• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.129-136
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• 2013

Objectives: Among many new drugs that are under investigation with intent to treat cancer, oral kinase inhibitors are proven to be effective in numerous clinical trials and easy to administer. Due to these advantages the use of oral kinase inhibitors is increasing. Oral kinase inhibitors are metabolized by CYP450 which can result either increase of adverse effect or decrease of drug effect by drug interaction when used concurrently with other agents. In this research, the medication records of patients on oral kinase inhibitors from Oct. 2010 to Nov. 2011 were reviewed to investigate potential drug interactions. Methods: From Oct. 2010 to Nov. 2011, cancer patients in Inha University Hospital who took oral kinase inhibitors more than once were included. The patients' medication records were reviewed to list out concurrent medications that have interaction potential with oral kinase inhibitors, the frequency of concurrent use, and the severity of interaction result using Micromedex$^{(R)}$ and Lexicomp-online$^{(R)}$ as references. Results: As a result, 90 cases of drug with interaction potential were prescribed by Micromedex$^{(R)}$ and 179 cases by Lexicomp-online$^{(R)}$ data. In case of severity, 33.3% by Micromedex$^{(R)}$ and 26.3% by Lexicomp-online$^{(R)}$ were categorized as Major and 65.6% by Micromedex$^{(R)}$ and 72.6% by Lexicomp-online$^{(R)}$ as Moderate. The number of adverse events was 92 cases which 58.7% were on skin and 19.6% on Gastro-intestinal tract. Conclusions: Considerable number of drug with interaction potential was used though each oral kinase inhibitors showed differences in extent. Hence there exists the risk of drug interaction in patients taking oral kinase inhibitors with other drugs.

• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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• pp.1-17
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• 2009

Adverse drug reactions (ADR) caused by inappropriate prescription are responsible for major socioeconomic loss. Drug-drug interactions (DDI) has been recognized as a major part of ADRs and, therefore, healthcare professionals should prevent possible DDIs to minimize preventable ADRs. This study aimed to examine DDI information in drug information references and Korea Food & Drug Administration (KFDA) drug labeling information. Drug ingredients from the formulary of Health Insurance Review and Assessment Service in Korea (HIRA) were included for the study. DDI information source used for the study were Micromedex Drugdex and Drug Information Facts (DIF) with the DDI severity level of "moderate" or more. The DDI information in KFDA drug labeling were collected and compared. Drug ingredients were classified with KFDA Drug Classification and ATC Classification of WHO for the analysis. Among the total 1,355 drug ingredients satisfying inclusion criteria, 738 ingredients involved at least one DDI, which was described in Micromedex and/or DIF. Drug Ingredients of 176 involved DDI only described in KFDA drug labeling, but not Micromedex nor DIF. Drug ingredients of 35 which DDIs were described in Micromedex or DIF did not have DDI based on KFDA drug labeling. Micromedex and DIF retrieved 7,582 and 3,071 DDIs, respectively 57.6% and 58.5% of DDIs were also described in KFDA drug labeling. Central nervous system (CNS) drugs, cardiovascular system (CVS) drugs and the antiinfectives appeared to have higher frequency of DDIs among all drug classes. The highest number of DDIs with high severity level ("contraindicated" or "major") were the DDIs of CNS drugs. The antiinfectives are the second drug group having serious DDIs. The DDI pairs of the CNS drug and the antiinfective had the highest contraindication risk (13.6%). DDI information from Micromedex and DIF were not consistent with the result that only 465 ingredients' DDIs are common in both literature (total DDI numbers were 715 vs 488, respectively). And 1,652 DDI information are common in both references among 7,582 vs 3,071 DDIs, respectively. Only 55.2% of DDI information in the database contained in the KFDA drug labeling. Prescribers and pharmacists should pay attention to the drugs for CV system, CNS and infections because of higher risk of possible DDIs compared to other drug classes. KFDA drug labeling is not likely to be recommended as a good information source for DDI due to significant inconsistency of information. Drug information providers should be aware that DDI information from different sources are not consistent and therefore multiple references should be used.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 1998.06a
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• pp.5-28
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• 1998

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.44-50
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• 2020

Background: Drug-drug interactions (DDIs) in patients using oral anticancer treatment are more common than in those using injectable anticancer agents. In addition, DDIs related to anticancer treatment are known to cause clinically significant outcomes, such as treatment failure and severe toxicity. To prevent these negative outcomes, significant DDIs are monitored and managed using the information provided in drug databases. We aimed to evaluate the consistency of information on clinically significant DDIs for tyrosine kinase inhibitors (TKIs) between representative drug databases. Methods: We selected clinically significant DDIs involving medications that are co-prescribed with TKIs and met the following criteria: the severity level of DDIs was equal or greater than "D" in Lexicomp^® or "major" in Micromedex^®. We then analyzed the consistency of the severity classification and evidence level between the drug databases. Spearman's correlation coefficient was used to identify the relationship between DDI information in the drug databases. Results: In total, 627 DDI pairs were identified as clinically significant; information on these was provided by Lexicomp^® and Micromedex^® for 571 and 438 pairs, respectively, and both drug databases provided information on 382 DDI pairs. There was no correlation between the severity and evidence level of DDIs provided in the two databases; Spearman's correlation coefficient for Lexicomp^® and Micromedex^® was -0.009 (p=0.861) and -0.064 (p=0.209), respectively. Conclusion: To judge the significance of DDIs, healthcare providers should consider that the information on DDIs may be different between drug information databases; hence, clinical factors must be considered concurrently.

• 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.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.188-193
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• 2018

Background: Previous studies have noted that the simultaneous use of sulfonylureas and antimicrobials, which is common, could increase the risk of hypoglycemia. In particular, an age of 65 years or older is a known risk factor for sulfonylurea-related hypoglycemia in hospitalized patients. Therefore, we performed this study to determine the potential risk of hypoglycemia from the concurrent use of antimicrobials and sulfonylureas. Methods: We performed a cross-sectional study on the National Health Insurance Service-National Sample Cohort from 2013. The eligibility criteria included patients of 65 years of age or older taking a sulfonylurea with 25 different antimicrobials. Different risk ratings of severity in drug-drug interactions (potential DDIs), level X, D, or C in Lexi-$Interact^{TM}$ online, and contraindicated, major, or moderate severity level in $Micromedex^{(R)}$ were included. SAS version 9.4 was used for data analysis. Results: A total of 6,006 elderly patients with 25,613 prescriptions were included. The largest age group was 70 to 74 (32.7%), and 39.7% of patients were men. The mean number of prescriptions was 4.3 per patient. The most frequently used antimicrobials were levofloxacin (6,583, 25.7%), ofloxacin (6,549, 25.6%), fluconazole (4,678, 18.0%), and ciprofloxacin (2,551, 9.8%). Among sulfonylureas, glimepiride was prescribed most frequently, followed by gliclazide, glibenclamide, and glipizide. Conclusion: Of the antimicrobials with a high potential of hypoglycemia, levofloxacin, ofloxacin, fluconazole, and ciprofloxacin were used frequently. Thus, the monitoring of clinically relevant interactions is required for patients concurrently administered sulfonylureas and antimicrobials.

• Korean Journal of Clinical Pharmacy
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• v.33 no.2
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• pp.122-127
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• 2023

Background: This study was aimed to identify the safety signals of metoclopramide in Korea Adverse Event Reporting System (KAERS) database by proportionality analysis methods. Methods: The study was conducted using Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) reported from January 2013 to December 2017 through KAERS. Signals of metoclopramide that satisfied the data-mining indices of proportional reporting ratio (PRR), reporting odds ratio (ROR) and information component (IC) were defined. The detected signals were checked whether they included in drug labels in the Ministry of Food and Drug Safety (MFDS), U.S. Food and Drug Administration (FDA) and Micromedex^®. Results: A total number of drug AE reports associated with all drugs of data in this study was 2,665,429. Among them, the number of AE reports associated with metoclopramide was 22,583. Forty-two meaningful signals of metoclopramide were detected that satisfied with the criteria of data-mining indicies. Especially neurological signals including extrapyramidal reactions, represented in the safety letter of regulatory agencies were identified in this study. Conclusion: Neurological signals of metoclopramide including extrapyramidal reactions were detected. It is believed that this search for signals can contribute to ensuring safety in the use of metoclopramide.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.220-227
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• 2012

Kidney and liver are the major organs of metabolism and excretion of drugs. Renal and Hepatic impairment may affect the pharmacokinetics/pharmacodynamics and the safety of drugs. Adjusting the dosage based on organ function is the essential role of pharmacists. However, differences have been noted on the recommended dosage among the literatures. We compared and analyzed the recommendations of 4 literature sources which are commonly used for dosage adjustment. From April, 2011 to August, 2011, we selected data on recommendations for dosage adjustment for impaired renal and hepatic function of 100 drugs through a protocol. We analyzed the definition terms of renal and hepatic impairment, recommendations for dosage adjustment, evidenced references in four literature sources: Korean National Formulary (KNF), American Hospital Formulary System Drug Information (AHFS), Micromedex (MM) and Drug Prescribing of Renal Failure (DPRF). We further examined the data homogeneity by comparing how drugs that required no adjustment according to one source were categorized by the other. Sources use different definition terms among themselves except DRPF. Presence or absence of evidenced references about renal/hepatic functional states are KNF (0%/0%), AHFS (78%/62.6%), MM (87.5%/65.6%) and DPRF (93.2%/no recommendation) respectively. Recommendations of specific dosage and dosing interval are KNF (24%/13%), AHFS (39.6%/12.1%), MM (50%/17.7%), and DPRF (55.4%/no recommendation) respectively. Regarding the data homogeneity, the differences were remarkable. Drugs with no adjustment according to AHFS were categorized to be adjusted/ contraindicated by KNF, MM, DPRF and the values were (44%/5.6%), (22%/0%), and (36%/0%) in renal function, (39%/6.5%), (19%/3.2%), and (no recommendation/no recommendation) in hepatic function respectively. Our study shows remarkable definite variation in definitions and recommendations about definition terms, information of dosage and interval, presence or absence of evidenced references. Especially for KNF, quantitative recommendations on dosages and dosing intervals should be made in the near future. To maximize the drug effect and safety and to minimize the heterogeneity of the literature sources, reviewing at least two sources are suggested when recommending the proper dosage adjustment based on organ function.

• Korean Journal of Clinical Pharmacy
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• v.23 no.1
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• pp.42-48
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• 2013

Background: Patients diagnosed with cancer tend to have multiple risk factors for drug related problems such as old age, comorbid conditions, self-medication, additional medications for supportive therapy, and the cancer treatment itself. Objective: The aim of this study was to investigate notable polypharmacy and related problems in oncology patients during hospitalization or following clinic visit. Method: The electronic medical records of patients who were discharged from oncology division at Seoul National University Hospital (SNUH) from June $1^{st}$ to June $30^{th}$, 2011 were retrospectively reviewed. Results: A total of 334 discharged patients were included in this study. Among them, 221 patients had pre-admission medications. Forty percent of the patients, including 60.3% of elderly patients (over 65 years of age) were prescribed more than 5 kinds of medications. Twenty percent of the patients were prescribed to take medications more than 7 times a day. Medication duplications were observed in 2.4% of patients. In 10.5% of the reviewed patients, 47 cases of potential drug-drug interaction including 3 cases of contraindication and 17 cases of major clinical implication according to Micromedex were detected. Medication changes were made in 88% of patients during hospitalization and in 94.7% of patients at their first visit after discharge. Antidiarrheal agent (loperamide) was prescribed along with laxatives in 18.5% of the prescriptions and inadequate instructions on how to take it were observed in 63% of the prescriptions. Conclusion: This study identified the prevalence of polypharmacy and related problems in cancer patients, which presents the need for an active role of pharmacists in pharmaceutical care in oncology wards.