항히스타민제 이상반응

강혜련,안경민,김현지 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.1

Histamine is one of the most essential biochemical molecules involved in various responses, including inflammation, neurotransmission, and cell proliferation, in diverse organs. Clinical manifestations of allergic diseases are often triggered or initiated by histamine. In order to prevent histamine reactions in allergic disease, clinicians have attempted to develop antagonist of histamine receptors. Due to its effectiveness, antihistamine has been widely used in the treatment of allergic diseases, such as allergic rhinitis and urticaria by inhibiting histamine actions. Although antihistamines are generally safe, there are patients who experience unexpected side effects, such as sedation, cardiotoxicity, hepatotoxicity, nephrotoxicity, and change of appetite. Due to their ability to penetrate through blood-brain barrier, first-generation antihistamines potentially impair alertness, cognition, and memory. The safety profiles of the second-generation antihistamines are relatively superior to the first-generation antihistamines; the second-generation antihistamines cause relatively less central nervous system adverse reactions. However, serious cardiotoxicity of early second-generation antihistamines, such as terfenadine and astemizole, was reported. Moreover, widely-used second-generation antihistamine, cetirizine and loratadine, can present hepatotoxicity. In addition, body weight gain caused by both first- and second-generation antihistamines had been reported. In recent decades, pharmacologic mechanisms that are involved in these sides effect of antihistamine have been elucidated. Understanding detailed mechanisms and consequences of commonly observed side effects may help clinicians prescribe antihistamines safely. Herein, we summarize the mechanisms of histamine action, roles of antihistamines, and their common side effects in order to provide better understanding of antihistamines in clinical practice

첨단바이오의약품에서의 유전자치료제: 제품별 기전 및 안전성 비교

신주영,박주은,박다현,김서현,정선영 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

Globally, advanced therapy medicinal products (ATMP) such as stem cell therapies and gene therapies have become the focal point of the pharmaceutical market. In response to this trend, Korea, like the United States and Europe, has established various regulations and systems pertaining to ATMP. The Ministry of Food and Drug Safety enacted the ‘Act on the Safety and Support of Advanced Regenerative Medicine and Advanced Therapy Medicinal Products,’ restructuring the existing approval system from one centered around synthetic drugs and conventional biopharmaceuticals to one tailored to the characteristics of ATMP. While this regulatory framework allows for consideration of the unique attributes of ATMP, standardized safety measures specific to each product category are currently lacking. To address this gap, we provided foundational data for the safety and effective management of ATMP. This was accomplished by comparing and analyzing the mechanisms of gene therapy products, which are central to ATMP. Additionally, we conducted an analysis of indications and potential adverse events. Based on our research, we anticipate that our study will serve as foundational data for the safety and effective management of gene therapy. (PeRM 2024;16:11-17)

국내 자발적 부작용 보고 자료(KAERS)를 활용한 경구용 코로나19 항바이러스제 약물감시 연구

신주영,최윤주,박세정,김주환,윤동원,강동윤,정재훈 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

This study aimed to evaluate the association between nirmatrelvir/ritonavir, molnupiravir and adverse events and identify safety signals not previously known. Methods: To identify major adverse events and safety signals associated with nirmatrelvir/ritonavir and molnupiravir, we conducted pharmacovigilance study using drug-related adverse events reported to KIDS KAERS DB (2305A0011). Disproportionality analysis were performed using reporting odds ratio (ROR) and information component (IC) method to detected new safety signals not listed in drug label. Results: Adverse events related to nirmatrelvir/ritonavir and molnupiravir were frequently reported in women and person aged ≥ 65, and mostly reported as not serious. Following nirmatrelvir/ritonavir administration, ‘sensory abnormalities’ (20.18%), ‘diarrhoea’ (13.76%), and ‘nausea and vomiting symptoms’ (9.87%) were most commonly reported, while for molnupiravir, ‘nausea and vomiting symptoms’ (15.92%), ‘neurological signs and symptoms’ (15.92%), ‘urticarias’ (10.45%) were predominantly reported. Disproportionality analysis revealed a significant association of nirmatrelvir/ritonavir with ‘sensory abnormalities’ (ROR [95% CI] = 223.74 [207.24–241.55]), ‘interactions’ (ROR [95% CI] = 37.35 [15.10–92.35]), ‘faecal abnormalities’ (ROR [95% CI] = 32.33 [18.68–56.36]). Adverse events not listed on drug label included ‘olfactory nerve disorders’, ‘appitite disorder’, ‘hallucinations’ and urinary adverse events. For molnupiravir, strong association were observed with cardiovascular adverse events such as ‘heart rate and pulse investigations’ (ROR [95% CI] = 58.60 [18.96–181.16]) and ‘vascular tests’ (ROR [95% CI] = 10.97 [4.09–29.47]), which were not included in drug label. Conclusion: Adverse events following the use of nirmatrelvir/ritonavir and molnupiravir were generally not serious, but some safety signals not listed on drug label were newly detected and warranted attention. We expected this study to provide basic data of safety for oral antivirals of COVID-19 and may contribute to the development of future drug safety guidelines. (PeRM 2024;16:65-78)

국내 건강보험 청구자료의 활용 촉진을 위한 현안 및 개선방안

최남경,김희진,김동욱,김명규,김미숙,배승진,정선영,김예지,김정아,박수빈,조해린,신애선,신주영,안성복,안정훈,양보람,원희현,이승미,이희언,이중엽 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

While health insurance claims data in Korea have the potential as evidence for drug regulatory decision-making, its effective utilization remains limited. This study aims to identify the challenges encountered by researchers in utilizing claims data and discuss improvement strategies. We summarized practical difficulties encountered by researchers who have experience using claims data from the National Health Insurance Service and the Health Insurance Review and Assessment Service. Challenges encountered by researchers included difficulties in acquiring drug data, delays in data provision, limited provision of information on specific conditions, drugs, and treatments, small data capacity, short data usage periods, and spatiotemporal considerations when accessing data. To maximize the utility of claims data in drug regulatory decision-making, continuous communication between researchers and data providers is necessary for addressing these challenges. (PeRM 2024;16:1-10)

1차 의료기관에서의 약물안전시스템 인식조사

강동윤,이동엽,죄보윤,문승희,최은영 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

: The importance of effective adverse drug reaction (ADR) management in local clinics is increasing. This study investigates the current status of ADR management and reporting system use in local clinics, and opinions on development directions for effective ADR prevention. Methods: From January 11th to January 17th, 2022, an online survey was conducted targeting physicians working at local clinics regarding ADR management, use of reporting systems, and development of ADR prevention systems. Results: The awareness of the ADR reporting system was 54.50%, and 22.07% of respondents actually reported ADR incidents. The primary reasons for not reporting were ‘lack of time and unfamiliarity with the process,’ accounting for the highest percentage at 36.62%. Regarding sharing ADR information with other healthcare institutions, 88.56% responded that it would be helpful, and 66.49% indicated they could trust such information. The most crucial areas for improvement identified from the survey were the sharing of ADR records and national-level management. Conclusion: Creating an environment where local clinics can diligently report ADRs and establishing a system to share verified ADR information with other clinics will be a great help to national drug safety. (PeRM 2024;16:57-64

항암제별 과민반응 특성 및 전처치 요법

강혜련,이수연,김현지,정지웅 대한약물역학위해관리학회 2023 약물역학위해관리학회지 Vol.15 No.2

All antineoplastic agents can potentially cause hypersensitivity reactions. Hypersensitivity reactions to antineoplastic agents may not provide patients with optimal treatment and may affect future survival. Hypersensitivity reactions to antineoplastic agents are classified by time of onset of symptoms. If it occurs within 1–6 hours, it is classified as an immediate hypersensitivity reaction, and after 1–6 hours as a delayed hypersensitivity reaction. Mechanisms that cause hypersensitivity reactions to antineoplastic agents differ from drug to drug, and management strategies that match those mechanisms must be used. Management of hypersensitivity reactions to antineoplastic agents includes culprit antineoplastic agent withdrawal, administration after premedication, and desensitization of culprit antineoplastic agent. A better understanding of these management strategies can provide the best antineoplastic agent therapy for patients. In addition to this, it can prevent events leading to death and developing severe reactions. Although there have been many reports on the hypersensitivity reactions of antineoplastic agents, there are very few literatures detailing the hypersensitivity characteristics of individual antineoplastic agents. The purpose of this review is to improve the understanding of the hypersensitivity reactions of individual antineoplastic agents and to reduce the incidence of hypersensitivity reactions by proposing a premedication method.

노인의 퇴원 시 당뇨병 약제 강화 현황 및 단기 임상결과에 미치는 영향 분석

이주연,한주희,정애희,김민정,정선회 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

This study aimed to assess diabetes medication intensification at discharge in older adults hospitalized for non-glycemic reasons, examining its shortterm benefits and risks. Methods: A retrospective review of electronic medical records from Boramae Medical Center (September 1, 2020, to August 31, 2022) was conducted. Medication intensification was defined as either increasing the dosage of existing diabetes medications, adding insulin or initiating new medications. We compared glycated hemoglobin (HbA1c) levels 90 days post-discharge and the incidence of blood glucose-related emergency department visits or diabetesrelated unplanned readmission within 90 days post-discharge between patients with and without medication intensification. Results: Out of 1,278 patients, 480 (37.6%) underwent medication intensification at discharge. Factors associated with intensification included longer hospital stays, consultations with endocrinologist, higher HbA1c at admission, frequent hyperglycemic events, and changes in steroid or immunosuppressant use. The intensification group showed a significant reduction (8.6% to 7.0%) in HbA1c 90 days post-discharge compared to the non-intensification group (6.9% to 6.9%, p < 0.001). However, there was no significant impact on postdischarge emergency visits or unplanned readmissions related to blood glucose (aOR 0.34; 95% CI 0.07–1.53). Conclusion: A third of older adults admitted for nonglycemic issues was discharged with intensified diabetes medications, leading to improved short-term glycemic control but did not significantly affect diabetesrelated unplanned readmissions or emergency visits. (PeRM 2024;16:40-48)

페니실린 알레르기 꼬리표 떼기

이지향,강혜련,송수정 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

Penicillin allergy labels are associated with significant challenges, including antimicrobial resistance, restricted prescribing options, and negative outcomes for both patients and health care systems. However, only 10% of individuals labeled as penicillin allergic are found to be truly allergic after formal assessment. The evaluation process for a penicillin allergy encompasses a detailed allergy history, often followed by skin testing, and drug challenge. Researchers have suggested assessment tools and clinical decision rules for risk stratification for efficient and precise removal of incorrect penicillin allergy labels. In particular, patients categorized as low risk based on the assessment may undergo direct challenge test with penicillin, a practice supported by accumulating evidence. This comprehensive approach, emphasizing history taking and risk stratification, highlights the important role of healthcare providers in reducing the burden related to penicillin allergy labels. This review aims to understand the process of penicillin allergy evaluation and potential benefits of delabeling. (PeRM 2024;16:18-28)

스타틴 관련 근육이상반응 보고와 관련된 요인 식별을 위한 머신러닝 기반 클러스터링 분석

정선영,김정연,박세원,이민택,유승훈,이주원,남달리 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

: We aimed to identify factors associated with adverse event (AE) reports in statin-associated muscle symptoms (SAMS) using hierarchical clustering of patients in the Korea Institute of Drug Safety and Risk Management - Korea Adverse Event Reporting System database (KIDS-KAERS DB) (2105A0027). Methods: To explore the characteristics and risk factors of SAMS reports, we analysed the KIDSKAERS DB from 2016 to 2020. We included reports with a causality category level of “possible” or higher. Hierarchical clustering analysis was used to identify distinctive patterns within the dataset, with a particular focus on variables such as sex, age, statin type, contraindicated drugs and concomitant drugs. The reporting characteristics were described according to the cluster. Results: Four clusters of AE reports were distinguished by hierarchical clustering: atorvastatin- and rosuvastatinassociated AE (cluster 1), pitavastatin- and simvastatin-associated AE (cluster 2), rosuvastatin-associated AE (cluster 3), and atorvastatin-associated AE (cluster 4). Cluster 1 had a relatively higher proportion of men (57 cases, 50.9%) and a higher mean age (64.8 years) than the other clusters. Concomitant drug use was more common in cluster 1 (56 cases, 50.0%) than in other clusters (33.5%–46.2%), and all serious AEs were observed in cluster 1. Conclusion: Using hierarchical clustering, we found four distinct clusters based on SAMS report characteristics. Our findings further emphasize that patients prescribed statins, especially elderly male patients taking rosuvastatin and atorvastatin concomitantly with other medications, should be closely monitored for the development of rhabdomyolysis. (PeRM 2024;16:29-39)

공통데이터 모델과 임상 데이터 웨어하우스를 이용한 Fimasartan과 Losartan의 약물 유발 간 손상의 발생 비교: 단일 의료기관 후향적 코호트 연구

강혜련,윤진,김현지,고예희,이시연,안경민,정지웅,이지향,김광수 대한약물역학위해관리학회 2024 약물역학위해관리학회지 Vol.16 No.1

: Fimasartan, an angiotensin II receptor blocker (ARB) with superior potency and longer-lasting effects than losartan, demonstrates a good safety profile. However, recent case reports have emerged, linking fimasartan to hepatotoxicity. The aim of the study is to compare the occurrence of liver injury induced by fimasartan. Methods: Patients prescribed with fimasartan and losartan from 2011 to 2021 were identified from electronic health recordbased Common Data Model (CDM) of Seoul National University Hospital. Using clinical data warehouse, clinical information was collected and employed to cross-reference the results retrieved from the CDM. To assess causality and compare the incidence of drug-induced liver injury (DILI), 100 randomly selected patients with liver function abnormalities were evaluated. Results: The CDM analysis included 3,063 patients on fimasartan and 9,688 patients on losartan, among which 302 patients (2.37%) exhibited liver function abnormalities within the first year of ARB therapy. Specifically, 107 (3.49%) patients on fimasartan showed elevated serum alanine aminotransferase or aspartate aminotransferase, compared to 195 (2.01%) patients on losartan. However, when causality was assessed, patients with causality graded as probable or certain did not show any significant difference between the two medications. Conclusion: Although patients taking fimasartan exhibited a slightly higher incidence of mild liver enzyme elevations, this study did not find a significant difference in the occurrence of DILI. Consequently, fimasartan is less safe than losartan in terms of hepatotoxicity cannot be asserted. However, similar to other ARBs, fimasartan poses a risk of DILI, underscoring the importance of monitoring liver function tests to promote safer use of the medication. (PeRM 2024;16:79-89)