Earticle

This study aims to explore the difficulties of evidence-based pharmaceutical policy-making in the Korean context where several pharmaceutical policies were introduced within a short period. Semi-structured in-depth interviews were performed with eight experts in the Korean pharmaceutical arena. The key challenge in Korean situation might be the apparent lack of available evidence caused by the limited resources, the lack of policy consistency and coordination ability in the authorities and distrust across stakeholders. To build an evidencebased tradition, it is essential to resolve the tangible lack. At once, more fundamental changes seem to be required in the intangible policy environments.

Background: Many factors including drugs, dietary supplements, and food intake can affect the development and organ formation of fetuses. Because of this, subject tends to avoid consuming things like coffee, alcohol, or cigarettes due to the risks they pose during pregnancy. Therefore, analysis of drugs and favorite food consumption is needed and important to ensure safe health management for subject. Purpose: This study was conducted domestically to analyze these factors in South Korea. Method: The survey was conducted from pregnancy-related online communities for six days and the survey results were received via email for analysis. Result: A total of 127 subjects answered the questionnaire via email; the characteristics of subjects are widely varied in their ages, education levels, job statuses, and residences. The questionnaire included the intake of dietary supplements during pregnancy including vitamins and the result showed that the subjects took 2.23 different kinds of supplements on average. In order of highest frequency, 101 subjects took multivitamins; 79 subjects took an iron supplement; 30 subjects took analgesics; 20 subjects took prescribed antipyretic and medication for upper respiratory diseases; 12 subjects took antibiotics; 7 subjects took antiemetics. Their compliances were different in each medication categories. Only 8% of subjects answered that they had asked a pharmacist for medication information during pregnancy. In addition, 78% of subjects answered that they never counseled with anyone about pregnancy related medication use. Conclusion: In conclusion, many subjects took medication including dietary supplements. The role of pharmacists should be actively developed to improve subject care such as education about subject’s medication uses and their food consumption behavior.

Purpose: The aim of this study was to investigate the effect of nimodipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Methods: Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of nimodipine (0.5 or 2 mg/kg) in rats. The effect of nimodipine on the P-glycoprotein as well as cytochrome P450 (CYP) 3A4 activity was also evaluated. Results: Nimodipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration (IC50) of 10.2 μM. Compared to those animals in the oral control group (warfarin without nimodipine), the area under the plasma concentration–time curve (AUC) of warfarin was significantly greater (0.5 mg/kg, P<0.05; 2 mg/kg, P<0.01) by 31.3-57.6%, and the peak plasma concentration (Cmax) was significantly higher (2 mg/kg, P<0.05) by 29.4% after oral administration of warfarin with nimodipine, respectively. Consequently, the relative bioavailability of warfarin increased by 1.31- to 1.58-fold and the absolute bioavailability of warfarin with nimodipine was significantly greater by 64.1-76.9% compared to that in the control group (48.7%). In contrast, nimodipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Conclusion: Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism rather than P-glycoprotein-mediated efflux by nimodipine.

Purpose: The aim of this study was to investigate the current state of antidepressant prescriptions in breast cancer patients and factors affecting the prescription of antidepressants. Methods: This study targeted female breast cancer patients who were prescribed antidepressants by a psychiatrist at least once between August 2010 and July 2011 at the Asan Medical Center in Seoul. The prescription history of each study subject was investigated to analyze the current state of antidepressant prescriptions in breast cancer patients. Results: The analysis of the prescription histories of 136 subjects in the antidepressant group determined that escitalopram, mirtazapine, and trazodone were the three most commonly prescribed medications with an average of 1.54 antidepressants prescribed per patient. A logistic regression analysis showed a statistically significant increase in antidepressant prescriptions in patients who were divorced or widowed, had sleep disturbances, or had undergone oncologic surgery for the breast cancer (p<0.050). In contrast, the prescription rate was lower for patients with tumour sizes greater than 50 mm (p<0.050). Conclusion: The sociodemographic factor of marital status, clinical factors of sleep disorders and tumour size, and a treatment-specific factor of the use of surgical therapy were identified as affecting the prescription of antidepressants in female breast cancer patients.

Objective: This study aimed to identify the status and risk factors of rituximab infusion-related adverse events (ADE) in rituximab-naïve patients with cancer diseases. Method: A retrospective analysis using electronic medical records review was conducted. Inclusions were patients with a diagnosis of cancer disease with the initiation of rituximabincluded treatment who were naïve to rituximab during January 2011 to March 2013 at National Cancer Center (NCC) in Korea. Result: Total 110 patients, 582 cases of rituximab administrations, were reported in the study. About 57.2% of patients were 51-70 years old and evenly distributed between two genders and 72.7% were BMI less than 25 kg/m2. All of study patients were diagnosed with non-Hodgkin lymphoma. Fifty patients (45.4%) and 54 cases (9.3%) were experienced rituximab infusion-related AEs even with conservative administration protocol at NCC. The most frequently occurring AEs were shivering followed by rash and itching. In single variant analysis, we found that the early stage of NHL, low exposure to rituximab administrations, high white blood cell counts, high lymphocyte counts, high absolute neutrophil count and low lactate dehydrogenase were associated with infusion-related AEs (p<0.05). The early stage of disease, high lymphocyte counts, low exposure to rituximab administrations were also related significantly with AEs in multiple variants analysis (p<0.05). Conclusion: Rituximab infusion-related AEs for patients who were naïve to rituximab were still a concern with conservative administration protocol. The adverse drug reactions were significantly associated with early stage of NHL, higher lymphocyte counts and low exposure to rituximab administrations. The factors need to be considered with close monitoring to prevent rituximab infusion-related AE.

Background: Although thromboembolism is common and one of the major causes of mortality in cancer patients, maintaining therapeutic anticoagulation effect with warfarin is challenging. This study aimed to determine the prevalence and the causes of non-therapeutic INR (International Normalized Ratio) in cancer patients. Methods: Medical and pharmacy records for cancer patients managed by the pharmacist-run anticoagulation service (ACS) between May, 2010 and April, 2011 at Seoul National University Hospital were retrospectively reviewed. The causes of non-therapeutic INR were identified and compared with the results from a former study with mechanical heart valve patients. Results: A total of 335 cancer patients and 6,737 patient-visits were analyzed producing 68% (n=4,590) of non-therapeutic INR readings. Eightyfive percent of the non-therapeutic INR readings were categorized as sub-therapeutic. Frequent causes linked to non-therapeutic INR included inadequate dosage adjustment (21.8%), changes in health status (11.8%), dietary changes (8.1%), and drug interactions (4.2%). More than half of the non-therapeutic INR values had no known etiology. As causes for non-therapeutic INR, changes in health status (p<0.0001), adverse reactions (p<0.0001), and dietary changes (p=0.017) were statistically more frequent in cancer patients than in patients with mechanical heart valves. Furthermore, exposure to sub-therapeutic INR were more prevalent in cancer patients than in patients with mechanical heart valve (p<0.0001). Conclusions: This study shows that there is a tendency to keep the level of INR low and that health status change, dietary change, and drug interactions are found to be frequent causes for non-therapeutic INR in cancer patients.

Background: Fixed drug combinations are formulations containing two or more active ingredients in a single dosage form. Such combination therapies are commonly applied to improve efficacy, reduce adverse events and replace coadministration, etc. National and international guidelines for hypertension treatment recommend addition of other classes of antihypertensive drugs rather than incremental dose of mono-therapy, when blood pressure is not adequately controlled. Thus, many dual combinations of antihypertensive drugs have been approved and pharmaceutical companies are recently interested in developing antihypertensive triple combinations. Clinical trial designs for the fixed combinations are various depending on the target patients, dosage and clinical endpoints. Thereby, further discussions for the clinical trials of antihypertensive triple therapies are required regarding the indication claimed. Conclusion: This article provides a review for the assessment of the label and medical reports of the clinical trials on antihypertensive triple therapies in advanced foreign countries.

Objective: This paper was aimed to investigate the current labelling trend of tar color additives in infant’s drugs used in Korea and other countries. Method: The current labelling system of the tar color additives in infant's drugs was investigated using inserted papers for drug information of infant’s drugs as well as three drug information internet sites popular in Korea including internet sites of foreign countries of USA, UK, Japan, and China for infant’s drug information. Results: Among 325 drugs registered as syrup form for infant’s drugs (sources, http://www.health.kr), 4 drugs indicated tar color related information on the internet and only 2 drugs indicated tar color additives’ name. And from the investigated results of 76 inserted papers for infant’s drug information, among 31 drugs containing tar dyes, in only 19 drugs the tar color additives’ names were notated. Among 6 drugs which do not contain tar dyes, only 1 drug was notated as ‘Dye-Free’. Conclusion: For advanced labelling system in Korea, we proposed the below guidelines. [1] The name of tar color additives used in infant’s drugs should be notated even in drug information on internet sites. [2] All drug ingredients used in infant’s drugs need to be separately notated as active and inactive species on both internet sites and inserted papers. [3] ‘Dye-Free’ notation should be mandatory for infant’s drugs which do not contain tar color additives in drug information on the internet sites as well as inserted papers.

Objective: To study the attitudes and awareness of healthcare professionals (physicians, pharmacists, nurses and others) toward the Pharmacovigilance system and experience for adverse drug reactions (ADRs) from a Single University Hospital in Deajeon. Methods: A survey was performed using a structured questionnaire involving 360 health-care professionals at the hospital between 1st November and 16th November, 2012. Results: Sixty-five percent (n=235) of all respondents were experienced incidences of ADRs for their patients and 55.8% (n=201) knew the ADR Spontaneous Reporting System in the hospital. However, three-fourths (n=273, 75.8%) of respondents did not know the existence of the Korean Association of Regional Pharmacovigilance Centers (KARP) and 61.7% (n=222) were unaware of the obligation of ADR report from KFDA in cases of serious ADRs. About 83% (n=299) answered that the electronic ADR report system of the hospital was helpful while their work and most (n=336, 93.3%) agreed on the necessaries of the promotion and education about ADR. Conclusion: Seventy-five percent (n=271) of respondents wanted to continue the work for evaluation and feedback for ADRs reported in the hospital. However, the barriers to reporting ADR were; inconvenient ADR reporting system and the lack of time to report ADRs. This study showed that the easier ADR reporting system and education and promotion about ADRs for health-care providers are needed to improve the ADR reporting.

Objectives: The purpose of this study was to identify the factors which affect risk perception and attitude on government risk management over medications containing asbestos among parents of elementary school students. Methods: This research design was cross-sectional study using self-administerd questionnaire. The survey subjects were parents of elementary school students in Seoul, total of 1,051 subjects. The survey period was from June through July of 2011. The collected data were analyzed using the SPSS 20.0. Results: The subjects perceived high risk regarding medications containing asbestos. About 83.6% of the subjects perceived that the result taking of medications containing asbestos was fatal, 82.8% felt that medications containing asbestos was a very serious social problem, 79.5% agreed that medications containing asbestos was a new type of threat. The risk perception for medications containing asbestos was related to political affiliation, attitudes of dealing medicines, main use of media, and personal communication credibility. Those who did not believe that the current government policy was correct and the government was working toward the public's benefit and not its own had the higher level of negative attitudes towards the government’s risk management over the case of medications containing asbestos. Conclusion: In implementing government policy, all information should be efficiently and accurately communicated through a transparent implementation process. Also, the government must have plans for countermeasures in case of an emergency and respond efficiently in order to maintain their credibility. Moreover, this highlights the need for health authorities to exert more effort in increasing public education/awareness, especially those concerning drug and dug-taking behavior, in order to harness positive attitude and trust towards the government’s policy. For a more effective risk communication, the media, health experts, government representatives, and related industries should work together.

Background: Problem-based learning (PBL) has introduced as an importnat part of pharmacy education in Korea as it is effective method to help students gain and apply knowledge with development of problem-solving, critical-thinking, and decision-making skills. In order to provide the effective PBL, a number of trained facilitators and suitable PBL rooms are required. However, these become a barrier in Korea as most pharmacy schools have one or two faculty members who majored in clinical pharmacy. Objective: This study was perfomed to implement and evaluate a modified PBL in gastrointestinal (GI) pharmacotherapy class facilitated by one instructor. Methods: A general information of traditional PBL for 6 hours through 3 days is introduced before initiatiing GI pharmacotherapy class. After 3 hour-GI pharmacotherapy classes for 6 weeks, modified PBL was implemented with one instructor to facilitate PBL for four small groups with 19 pharmacy students simultaneously. Modified PBL was incorporated with weekly mini-case discussion and presentation. Results: Students completed 15-question survey to evaluate modifed PBL course, student performance, group performance, and facilitator performance. Eighty-four percent of students answered modified PBL was helpful to understand what they have learned. Mean score in group performance was higher than that of individual performance during modified PBL course. Overall, students reported modified PBL was useful in knowledge building. Conclusion: Modifed PBL model without individual group facilitators in one classroom helped students to achieve selfdirected, independent learning skills in an interactive and engaging environment.