• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.226-237
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• 2022

Background: Monoclonal antibodies for the treatment of patients with different types of cancer, such as cetuximab, have been widely used for the past 10 years in oncology. Although drug information package insert contains some representative adverse events which were observed in the clinical trials for drug approval, the overall adverse event patterns on the real-world cetuximab use were less investigated. Also, there have been no published papers that deal with the full spectrums of adverse drug events of cetuximab using national-wide drug safety surveillance systems. Methods: In this study, we detected new adverse event signals of cetuximab in the Korea Adverse Event Reporting System (KAERS) by utilizing proportional reporting ratios, reporting odds ratios, and information components indices. Results: The KAERS database included 869,819 spontaneous adverse event reports, among which 2,116 reports contained cetuximab. We compared the labels of cetuximab among the United States, European Union, Australia, Japan, and Korea to compare the current labeling information and newly detected signals of our study. Some of the signals including hyperkeratosis, tenesmus, folliculitis, esophagitis, neuralgia, disseminated intravascular coagulopathy, and skin/throat tightness were not labeled in the five countries. Conclusion: We identified new signals that were not known at the time of market approval.

• The Korean Journal of Applied Statistics
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• v.27 no.1
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• pp.1-11
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• 2014

The Weighted Logrank test and its special case, Logrank test are widely used to compare survival distributions; however, these methods are inappropriate when the sample size is small or censoring distributions are not equal since they use test statistics from approximate distributions. A permutation test can be an alternative for small sample cases; however, this should be used only when censoring distributions are equal. To handle cases with small sample size and unequal censoring distributions, the permutation-imputation method was developed to compare two survival distributions. In this paper, approximate method, permutation method and permutation-imputation method were compared using a Logrank test and Prentice-Wilcoxon test for three or more survival distributions comparison.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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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.

• Korean Journal of Clinical Pharmacy
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• v.31 no.1
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• pp.53-60
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• 2021

Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion: All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission. Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

• Korean Journal of Clinical Pharmacy
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• v.32 no.3
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• pp.204-214
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• 2022

Objective: This study aimed to investigate the occurrence and types of the adverse events (AEs) associated with oral fluconazole and itraconazole and factors associated with specific types of AEs. Methods: We analyzed AEs reported by community pharmacies nationwide over 10 years using the Korea Adverse Event Reporting System database. Various AE terms were categorized into 18 types, and concomitant medications were classified by drug-drug interaction (DDI) severity. The relationship between the specific type of AE and age, sex, and number of concomitant medications was investigated using multiple logistic regression analysis. Results: A total of 879 AE reports of fluconazole and 401 reports of itraconazole were analyzed; of these reports, 321 and 83 reports of fluconazole and itraconazole, respectively, described concomitant drug administration categorized as DDI severity of contraindicated or major. Women had a higher risk of psychiatric AEs associated with fluconazole use (OR, 1.587; p=0.042). Polypharmacy increased the risk for psychiatric AEs (OR, 3.598; p<0.001 for fluconazole and OR, 2.308; p=0.046 for itraconazole). In dermatologic AEs, the mean age of patients who received itraconazole was lower than that of patients who received fluconazole (46.3±16.8 vs. 54.9±15.4; p<0.001). Co-administration of fluconazole with 1-3 drugs increased the risk of neurological AEs (OR, 1.764; p=0.028). Conclusion: When using fluconazole and itraconazole, psychiatric AEs should be noted, particularly in women and in case of polypharmacy; moreover, when fluconazole is co-administered with other drugs, attention should be paid to the occurrence of neurological AEs.

• The Journal of Korean Medicine
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• v.45 no.1
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• pp.165-181
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• 2024

Objectives: This study was aimed to review the global status of adverse event (AE) reports and the characteristics of the reported AEs of plants managed as herbal medicines (HMs) with toxic precautions in Korea. Methods: This is a cross-sectional quantitative study that analyzed information available through VigiAccess, a website that provides summarized statistical information from the WHO's global AE database to the public. VigiAccess was searched in 8 Jan, 2024. Information on the total number of reports, number of reports by year and continent, and the age and gender of patients were obtained, and the types of frequently reported AEs were also reviewed. Results: Data on the status of report submissions were obtained for a total of 9 HMs including Aconitum ciliare, Aconitum carmichaeli, Arisaema japonicum, Pinellia ternata, Euphorbiae Lathyridis, Croton tiglium, Strychni Ignatii, Strychnons nux-vomica, and Linum usitatissimum. The number of reports per HM was from 1 to 137. The most commonly reported type of AEs were gastrointestinal disorders in most of the HMs, followed by neurological disorders. Serious adverse events were reported only in Strychni Ignatii, Strychnons nux-vomica, and Linum usitatissimum, including one case of death. Conclusions: This study shows the status of reported AEs of botanicals considered as HMs with toxic precautions in Korea based on real world data. However, when interpreting the findings of this study, readers should consider the significant limitations of this study mainly because of the characteristics of the data source.