Prescription trends in anti-seizure medications for adult patients with epilepsy in Japan: A retrospective cohort study using the database of health insurance claims between 2015 and 2019

Jin, Kazutaka; Obara, Taku; Hirano, Kyoko; Hirai, Daichi; Kiuchi, Masatoshi; Tanaka, Takeshi; Nakasato, Nobukazu

doi:10.1016/j.yebeh.2022.108841

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…Phenytoin has a narrow therapeutic concentration window and is still widely used worldwide for the treatment of epilepsy, with a market share of 9% in the US 131 and 5% in Japan. 132 Genetically determined CYP2C9 poor and intermediate metabolizer phenotypes are listed by the US Food and Drug Administration (FDA) as clinically relevant polymorphisms for treatment with phenytoin, 133 while the FDA drug label advises caution for CYP2C19 and CYP2C9 poor and intermediate metabolizers. 134 However, there is limited information on the magnitude of plasma concentration increases in the different CYP phenotypes, on guidelines for the dose optimization of CYP2C9 and CYP2C19 intermediate and poor metabolizers, and on the utility of preemptive CYP2C9 and CYP2C19 genotyping.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs

Milosavljević,

Manojlović,

Matković

et al. 2024

JAMA Netw Open

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ImportancePrecise estimation of a patient’s drug metabolism capacity is important for antiseizure dose personalization.ObjectiveTo quantify the differences in plasma concentrations for antiseizure drugs associated with variants of genes encoding drug metabolizing enzymes.Data SourcesPubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to September 30, 2023, without language restrictions.Study SelectionTwo reviewers performed independent study screening and assessed the following inclusion criteria: appropriate genotyping was performed, genotype-based categorization into subgroups was possible, and each subgroup contained at least 3 participants.Data Extraction and SynthesisThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for data extraction and subsequent quality, validity, and risk-of-bias assessments. The results from the included studies were pooled with random-effect meta-analysis.Main Outcomes and MeasuresPlasma concentrations of antiseizure drugs were quantified with the dose-normalized area under the concentration-time curve, the dose-normalized steady state concentration, or the concentrations after a single dose at standardized dose and sampling time. The ratio of the means was calculated by dividing the mean drug plasma concentrations of carriers and noncarriers of the pharmacogenetic variant.ResultsData from 98 studies involving 12 543 adult participants treated with phenytoin, valproate, lamotrigine, or carbamazepine were analyzed. Studies were mainly conducted within East Asian (69 studies) or White or European (15 studies) cohorts. Significant increases of plasma concentrations compared with the reference subgroup were observed for phenytoin, by 46% (95% CI, 33%-61%) in CYP2C9 intermediate metabolizers, 20% (95% CI, 17%-30%) in CYP2C19 intermediate metabolizers, and 39% (95% CI, 24%-56%) in CYP2C19 poor metabolizers; for valproate, by 12% (95% CI, 4%-20%) in CYP2C9 intermediate metabolizers, 12% (95% CI, 2%-24%) in CYP2C19 intermediate metabolizers, and 20% (95% CI, 2%-41%) in CYP2C19 poor metabolizers; and for carbamazepine, by 12% (95% CI, 3%-22%) in CYP3A5 poor metabolizers.Conclusions and RelevanceThis systematic review and meta-analysis found that CYP2C9 and CYP2C19 genotypes encoding low enzymatic capacity were associated with a clinically relevant increase in phenytoin plasma concentrations, several pharmacogenetic variants were associated with statistically significant but only marginally clinically relevant changes in valproate and carbamazepine plasma concentrations, and numerous pharmacogenetic variants were not associated with statistically significant differences in plasma concentrations of antiseizure drugs.

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Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs

Milosavljević,

Manojlović,

Matković

et al. 2024

JAMA Netw Open

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“… Changes in prescribing patterns over time for antiseizure medications in different countries followed by the time period evaluated: United Kingdom (UK: 2003-2016), Japan (2015-2018), China (2013-2018), United States (US: 2012-2019) and Germany (2008-2020). (Figure adapted from 31 54 55 56 57 58 :). …”

Section: Prescription Patterns and Challengesmentioning

confidence: 99%

Practices in the prescription of antiseizure medications: is it time to change?

Pinto,

Silva,

João

et al. 2024

Arq Neuropsiquiatr

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The treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.

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“…In a 2018 Japanese retrospective cohort study, VPA was the most widely prescribed older (approved before 1990) ASM (43.3%), whereas ZNS made up only 9.2% of total older ASM prescriptions. 42 Newer ASMs saw an upward trend in prescribing rates from 2015 to 2018, possibly due to perceived fewer AEs and drug interactions compared with older ASMs, although newer ASMs may not offer better overall seizure control. A review of common concerns from providers on the AEs and conceived limitations of ZNS follows.…”

Section: Safety Considerations/adverse Effectsmentioning

confidence: 99%

Zonisamide

Gidal,

Resnick,

Smith

et al. 2024

Neur Clin Pract

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Purpose of ReviewZonisamide (ZNS) was first approved in the United States in 2000 for the adjunctive treatment of patients aged 16 years or older with partial (focal) seizures. Although ZNS has been proven to treat multiple seizure types, it has been largely underutilized in US clinical practice.Recent FindingsPublished literature demonstrated that antiseizure medications (ASMs) acting on Na+and Ca2+channels may add beneficial effects in many seizure types by reducing seizure frequency and leading to overall improvements. In addition, effects of ZNS may lead to clinical improvements in Parkinson disease, alcohol and sleep disorders, pain, and migraine. ZNS is available in multiple formulations and is a safe and effective, broad spectrum ASM.SummaryThe purpose of this review was to provide an update to what is known about the efficacy of ZNS and where it shows benefits in the treatment of patients with epilepsy and other CNS disorders through its many unique mechanisms of action.

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Prescription trends in anti-seizure medications for adult patients with epilepsy in Japan: A retrospective cohort study using the database of health insurance claims between 2015 and 2019

Cited by 6 publications

References 29 publications

Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs

Pharmacogenetic Variants and Plasma Concentrations of Antiseizure Drugs

Practices in the prescription of antiseizure medications: is it time to change?

Zonisamide

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