• Korean Journal of Clinical Pharmacy
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• v.25 no.1
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• pp.56-58
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• 2015

Summary: We report the first hepatic adverse effect of tosufloxacin tosylate in a muscle invasive bladder cancer patient with normal liver functions and with scheduling to undergo a surgical operation for a neobladder. Tosufloxacin tosylate 150 mg was administered to a 57-year-old man who maintained transurethral resection of bladder tumor (TUR-BT) postoperative multiple medications. His labs presented significant increases in alanine amino transferase (ALT) and aspartate amino transferase (AST) levels with 2-week compliance of 150 mg tablet three times a day. After discontinuing tosufloxacin tosylate, the levels slowly decreased and completely returned to normal ranges without any intervention in a few weeks. The Naranjo Causality Algorithm indicates a probable relationship between increased ALT and tosufloxacin. The patient was to have the second surgical operation as scheduled after getting normal range of ATL level. Therefore, tosufloxacin should be avoided in patients at risk for having liver dysfunctions or diseases if the patients have a schedule for any operation. Background: Tosufloxacin tosylate has been shown to have favorable benefits as an antibiotic. Tosufloxacin tosylate may be considered to have the adverse effects such as nauseas, vomiting, diarrhea, abdominal pain, stomatitis, tendonitis, tendon rupture, headache, dizziness, drowsiness, insomnia, weakness, agitation including hemolysis in the event of glucose-6-phosphate dehydrogenase deficiency as other fluoroquinolones. More severe adverse reactions of tosufloxacin tosylate over the above common adverse effects of fluoroquinolones were thrombocytopenia and nephritis. It also is not well known that tosufloxacin can cause hepatic problem. Here the study reports the first hepatic reaction from tosufloxacin and might arouse heath care providers' attention to appropriate drug choice for patients.

• Journal of Sasang Constitutional Medicine
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• v.19 no.3
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• pp.277-282
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• 2007

1. Objectives This paper reports a case of cervical cancer patient who showed positive results to Sasang Constitutional Medicine. The target symptoms were urinary disorder due to unilateral hydronephrosis and urticaria due to adverse drug reactions. 2. Methods We measured urinary output and interval. We evaluated skin urticaria by severity and size of itchy site. The patient treated using Sasang Constitutional Medicine. 3. Results and Conclusions Significant improvement was observed in urinary output and interval.

• Korean Journal of Clinical Pharmacy
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• v.22 no.4
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• pp.340-346
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• 2012

Background: Amphotericin B is a mainstay in the treatment of many systemic fungal infections due to its wide antifungal spectrum and low incidence of resistance. However, the use of amphotericin B is limited by its nephrotoxicity. Objectives: The objective of this study was to evaluate the incidence and risk factors of renal adverse drug reactions (ADRs) of conventional amphotericin B (Fungizone$^{(R)}$). In addition, we compared the changes of serum creatinine (SCr) between patients who remained conventional amphotericin B and patients who were switched to liposomal amphotericin B after occurrence of renal adverse reactions. Methods: Adult hospitalized patients who reported renal adverse reactions caused by conventional amphotericin B from January 2011 to July 2012 at pharmacovigilance center in Yonsei University Healthcare System included in this study. ADRs scored as 'doubtful' in Naranjo probability ADR scale were excluded. We retrospectively analyzed patients' basic clinical characteristics, concurrent diseases or nephrotoxic drugs in order to find variables that can correlate with occurrence of renal ADRs. Changes in SCr were compared between conventional amphotericin B group and liposomal amphotericin B group. Results: A total of 231 ADRs after administration of conventional amphotericin B in 75 patients were reported to pharmacovigilance center and assessed their severities as 'possible', 'probable', or 'definite'. Renal adverse reaction was the most common ADR with incidence rate of 42% (96 of 231 ADRs). Mean change in SCr from baseline was 0.26 mg/dL (change % 37.8) and statistically significant (p=0.000). Simple correlations analysis revealed that the number of concurrent diseases and number of nephrotoxic drugs were positively correlated with changes in SCr, but these results were not statistically significant. Among 43 patients who remained amphotericin B after occurrence of renal ADRs, 27 patients was administered conventional amphotericin B and 16 patients changed to liposomal amphotericin B. Mean change in SCr in amphotericin B group was 0.23 mg/dL (32.75%), whereas mean change in SCr in liposomal amphotericin B group were -0.28 mg/dL (19.38%) and difference between two groups was statistically significant (p=0.003). The numbers of patient with SCr elevation more than 30% were 9 (33.3%) in amphotericin B group and 2 (12.5%) in liposomal amphotericin B group (Odd Ratio=3.50, 95% Confidence Interval 0.65-18.85; p=0.130). Conclusion: An analysis of ADRs due to amphotericin B administration revealed significant mean changes in SCr from baseline. Switching to liposomal amphotericin B showed significant decrease in SCr compared with conventional amphotericin B.

• Korean Journal of Clinical Pharmacy
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• v.19 no.2
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• pp.120-130
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• 2009

The objective of this study was to analyze and to improve therapeutic drug monitoring(TDM) service of vancomycin in a local hospital. Patients with TDM service between September 2005 and December 2008 were included and the data were collected for vancomycin use and components of TDM. During that period, 421 cases of TDM service of vancomycin in 236 patients were retrospectively reviewed. The first dosages of vancomycin were appropriate in 135(57.2%) patients and administration of vancomycin was discontinued in 126(53.4%) patients due to therapeutic failure or adverse drug reaction. MRSA was identified in 191(80.9%) patients and 135(70.7%) samples for the identification were sputum. According to the TDM reports, 232(55.1%) serum samples were obtained at the steady-state conditions and 55.5% of the samples that were drawn before the steady-state was due to the physician's inappropriate knowledge about the steady-state. Based on the time of vancomycin administration, 35.8% of the samples were not obtained at the recommended sampling time. For the patients in general wards, the most common reason for the incorrect samples was routine serum sampling by the laboratory medicine phlebotomists between 6 and 8 a.m. except sunday. In contrast, samples drawn by nurses or physicians at inappropriate time were the most common reason for the incorrect samples with patients in the intensive care units. Physicians accepted 68.5% of the recommendations for vancomycin dosage and administration. In conclusion, TDM service of vancomycin needs to be improved in inappropriate sampling time and vancomycin dosage. For solving these problems, current team made of TDM pharmacists and physicians of laboratory medicine can be expanded to include a physician of infectious diseases, nurses and laboratory medicine phlebotomists as new members. Through the TDM service of vancomycin by the new team, we can settle the problems and make the guideline for the scientific controversies associated with therapeutic monitoring of vancomycin.

• Tuberculosis and Respiratory Diseases
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• v.73 no.4
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• pp.231-233
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• 2012

Tadalafil is a phosphodiesterase-5 inhibitor (PDE5I), which is widely used to treat erectile dysfunction. Although PDE5Is have excellent safety profiles, and most of the side effects are mild, rare serious adverse events have been reported in association with PDE5Is. Thrombosis is one of those events, and a few previous reports have suggested the association of PDE5Is with thrombosis. We report the case of a 61-year-old male who developed pulmonary embolism combined with pulmonary infarction directly after taking tadalafil. Both the patient and the physician suspected tadalafil as the culprit drug, as the patient was in an otherwise healthy condition. However, after extensive evaluation, we noticed that factor VIII levels were elevated. Prior reports suggesting the association between thrombosis and PDEIs either lack complete information on coagulation factors, or show inconsistencies in their results. Physicians should operate caution prior to accepting the diagnosis of adverse drug reaction.

• Korean Journal of Clinical Pharmacy
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• v.5 no.2
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• pp.33-49
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• 1995

The purpose of this study is to understand present situation of clinical trials, and evaluate the preparedness of the desiRnated institutions to abide by GCP(Good Clinical Practice) standards during clinical trials. Survey on the status of clinical trials was conducted for the desienated 83 clinical trial hospitals, and response rate was $95.2\%$. The results showed that 39 hospitals have conducted clinical trials to obtain drug manufacturing approval from 1990 to 1994. Most of them were trials on Phase III. Only $46.8\%$ of the institutions had sufficient human resources to perform the clinical trials. Institutions which established IRB(Institutional Review Board) accounted for 41 or $51.9\%$, but those who have a protocol evaluation guideline, or Adverse Drug Reaction(ADR) reporting system were only 12, and 21 Places, respectively. Regarding supervision of the investigational drugs, less than 30 institutions designated pharmacist as a supervisor. In conducting clinical trials, $97.4\%$ of trials had high rates of prior consent of testees, but only part of them-$61.7\%$-gave written consent. The level of conducting GCP is found to be unsatisfactory. Institutions must build the appropriate infrastructure and government must prepare in order to protect testees' rights as well as to ensure validity of the results.

• The Journal of Internal Korean Medicine
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• v.30 no.1
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• pp.144-152
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• 2009

Background : Ephedra (Ephedra sinica) has been widely used to treat respiratory disease in traditional medicine of East Asia for over a hundred years. Despite safety concerns raised by some, the use of ephedra in traditional medicine is documented over more than 1,800 years. It is well established that ephedra is one of the central medicines in Korean 'Seseng constitution' medicine. In Sasang constitution medicine, all humans can be divided into one of four types: Soeumin, Soyangin, Taeumin or Taeyangin, and each constitution type has their own typical characteristics. Accordingly, it is hypothesized that the adverse effects of ephedra differ depending on the Sasang constitution classification. Objectives : The aim of this study was to determine adverse effects of ephedra which is classified as a Taeumin herb, and to observe whether the response differs or not. according to Sasang constitution classification. Methods : The study design was a double-blind randomized controlled trial. The subjects were healthy adults 20 - 50 years old who agreed to participate in this study. They were allocated through randomization to either ephedra group (N=55) or placebo group (N=24). where ephedra extract (6 g of dried ephedra) and placebo with similar opaque capsules were given twice for one day. To compare the adverse events of ephedra according to Sasang constitution classification, we analyzed blood pressure (systolic and diastolic), pulse rate, the morning questionnaire, and patient's global assessment scale score for well known adverse events: palpitation, headache, sweating, tiredness, dyspepsia, and dry mouth. Results : After ingestion of ephedra, the pulse rate had a significant increase in all constitution types. The changes of diastolic pressure in Soeumin and the changes of pulse rate in Soeumin, Soyangin and Taeumin had a significant increase in the ephedra over the control group. In the ephedra group, the palpitation and dyspepsia score of the patients' global assessment scale had a significant increase in Soeumin, with palpitation and sweating score increasing in Soyangin. Others observations were insignificant results. Conclusion : The results of this study may confirm that the physical responses or adverse effects of herbs differ for each type of Sasang constitution. Future studies using other herbs will be required to ascertain the herbal drug reaction of Sasang constitutions.

• Korean Journal of Clinical Pharmacy
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• v.22 no.3
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• pp.251-259
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• 2012

Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Use of biological therapies may reduce or delay the surgical procedures in patients with UC. The aim of this study was to determine the impact of infliximab (IFX) use on the rate of remission, surgical interventions, and the effect on quality of life in patients with moderate to severe UC. Literature was searched for studies that investigated the efficacy of IFX on the rate of remission, colectomy and quality of life (QoL) between January 1990 and June 2012 at MEDLINE, January 1988 and June 2012 at EMbase and others. Eleven trials were included in the meta-analysis; divided into placebo controlled 8 trials and intravenous corticosteroid controlled group 3 trials. In comparison to placebo control groups, patients who received IFX had an odds ratio (OR) of 3.712 (95% CI: 2.714, 5.079) for the short-term clinical remission, and 3.053 (95% CI: 2.044, 4.559) for the rate of long-term remission. In colectomy rate and quality of life (QoL), odds ratio were 0.566(95% CI: 0.387, 0.827) and 0.658 (0.505, 0.811) respectively. Any adverse reactions including infections, infusion reaction, rash and arthralgia were equivalent in both groups. Compared with intravenous corticosteroid controlled group, patients who received IFX had lower remission rate with short-term odds ratio 0.227 (95% CI: 0.033, 1.556) and long-term odds ratio 1.054 (95% CI: 0.317, 3.502) respectively. However, statistical significance was not showed with both two analyses. The higher adverse drug reaction (ADR) rates were occurred in the corticosteroid controlled groups. 73.3% of patients treated corticosteroid reported Cushing-like syndrome with moon face. In conclusion, IFX does increase remission rate and decrease the rate of colectomy in patients with UC without elevating any adverse reactions significantly. IFX also improves QoL in moderate to severe UC patients. It would not exceed the efficacy of intravenous corticosteroid, whereas intravenous corticosteroid also reported high rate of adverse reactions.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.63-67
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• 2016

Severe graft-versus-host disease (GVHD) is an often lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT). The safety of clinical-grade mesenchymal stem cells (MSCs) has been validated, but mixed results have been obtained due to heterogeneity of the MSCs. In this phase I study, the safety of bone marrow-derived homogeneous clonal MSCs (cMSCs) isolated by a new subfractionation culturing method was evaluated. cMSCs were produced in a GMP facility and intravenously administered to patients who had refractory GVHD to standard treatment resulting after allogeneic HSCT for hematologic malignancies. After administration of a single dose ($1{\times}10^6cells/kg$), 11 patients were evaluated for cMSC treatment safety and efficacy. During the trial, nine patients had 85 total adverse events and the rate of serious adverse events was 27.3% (3/11 patients). The only one adverse drug reaction related to cMSC administration was grade 2 myalgia in one patient. Treatment response was observed in four patients: one with acute GVHD (partial response) and three with chronic GVHD. The other chronic patients maintained stable disease during the observation period. This study demonstrates single cMSC infusion to have an acceptable safety profile and promising efficacy, suggesting that we can proceed with the next stage of the clinical trial.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.4
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• pp.215-220
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• 2016

Objective: To evaluate the efficacy and safety of dienogest treatment in patients who had received dienogest for 12 months or more to treat endometriosis. Methods: We analyzed the clinical data of 188 women with endometriosis who had been treated with 2 mg of dienogest once a day for 12 months or more at a single institute. We evaluated changes in endometriosis-associated pain and endometrioma size, recurrence rate, and adverse events following dienogest administration. Bone mineral density (BMD) was measured in patients who were prescribed dienogest for more than 18 months. Results: Pain was significantly reduced at 12 months after dienogest medication. In those treated with dienogest due to recurrent endometrioma, the size of the endometrioma was significantly decreased at the 12-month and 18-month follow-ups. We found only one case of sonographic recurrence during dienogest administration among those who were treated postoperatively to prevent recurrence (1 of 114, 0.9%). The most common adverse drug reaction was uterine bleeding (3.2%), and other adverse events were generally tolerable and associated with low discontinuation rates (5.2%). Among the 50 patients in whom BMD was measured, 10 patients (20%) had a Z-score below the expected range for age. Conclusion: The administration of dienogest for a year or more seems to be highly effective in preventing recurrence after surgery, reducing endometriosis-associated pain, and decreasing the size of recurrent endometrioma, with a favorable safety and tolerability profile. However, BMD should be checked in patients on long-term medication due to possible bone loss in some women.