• 한국임상약학회지
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• 제17권1호
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• pp.46-51
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• 2007

This study was aimed to provide the controlled terminology for adverse drug reactions by selecting an appropriate internationally standardized classifications (WHO-ART or MedDRA). We collected the relevant information on ADR terminology systems including WHO-ART and MedDRA by online searching and visiting pharmaceutical companies and WHO UMC (Uppsala Monitoring Centre, Uppsala, Sweden). For MedDRA, project leader directly communicated with the officer of MSSO (Maintenance and Support Services Organization). Collecting all the pertinent information, two possible terminology classifications or systems (WHO-ART and MedDRA) were compared in the views of acceptability, cost-effectiveness and international feasibility and reviewed by the consultation committee and finally WHO-ART was selected.

• 한국임상약학회지
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• 제27권3호
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• pp.143-149
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• 2017

Background: L-asparaginase (L-ASP) is a critical agent for the treatment of acute lymphoblastic leukemia and lymphoma, which is associated with serious toxicities including hypersensitivity, pancreatitis and thrombosis. Methods: To evaluate the toxicity of L-ASP in real clinical settings, we included the patients with L-ASP adverse drug reactions (ADRs) reported in a regional pharmacovigilance center of Seoul St. Mary's hospital from January 2014 to December 2015. Results: A total of 83 cases of L-ASP related ADRs were reported in 54 patients. Of these 83 cases, 65 cases (78.3%, 65/83) were spontaneously reported and 18 cases (21.7%, 18/83) were detected by further medical records review. Of the patients with ADRs, pediatric patients accounted for 83.3% of the cases (45/54) and median age was 9 years. The most common clinical manifestations of ADRs were hematology manifestations (31.3%, 26/83), followed by hepatobiliary manifestations (18.1%, 15/83). Thirty-four serious ADRs were reported in 19 patients. The sserious ADR group showed significantly longer hospitalization and higher rate of discontinuation of L-ASP than the non-serious ADR group (p = 0.005, 0.03). The most common clinical manifestations of serious ADRs were hepatobiliary manifestations (41.2%, 14/34). In total, 8 cases (9.6%, 8/83) of unlabeled ADRs were identified. They were serious ADRs. Conclusion: We identified unlabeled serious ADRs of L-ASP. Also, correlations were observed between serious ADRs and length of hospitalization, discontinuation rate respectively. Further investigations and developed spontaneous ADR reporting systems are needed to evaluate these correlations.

• 한국임상약학회지
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• 제24권1호
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• pp.39-44
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• 2014

Purpose: To investigate adverse drug reactions (ADR) and causative drugs in the elderly 65 years of age or older, using Korean spontaneous reporting adverse events reporting database from June 2009 to December 2010. Methods: We estimated the association between ADRs and implicated medications by calculating a proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). We reexamined the most frequently implicated medications and ADRs, and the seriousness of ADRs. Then, we assessed reports and concordant rate of ADRs due to medications designated as "high-risk" in elderly by 2012 healthcare effectiveness data and information set (HEDIS) or "potentially inappropriate" by 2012 American Geriatrics Society updated Beers criteria for potentially inappropriate medications (PIMs). Results: Among 15,484 elderly reports, data-mining analysis by PRR, ROR and IC showed that 421 drug-ADR pairs were detected as signals (3,189). The most frequently reported ADR and causative drug were urticaria (470) and contrast media agents (647), respectively. One hundred eighty nine ADR cases were graded as serious. Twenty-two kinds of high-risk medications were shown to be implicated in only 0.9% of ADRs. Only thirty-nine cases were consistent with 2012 Beers criteria or HEDIS. Conclusion: These results suggest that management of the other medications including contrast media agents as well as close monitoring of PIMs are necessary for reducing ADRs in the elderly.

• Toxicological Research
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• 제35권4호
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• pp.319-330
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• 2019

Adverse drug reactions (ADRs) constitute key factors in determining successful medication therapy in clinical situations. Integrative analysis of electronic medical record (EMR) data and use of proper analytical tools are requisite to conduct retrospective surveillance of clinical decisions on medications. Thus, we suggest that electronic medical recording and human genetic databases are considered together in future directions of pharmacovigilance. We analyzed EMR-based ADR studies indexed on PubMed during the period from 2005 to 2017 and retrospectively acquired 1161 (29.6%) articles describing drug-induced adverse reactions (e.g., liver, kidney, nervous system, immune system, and inflammatory responses). Of them, only 102 (8.79%) articles contained useful information to detect or predict ADRs in the context of clinical medication alerts. Since insufficiency of EMR datasets and their improper analyses may provide false warnings on clinical decision, efforts should be made to overcome possible problems on data-mining, analysis, statistics, and standardization. Thus, we address the characteristics and limitations on retrospective EMR database studies in hospital settings. Since gene expression and genetic variations among individuals impact ADRs, pharmacokinetics, and pharmacodynamics, appropriate paths for pharmacovigilance may be optimized using suitable databases available in public domain (e.g., genome-wide association studies (GWAS), non-coding RNAs, microRNAs, proteomics, and genetic variations), novel targets, and biomarkers. These efforts with new validated biomarker analyses would be of help to repurpose clinical and translational research infrastructure and ultimately future personalized therapy considering ADRs.

• Tuberculosis and Respiratory Diseases
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• 제67권4호
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• pp.325-330
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• 2009

Background: Pulmonary tuberculosis (TB) is still common disease among the elderly patients in Korea where the overall incidence of TB is decreasing. Adverse drug reactions (ADR) associated with anti-TB drugs occurs frequently. Especially the aged tends to have more frequent ADRs than younger ones. These ADRs can cause significant morbidity, compromise therapeutic effects of drugs and even induce drug resistance. Therefore we evaluated the effect of ADRs on the first-line anti-TB drugs in elderly patients with active pulmonary TB. Methods: We retrospectively reviewed the charts and radiological findings of the patients with 65 and older who were bacteriologically confirmed as active TB and treated with standard anti-TB drugs for at least 6 months. Major ADR was defined with temporary or continuous stop of any first-line drugs intake. Results: An ADR was noted in 54% of all patients. The incidence of major ADR was 32% in all elderly patients. Dermatologic ADR (9%) was the most common among the major ADRs. GI trouble (8%), arthralgia (6%), visual change (6%), hepatotoxicity (4%), and fever (1%) were also noted. The drugs responsible for major ADR were ethambutol (62%), pyrazinamide (35%), rifampin (18%) and isoniazid (9%). Major ADRs were associated with higher ESR level at the initiation of anti-TB drugs. Conclusion: First-line anti-TB drugs in elderly patients frequently caused the major ADRs. Therefore the elderly patients receiving anti-TB drugs should be closely monitored and better tolerable therapy should be considered as part of a TB research agenda.

• 정신신체의학
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• 제30권2호
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• pp.66-72
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• 2022

클로자핀은 치료 저항성 조현병 약물치료의 "최적 표준(gold standard)"으로 받아들여지고 있다. 클로자핀은 다른 항정신병약물에서 흔히 나타나는 추체외로 증후군, 지연이상 운동증을 거의 일으키지 않고 고프로락틴의 일시적인 상승만 보이는 한편, 발열 등의 약물 이상반응이 흔하게 나타난다. 치료 시작 시기에 드물게 무과립구증, 신경이완제 악성증후군과 같은 치명적인 부작용과 연관된 발열이 발생할 수 있으며, 이 경우 클로자핀을 즉시 중단해야 한다. 그러나 발열의 양성 원인은 생명을 위협하는 부작용보다 훨씬 빈번하므로 치료 시작 시기에 발열을 보이는 경우 무조건 클로자핀을 중단하는 것은 타당하지 않다. 또한, 치료 유지 시기에도 언제든지 발열은 발생할 수 있다. 특히 폐렴의 위험은 시간이 지남에 따라 감소하지 않으며, 클로자핀은 다른 항정신병약물 보다 폐렴의 위험이 높으므로 항상 이를 염두에 두고 치료제 모니터링을 통하여 약물 용량을 결정하는것이 권장된다.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2023년도 춘계학술발표대회
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• pp.670-672
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• 2023

본 논문에서는 소셜 미디어 약물 리뷰 데이터로부터 약물 이상 반응을 탐지하는 모델인 FC-BERT 를 기반으로 소셜 네트워크 분석을 활용하여 웹 애플리케이션을 구현하였다. FC-BERT 모델을 거쳐 나온 개체명 인식 결과 중에 같은 의미를 가진 서로 다른 약물 이상 반응 표현들을 MedDRA 부작용 사전을 참고하여 하나의 MedDRA 용어로 표준화하여 매핑했다. 해당 결과에 소셜 네트워크 분석 기법을 적용하여 생성한 상위 15 개의 ADR 동시 출현 그래프를 상위 30 개의 워드 클라우드와 함께 시각화하여 보여주는 웹 애플리케이션을 개발했다. 동시 출현 그래프는 가장 많은 리뷰에서 동시에 나타나는 ADR 쌍을 보여준다. 본 논문에서 제안한 웹 애플리케이션은 사람마다 다르게 나타나는 다양한 약물 이상 반응을 사용자에게 좀 더 접근성이 좋게 제공할 수 있을 것으로 보인다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• 한국임상약학회지
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• 제22권4호
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• pp.340-346
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• 2012

Background: Amphotericin B is a mainstay in the treatment of many systemic fungal infections due to its wide antifungal spectrum and low incidence of resistance. However, the use of amphotericin B is limited by its nephrotoxicity. Objectives: The objective of this study was to evaluate the incidence and risk factors of renal adverse drug reactions (ADRs) of conventional amphotericin B (Fungizone$^{(R)}$). In addition, we compared the changes of serum creatinine (SCr) between patients who remained conventional amphotericin B and patients who were switched to liposomal amphotericin B after occurrence of renal adverse reactions. Methods: Adult hospitalized patients who reported renal adverse reactions caused by conventional amphotericin B from January 2011 to July 2012 at pharmacovigilance center in Yonsei University Healthcare System included in this study. ADRs scored as 'doubtful' in Naranjo probability ADR scale were excluded. We retrospectively analyzed patients' basic clinical characteristics, concurrent diseases or nephrotoxic drugs in order to find variables that can correlate with occurrence of renal ADRs. Changes in SCr were compared between conventional amphotericin B group and liposomal amphotericin B group. Results: A total of 231 ADRs after administration of conventional amphotericin B in 75 patients were reported to pharmacovigilance center and assessed their severities as 'possible', 'probable', or 'definite'. Renal adverse reaction was the most common ADR with incidence rate of 42% (96 of 231 ADRs). Mean change in SCr from baseline was 0.26 mg/dL (change % 37.8) and statistically significant (p=0.000). Simple correlations analysis revealed that the number of concurrent diseases and number of nephrotoxic drugs were positively correlated with changes in SCr, but these results were not statistically significant. Among 43 patients who remained amphotericin B after occurrence of renal ADRs, 27 patients was administered conventional amphotericin B and 16 patients changed to liposomal amphotericin B. Mean change in SCr in amphotericin B group was 0.23 mg/dL (32.75%), whereas mean change in SCr in liposomal amphotericin B group were -0.28 mg/dL (19.38%) and difference between two groups was statistically significant (p=0.003). The numbers of patient with SCr elevation more than 30% were 9 (33.3%) in amphotericin B group and 2 (12.5%) in liposomal amphotericin B group (Odd Ratio=3.50, 95% Confidence Interval 0.65-18.85; p=0.130). Conclusion: An analysis of ADRs due to amphotericin B administration revealed significant mean changes in SCr from baseline. Switching to liposomal amphotericin B showed significant decrease in SCr compared with conventional amphotericin B.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2022년도 춘계학술발표대회
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• pp.549-552
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• 2022

최근 소셜미디어 리뷰 데이터를 활용한 약물 이상 반응 탐지 연구가 활발히 진행되고 있지만, 약물을 복용하기 전 증상과 약물 이상 반응을 구분하지 못한다는 한계가 있다. 본 논문에서는 약물 이상 반응 탐지에서 약물 복용 전의 증상을 구분할 수 있는 Filtering Clinical BERT(FC-BERT) 모델을 제안하였다. FC-BERT 는 약물 복용 전 증상과 다른 약물에 대한 부작용 표현을 제거하기 위해 약물명이 나오기 전 모든 문장을 제거하는 필터링과 약물-부작용 쌍을 추출하는 모델을 사용했다. 성능 평가 실험을 위해 문장에 대한 ADE(Adverse Drug Event) 여부가 들어있는 ADE Corpus V2 데이터를 활용하였고 SPARK NLP 라이브러리에서 제공하는 ADE Pipeline 모델과 비교하여 성능 평가를 실시하였다. 실험 결과 필터링을 활용한 FC-BERT 모델이 기존 모델보다 정확도, 평균 정밀도, 평균 재현율, 평균 F1-score 가 모두 높은 결과를 보여주었다. 본 논문에서 제시한 모델은 기존 연구의 한계점을 보완하여 보다 정확한 약물 부작용 시그널을 탐지하는데 기여할 수 있을 것이다.