Signal Detection of Alpha-adrenoceptor Antagonist using the KIDS-KAERS database (KIDS-KD)

Background@#Using KIDS-KAERS database (KIDS-KD) from 2016 to 2020, the aim is to investigate signals of adverse events of alpha-adrenoceptor antagonists and to present adverse events that are not included in the precautions for use when marketing approval. @*Methods@#This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of alpha-adrenoceptor antagonists, such as terazosin, doxazosin, alfuzosin, silodosin, and tamsulosin. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). Detected signals were compared with product labeling and the European Medicines Agency-Important Medical Events list. @*Results@#Out of the total number of 408,077 reports for adverse events, 6,750 cases were reported as adverse events of alpha-adrenoceptor antagonists. Dizziness, mouth dryness, hypotension postural, and oedema peripheral are identified as common adverse events of five alphaadrenoceptor antagonists and are typically listed on drug labels. However, new signals were detected for pneumonia, chronic obstructive airway disease, eye diseases such as glaucoma and cataracts, fracture, and ileus of tamsulosin that were not previously listed on the drug labels in Korea. @*Conclusions@#This study identified signals related to adverse drug reactions of alpha-adrenoceptor antagonists and presented serious adverse events, suggesting new adverse reactions to be aware of when using alpha-adrenoceptor antagonists.

Class duplication prescriptions in patients taking fixed-dose combination antihypertensives

Background@#Fixed-dose combinations have the advantage of improving patient compliance, but may increase the risk of duplicate prescriptions. As the use of fixed-dose combination antihypertensives increases, it is necessary to investigate the current status of class duplication prescriptions (CDP) in patients taking fixed-dose combination antihypertensives in Korea and to identify factors associated with CDP. @*Methods@#We conducted a retrospective observational study using nationally representative claim data. Hypertensive patients aged 20 years or older taking fixed-dose combination antihypertensives were extracted. Among these patients, patients with CDP were identified. A chi-square test was applied to determine the differences between patients with CDP and nonCDP. The associated factors of CDP were identified through multiple logistic regression. @*Results@#Of the 74,165 patients who were prescribed fixed-dose combination antihypertensives, 426 patients (0.6%) with CDP were identified. The most common antihypertensive class associated with CDP was calcium channel blockers (194 patients, 45.5%), followed by angiotensin II receptor blockers (136 patients, 31.9%). Patients aged 75 years or older (odds ratio [OR] 1.83, 95% confidence interval [CI] 1.02-3.52), chronic kidney disease (OR 4.45, 95% CI 2.15-8.25), chronic heart failure (OR 2.71, 95% CI 1.93-3.72), coronary artery disease (OR 2.22, 95% CI 1.60-3.03) and Medical Aid/Patriots and Veterans Insurance (OR 1.49, 95% CI 1.04-2.07) were significantly associated with increased CDP. @*Conclusions@#The factors associated with CDP were the elderly, comorbidities, and low socioeconomic status. Since CDP can result in negative clinical outcomes, active intervention by the pharmacist is warranted.

Clinical Information on Green Tea Extract Used for Weight Loss

BACKGROUND: Green tea extracts are approved as nonprescription drug and available as health functional foods, health foods, and beverages. Clinical information on the products is lacking. METHODS: Information about the products on green tea nonprescription drugs was obtained from the website of the Korea Pharmaceutical Information Center. The Naver, i.e., a top ranking online search portal, was used for compiling the list of the health functional food products using key words of ‘green tea catechin’ on August 23, 2018. The recommended daily dosages of catechins were calculated as 30% of the total dried mass of green tea and about 50% of the catechins were considered as epigallocatechin gallate (EGCG). RESULTS: A total of two types of nonprescription drugs containing green tea powder or extracts, nine health functional food products, and three types of health foods were found. The regulatory requirements of the EGCG exceeding 800 mg were reported to be associated with adverse effects of elevated liver enzyme. If consumers take several green tea products concurrently, such as nonprescription drugs with health functional foods or health foods, it could exceed the recommended amount of EGCG. CONCLUSION: The concurrent use of green tea products as nonprescription drugs, health functional foods, and healthy foods may lead to an increased exposure to EGCG. Pharmacists should be aware the availability of various types of green tea products and the potential risk of liver toxicity due to excessive consumption of EGCG.

A Review on Efficacy and Safety of SGLT2 Inhibitors as Add-on Therapy with Metformin

BACKGROUND: The new type of diabetes treatment, SGLT2 inhibitors, has been approved for monotherapy and combination therapy, but medical insurance is only allowed in combination therapy with metformin, which is the first choice for type 2 diabetes treatment. METHODS: The SGLT2 inhibitors prescribed in Korea are dapagliflozin, empagliflozin and ipragliflozin. A review was conducted using Pubmed to evaluate efficacy and safety for these medications with metformin combination therapy. 10 studies were selected by searching for keywords and related references and were reviewed in full. The mechanism of action, pharmacokinetics, and the economics of treatment with SGLT2 inhibitors were examined. RESULTS: SGLT2 inhibitors had moderate glycemic control when added to the treatment of patients with type 2 diabetes who were not being regulated by metformin monotherapy. They also showed positive effects such as weight loss, as well as the lowering of blood pressure. Hypotension and serious side effects were relatively low. However, the risk of genital infection was increased. CONCLUSION: The SGLT2 inhibitors are a new class of drugs that promote glucose excretion in the urine. They are a good choice for combination therapy with metformin for the treatment of type 2 diabetes, with weight loss and very low risk of serious side effects.

Fentanyl PCA Monotherapy and Fentanyl TTS Combination Therapy in Post-Operative Pain Management: Analyses of Spontaneous Adverse Drug Reaction Reports

OBJECTIVE: There have been many cases of spontaneous adverse drug reactions to fentanyl at a regional pharmacovigilance center in the hospital. To assess the factors causing the adverse drug reactions reported in patients receiving fentanyl patient-controlled analgesia (PCA) monotherapy or in combination with fentanyl transdermal therapeutic system (TTS) for acute post-operative pain management. METHODS: We conducted a retrospective cohort study with all patients prescribed fentanyl PCA for pain management after orthopedic surgery at a single university hospital from June 2012 to May 2013. We analysed the factors causing adverse drug reactions reported by a spontaneous reporting system in patients receiving fentanyl PCA monotherapy and those receiving fentanyl TTS in combination with fentanyl PCA. RESULTS: Based on the spontaneous adverse drug reaction reporting, the risk ratio for the incidence rate of adverse drug reaction in the fentanyl TTS combination therapy group was 3.04 (95 % CI: 2.4-4.00, P < 0.0001), which was approximately 3-fold higher than that reported for fentanyl PCA monotherapy. Only 60 % of the adverse drug reactions were reported. CONCLUSION: It is inappropriate to add fentanyl TTS to fentanyl PCA to manage post-operative acute pain. There is a need to improve adverse drug reaction reporting. We expect that regular analysis of adverse drug reactions reported at regional pharmacovigilance centre would aid in appropriate drug utilization by patients.

Middle East Respiratory Syndrome Outbreak and Responsiveness of the Pharmacy Programs on the Pharmacy Practice Education

BACKGROUND: Pharmacy curriculum change was made from a 4-year program to a 2+4 year program in year 2009 in Korea. The change has resulted in more educational exposures on patient-centered practice environments for about 1,400 hours in the last year of the professional pharmacy program. When the Middle East Respiratory Syndrome (MERS) outbreak hit Seoul and suburban areas and propagated to other provinces in Korea, emergency response to avoid student infection in the pharmacy practice sites became an urgent issue. While other health professional programs such as medicine and nursing had activated emergency preparedness manuals, timely and clear guidelines were not disseminated to all pharmacy programs and protective measures largely relied on individual pharmacy program. METHODS: A survey was developed by the Committee on Pharmacy Practice Experience Programs in the Korean College of Clinical Pharmacy to document the status of pharmacy programs during the Korea MERS outbreak in 2015. The 10-question survey was distributed to the pharmacy practice experience coordinators to 34 out of 35 pharmacy schools in Korea by emails. RESULTS: Our findings showed that 82.4% of the program coordinators (28/34) responded to the survey, 96.4% of the programs did not have emergency preparedness manuals, administrative meetings were held in 89.3% of the pharmacy programs, the rotation schedules were modified or withheld in 53.6% of schools, and the changes were mostly observed from the programs classified as MERS outbreak regions. CONCLUSION: Further needs in establishing the emergency preparedness manual should be explored for pharmacy education stakeholders.

An Analysis on Prescribing Patterns of Antidepressants and Their Associated Factors in Lung Cancer Patients

BACKGROUND: Depression is the leading cause of lowering the quality of life of cancer patients and lung cancer is the most likely to cause depression. It is necessary to find out depression-related factors in lung cancer patients. METHODS: The study was a retrospective cohort study using medical records, and was a non-equivalent comparison group design. It involved patients diagnosed of lung cancer at the Konkuk University Medical Center from January to December 2012. Between antidepressants prescription group and non prescription group, socio-demographic factors, clinical factors, treatment-related factors and other factors were analyzed statistically. RESULTS: Antidepressant prescription group consisted of 23 people and non-prescription group of 206 people. Prescription rate of quetiapine was the highest 47.8% (11/23), followed by escitalopram (43.5%, 10/23), amitryptyline and trazodone (30.4%, 7/23). The prescription group was prescribed with an average of 1.9 antidepressants. Antidepressants were prescribed after average of 248 days from lung cancer diagnosis and prescription period per patient was average 177.5 days. According to the result of univariate logistic regression analysis between 2 groups, factors such as number of outpatient visit, number of admission, days of hospitalization, sleep disorder, and comorbidity were found to be statistically significant (p < 0.05). However, According multivariate logistic regression analysis showed that number of admission, days of hospitalization and sleep disorder were statistically significant (p < 0.05) excluding comorbidity. CONCLUSION: About 10% of lung cancer patients had received a prescription for antidepressants after lung cancer diagnosis. A sleep disorder, number of hospitalization and length of stay were identified as factors influencing the prescribing antidepressants.

A Systematic Review on Drug Safety for Molsidomine, Nicorandil and Trimetazidine

BACKGROUND: Ischemic heart disease is the most common type of heart disease and an important cause of death in Korea. Among marketed anti-anginal medications, molsidomine, nicorandil, and trimetazidine are approved in Korea with unique mechanism of actions. As these drugs are not approved by the US Food and Drug Administration, the access to the up-to-dated and comprehensive safety-related information has been less than optimal from drug information resources used by Korean pharmacists. METHODS: A systematic review was conducted using Embase and Korean manuscripts to compile safety updates for these medications. Out of 418 articles from keyword searches, 52 studies were reviewed in full to compare adverse effects (AEs) with the approved package inserts (PI). RESULTS: Molsidomine related adverse effects were mostly mild or moderate, but anxiety, palpitation, epigastric pain, and sexual potency reduction were additional AEs found from the review not listed in PI. Although PI has included ulceration in oral cavity and gastrointestinal tracts including anus by nicorandil, the Korea FDA recently recommended adding corneal, genital, and skin ulcers to the approved PI. Trimetazidine induced Parkinsonism, worsening of the symptoms for patients diagnosed with Parkinson's disease, gastrointestinal burning, and muscle cramps were additionally identified AEs not listed in PI for trimetazidine. CONCLUSION: Continuous evaluations of the safety profile of these agents are needed to balance the risks and benefits to provide evidence-based safety counseling to the patients. In addition, more focused efforts on spontaneous reporting are warranted by healthcare professionals to safeguard patients against AEs.

Oversight on the Bioethical Compliance of National R&D Projects or Research Personnel

BACKGROUND: Oversight on the bioethical compliance of national R&D projects or research personnel is currently conducted exclusively by IRB (Institutional Review Board) within the relevant research institute. Considering current state of affairs in Korea, there is an imperative to establish a national oversight system for bioethical compliance, conduct comprehensive oversight on bioethical compliance of national R&D projects, and enhance subject protection system. METHODS: We examined opinions from researchers and IRB personnels regarding ethical oversight system on R&D projects. Additionally, we looked at IRB assessment by KAIRB (Korea Association of Institutional Review Board) in order to identify status and problems with current IRB system in Korea. Assessment was also done for four other countries (US, UK, Germany, Singapore) through in-person visits as well as surveys in writing for a total of 6 months (2012.12.1~2013.5.31). The research comprised of two aspects: system management and R&D project audit. Based on this, we examined current status and problems of the existing system in Korea and made recommendations for improvement. RESULTS: Regulatory objectives and backgrounds of biomedical researches are different from each country due to different characteristics of bioethical oversight system. This shows that each country sets up its own regulations and procedures to fit each situation. Bioethical compliance oversight system greatly varied between the countries. From this study, it can be seen that improvement of existing procedures and oversight system or establishment of new ones are essential in Korea. CONCLUSION: In terms of system management, a dedicated government organization need to be established for bioethical compliance, subject protection, IRB inspection, training, evaluation, and certification of systems, and also support for IRB e-system. Regarding R&D project oversight, it is essential to confirm IRB review results before start of a research, to conduct a review on ethical aspects of research plans, and to carry out continued oversight on bioethical compliance through interim reports.

Evaluating Appropriateness of Medication Use in the Operating Rooms of a Tertiary Hospital: Based on Survey

BACKGROUND: Since the use of opioid analgesics is frequent in operation rooms (OR), the risk of medication error is high; however the use of medication in the OR has been operating independently with the hospital pharmacy. Therefore, the assessment on management of medication use in operation and the pharmacist's role is needed. METHODS: We conducted the literature review and survey from anesthesiologists, operating nurses at Chung-Ang Hospital on management of medication for operation use, awareness on need for medication management efficiency, need for satellite pharmacy in the operating room and its effect. RESULTS: 56% of medical staffs responded that management of medication in the operating room is efficient; however, 82.6% responded that they felt the inconvenience in medication delivery to the OR when additional prescription was ordered. 51.5% also responded that extra time was required for management of narcotics and inventory/record keeping. 80% agreed that there could be lost costs due to prescription missed. Medical staffs responded improving the drug management system could increase the OR efficiency (87%), and eventually bring the increase in hospital revenue (80.4%). Those who responded that implementation of OR satellite pharmacy was needed include physicians (84.6%), nurses (63.6%), and also responded that it'd bring more profit to the hospital by increasing the efficiency in OR (60.9%). CONCLUSION: For efficient management of medications, implementation of OR satellite pharmacy would lead to improved drug management and increased efficiency in OR and reduced cost and improved patient care.

Prescription Patterns and Appropriateness of Topical Mupirocin in Ambulatory Care using the Korean National Health Insurance Claims Database

BACKGROUND: Mupirocin, a topical antimicrobial agent has been used for patients with methicillin-resistant Staphylococcus aureus and recently mupirocin resistance was issued in some studies. The objective of this study was to analyze prescription patterns of topical mupirocin, to evaluate appropriateness of prescriptions in the ambulatory setting, and to compare frequency of mupirocin usage in South Korea with that in United States. METHODS: Topical mupirocin prescription patterns (the number of prescription and a prescription period), and appropriateness of prescription (including a prescription rate over 10 days, a repeat prescription rate within 30 days and a prescription rate within labeled indications) were analyzed using the 2012 Health Insurance and Review and Assessment service-National Patient Sample dataset of South Korea. The National Ambulatory Medical Care Survey dataset was used to quantify topical mupirocin prescription in United States for comparison. RESULTS: In South Korea, the prescriptions rate for use over 10 days was 3%, the repeat prescription rate within 30 days was 8.87% and the prescription proportion within labeled indications was 33.84%. The most frequent diagnostic code was nonbacterial infection. The prescription rate per 1000 population of topical mupirocin in South Korea was calculated to be 46.07, whereas in United States was calculated to be 13.10. CONCLUSION: Topical mupirocin has been used frequently and inappropriately, so further studies are required to investigate the rationale behind such prescribing mupirocin patterns.

Two Cases of Neonatal Adrenal Hemorrhage

No abstract available.