• Korean Journal of Clinical Pharmacy
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• v.32 no.4
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• pp.313-320
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• 2022

Background: Serotonin syndrome is a life-threatening disease if not appropriately treated. This study aimed to investigate the prescription status of contraindicated drug combinations that cause serotonin syndrome and identify the related factors. Methods: A cross-sectional study was conducted using nationwide claims data. Adult patients taking serotonergic drugs with Parkinson's disease or mental disorders were selected. Based on international medical databases (MDBs) and the Korean Drug Utilization Review (DUR), the status of prescribing contraindicated drug combinations that induce serotonin syndrome, the related factors, and the difference between international MDBs and the Korean DUR were analyzed. Results: Of the 49,773 study subjects, 163 (0.3%) were prescribed contraindicated serotonergic drug combinations based on international MDBs, and among them, only 105 (64.4%) were contraindicated by the Korean DUR. Positive influencing factors for prescribing contraindicated drug combinations include patient age between 65 and 74 and physician's specialties (neurologists, and orthopedists). Negative influencing factors were physician's specialty (internists) and medical institution (primary institutions). Conclusion: Despite the implementation of DUR, 3 out of 1,000 study subjects received contraindicated drug combinations that caused serotonin syndrome. Hence, it is necessary to comply with the DUR and improve it in accordance with international MDBs.

• Interdisciplinary Bio Central
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• v.5 no.2
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• pp.3.1-3.7
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• 2013

Recently, the productivity of drug discovery has gradually decreased as the limitations of single-target-based drugs for various and complex diseases become exposed. To overcome these limitations, drug combinations have been proposed, and great efforts have been made to predict efficacious drug combinations by statistical methods using drug databases. However, previous methods which did not take into account biological networks are insufficient for elaborate predictions. Also, increased evidences to support the fact that drug effects are closely related to metabolic enzymes suggested the possibility for a new approach to the study drug combinations. Therefore, in this paper we suggest a novel approach for analyzing drug combinations using a metabolic network in a systematic manner. The influence of a drug on the metabolic network is described using the distance between the drug target and an enzyme. Target-enzyme distances are converted into influence scores, and from these scores we calculated the correlations between drugs. The result shows that the influence score derived from the targetenzyme distance reflects the mechanism of drug action onto the metabolic network properly. In an analysis of the correlation score distribution, efficacious drug combinations tended to have low correlation scores, and this tendency corresponded to the known properties of the drug combinations. These facts suggest that our approach is useful for prediction drug combinations with an advanced understanding of drug mechanisms.

• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.239-247
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• 2013

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 co-administration, 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.21-27
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• 1995

This document collects Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH) guidance documents, citations to the primary literature, and other published and unpublished documents relevant to development and approval of drug/device combinations collected by the CDRH Division of Cardiovascular, Respiratory and Neurological Devices (DCRND). Since the Master Bibliography number represents an accession number, an alphabetical (by author) listing appears at the end of the document, Any citation marked with a, is on file in the DCRND offices, 340B, in the Piccard Building (HFZ-450), 1390 Piccard Avenue, Rockville, MD 20850.

• YAKHAK HOEJI
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• v.59 no.6
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• pp.278-283
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• 2015

The computerized prospective Drug Utilization Review (DUR) program supported by the Korean government has provided alerts to physicians and pharmacists since December 2010. This study aims to propose and apply the tiering system in "drug combinations to avoid (DCA)" and "age-precaution" alerts based on severity to improve the compliance of users. To propose the severity and clinical importance of 647 DCA alerts and 140 age precautions, a Delphi evaluation survey was conducted. An expert panel comprising 5 clinical pharmacists and 5 physicians were participated in mail surveys. Based on the results of Delphi survey, DCA pairs were classified into 3 groups; group 1 (70.6%), 2 (26.9%), and 3 (2.8%). Drug-age precaution ingredients were also classified into three groups; group 1 (53.6%), group 2 (40.7%), and group 3 (5.7%). When this grouping was applied to claim data from 2011 to 2013, the majority of alerts had occurred in the groups of high severity. Presenting DUR alerts with severity level is expected to improve the compliance of clinicians. The implementation of tiering system in DUR criteria should be considered.

• Korean Journal of Clinical Pharmacy
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• v.25 no.2
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• pp.120-129
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• 2015

Objectives: Drug utilization review program in Korea has provided 'drug combinations to avoid (DCA)' alerts to physicians and pharmacists to prevent potential adverse drug events or inappropriate drug use. Seven hundred and six DCA pairs have been announced officially by the Ministry of Food and Drug Safety (MFDS) by March, 2015. Some DCA pairs could be grouped based on the drug interaction mechanism and its consequences. This study aimed to investigate the drug-drug interaction (DDI) pairs, which may be potential DCAs, generated by the drug class-drug class interaction method. Methods: Eleven additive/synergistic and one antagonistic drug class-drug class interaction groups were identified. By combining drugs of two interacting drug class groups, numerous DDI pairs were made. The status and severity of DDI pairs were examined using Lexicomp and Micromedex. Also, the DCA listing rate was calculated. Results: Among 258 DDI pairs generated by the drug class-drug class interaction method, only 142 pairs were identified as official DCA pairs by the MFDS. One hundred and four pairs were identified as potential DCA pairs to be listed. QT prolonging agents-QT prolonging agents, triptans-ergot alkaloids, tricyclic antidepressants-monoamine oxidase inhibitors, and dopamine agonists-dopamine antagonists were identified as drug class-drug class interaction groups which have less than 50 % DCA listing rate. Conclusion: To improve the clinicians' adaptability to DCA alerts, the list of DCA pairs needs to be continuously updated.

• Journal of the Optical Society of Korea
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• v.19 no.4
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• pp.382-389
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• 2015

Motility contrast imaging is a coherence-domain imaging technique that uses cellular motility as a fully endogenous imaging contrast agent. Motility is measured inside tissue using a digital holographic coherence gate that extracts dynamic speckle from fixed depths. The dynamic speckle arises from the normal organelle motion inside cells, and from the movement of the cellular membranes driven by the cytoskeleton. It measures cellular activity and the effects of temperature and osmolarity. Motion is sensitive to cytoskeletal drugs, such as the antimitotic drugs used for cancer chemotherapy, and the effects of drug combinations also can be monitored. Motility contrast imaging is a potential tissue-based assay platform for highthroughput screening of pharmaceuticals.

• Korean Journal of Clinical Pharmacy
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• v.24 no.2
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• pp.126-134
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• 2014

Purpose: This study was aimed to examine the financial effect of 2-tiered copayment system on annual expenditure of pharmacy benefit in the National Health Insurance (NHI) of Korea, focusing on oral antidiabetic medications. Methods: 284 oral antidiabetic products with 14 different active single ingredients listed in the National Formulary of NHI (August 2009) were assigned to tier 1 or tier 2 according to the selected criteria. 10 different combinations of coinsurance rates were selected to estimate the changes in drug expenditure cost of NHI. Results: The annual drug cost was estimated based on the drug price per unit listed in the National Formulary and the used amount of products in 2009 from the IMS Health data of Korea. In the combinations of coinsurance rate of 20% for tier 1 and 40% for tier 2, the total annual drug cost was estimated to be reduced by 1.3% in the case of no change of generic and original drug consumptions, and to be reduced by 4.3% in the case of 10% increased generic drug consumptions. Conclusion: The tiered copayment system with optimal coinsurance rates appears to be a potential strategy to reduce the financial burden of NHI in Korea by promoting the use of generic products.

• Korean Journal of Clinical Pharmacy
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• v.33 no.4
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• pp.242-253
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• 2023

Background: Arrhythmia due to QT prolongation is one of the most serious adverse events with drug interactions in the elderly. This study aimed to examine the incidence of arrhythmia in Korean elderly patients who administered both cytochrome P450 3A4 (CYP3A4) substrates and inhibitors. Methods: Patients using CYP3A4 substrate and inhibitor were selected from the 2017 elderly patient dataset (the Korean Health Insurance Review and Assessment Service - Aged Population Sample). Selection criteria were patients with a medication possession ratio over 80%, medication duration of at least 7 days, and a follow-up period of 3 months or more. The patient's basic information is age, gender, health insurance type, and comorbidities. The top 50 drug pairs and comorbidity with high-incidence arrhythmia were presented. Results: In patients with drug combinations for over 7 days, there were 981 incidences of arrhythmia, and 351 incidences in those with combinations for over 30 days. The comorbidities of congestive heart failure and myocardial infarction had a significant association with incidence of arrhythmia. Among patients with 7 days or longer, the drug pairs [substrates-inhibitors] with significant adjusted odds ratio (aOR) were [propranolol-cimetidine] (aOR, 2.25; 95% confidence interval [CI], 1.66-3.04). Among patients with 30 days or longer, the drug pairs with significant aOR were [tramadol-amiodarone] (aOR, 2.87; 95% CI, 1.97-4.19). Conclusions: In elderly patients, the incidence of arrhythmia was high with drug interactions of CYP3A4 substrates and inhibitors. The comorbidity of congestive heart failure was the risk factor.

• Journal of Radiation Protection and Research
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• v.7 no.1
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• pp.11-16
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• 1982

Cysteamine(Mercaptoethyiamine, MEA), S,2-Aminoethylisothiouronium Bromide. HBr (AET), and S-(2-Aminoethyl) Dihydrogen Phosphorothioate (WR-638) were prepared and radioprotective effects of these chemicals and their combinations against $^{60}Co$ ${\gamma}-ray$ radiation were studied ,in irradiated ICR mice. Intraperitonially administered chemicals or their combinations resulted drug deaths in cases of MEA, AET, and their combinations, whereas there were a slight or no drug death in cases of WR-638 and the combination of AET with WR-638. All tested chemicals and their combinations yielded radioprotective effects against $^{60}Co$ $\gamma-ray$ radiation. An additive radioprotection effect was observed in case of the combination of AET with WR-638.