospective cohort study from 2007 to 2019 on patients age ≥ 30 at the epilepsy diagnosis that had switched to a second monotherapy after the three most common initial monotherapies (n = 7369). Retention rates (RR) were estimated via Kaplan-Meier. Discontinuation of the second monotherapy was defined as 12-month prescription gap or initiation of a third ASM. Analyses were stratified by sex, age, and presence of stroke or dementia. RESULTS: The three most commonly prescribed second ASMs were carbamazepine, levetiracetam, and lamotrigine. The 1-year retention rate was 63-76% in all patients. For groups with stroke or dementia, the maximal 1-year RRs were 77% and 87%, respectively. After five years, retention rates ranged from 12% to 39%. There were no major differences between ASMs, apart from in patients discontinuing carbamazepine, where lamotrigine had a superior retention compared to levetiracetam as second monotherapy. SIGNIFICANCE: The three most often prescribed second ASMs seem to be suitable treatment options according to present guidelines. The second ASMs' retention rates were initially high in all studied patient groups but dropped to approximately the expected proportion of second monotherapy responders over the next five years. This suggests that therapy revision could be expedited.

Cost-effectiveness analysis of HLA-B*15:02 screening before treatment of epilepsy in Indonesia.

INTRODUCTION: Adverse skin reactions due to drugs such as Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) occur in 3% of people receiving anti epileptic drugs (AED). Although SJS/TEN has a low incidence, the mortality and morbidity rates are high. Indonesia has not adopted HLA-B*1502 screening prior to administration of carbamazepine (CBZ), although previous studies found a relationship between HLA-B*1502 and SJS/TEN. METHODS: A hybrid decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed focal epilepsy: CBZ direct therapy, levetiracetam (LEV) direct therapy, and therapy based on HLA-B*15:02 test results. From a societal perspective, base case and sensitivity analyses were carried out over a lifetime. RESULTS: Direct administration of CBZ appears to have a slightly lower average cost than the HLA-B*15:02 allele screening strategy. The increase in quality-adjusted life year (QALY) in HLA-B*15:02 screening before treatment related to the cost difference reached 0.519 with an incremental cost-effectiveness ratio (ICER) of around USD 984 per unit of QALY acquisition. Direct treatment of LEV increased treatment costs by almost USD 2000 on average compared to the standard CBZ strategy. The increase in QALY is 0.834 in direct levetiracetam treatment, with an ICER of around USD 2230 for each QALY processing. CONCLUSION: Calculation of the cost-effectiveness of lifetime epilepsy therapy in this study found that the initial screening strategy with the HLA-B*15:02 test was the most cost-effective.