• Journal of Korean Society of Health-System Pharmacists
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• v.35 no.4
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• pp.430-440
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• 2018

Background : Hyponatremia is the most common electrolyte disturbance in hospitalized patients and has been associated with increased morbidity and mortality. Tolvaptan, a vasopressin receptor antagonist, is increasingly used for the treatment of euvolemic and hypervolemic hyponatremia. The aim of this study was to evaluate the effectiveness and safety of tolvaptan for the management of hyponatremia. Methods : This study was a retrospective evaluation of 106 patients who received at least one dose of tolvaptan for hyponatremia at a single tertiary academic hospital between January 2014 and June 2015. The primary endpoint was the change in serum sodium concentration after tolvaptan administration within 24 hours, with secondary endpoints of overcorrection and adverse effects. Results : The mean initial dose of tolvaptan was $20.2{\pm}7.2mg$ and the median duration of treatment was 15 days (range, 1-261 days). The maximal changes in sodium levels at 24 and 48 hours were $8.2{\pm}4.7mmol/L$ and $10.5{\pm}15.3mmol/L$, respectively. Of 99 patients in whom sodium concentrations were followed up, sodium overcorrection was observed in 26 (26.3%) patients, which was associated with concomitant use of an enzyme inhibitor (odds ratio [OR] = 4.80, 95% Cl: 1.27-18.15). However, sex, body mass index (BMI), serum albumin, a daily dose of tolvaptan, and concomitant use of hypertonic saline did not show any significant difference in overcorrection. The most commonly reported adverse effects were mild and related to aquaresis, such as polyuria, thirst, and constipation. However, severe adverse effects such as hyperkalemia, hypotension, and one death related to osmotic demyelination were also reported. Conclusions : Tolvaptan is effective for treating hyponatremia. Nevertheless, the drug should be used cautiously due to serious adverse effects related to sodium overcorrection.

• 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.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.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.323-323
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• 2001

• 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.

• Quality Improvement in Health Care
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• v.2 no.1
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• pp.86-109
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• 1995

Clinical trials of drugs on humans is the final and most important stage in evaluating the safety and efficacy of the drugs. Good Clinical Practice(GCP) standards were announced in 1987 to protect testees' rights as well as to ensure validity of the clinical trial results, but its implementation has been delayed until now. The purpose of this study is to evaluate the preparedness of the designated institutions to abide by GCP standards during clinical trials, and thereby to determine GCP implementability at the institutions. Survey on the status of clinical trials was conducted for the designated 83 clinical trial hospitals. Response rate was 95.2%. Donabedian's quality assessment model was applied as the basic framework for the study. And the relative - weights for the evaluation items were determined by expert's evaluation. Among the designated 83 hospitals, 39 conducted clinical trials to obtain drug manufacturing approval from 1990 to 1994. Only 19 institutions are found to be able to meet the requirements of KGCP. Structure variables - manpower, organization, and facility -, which are the basic elements for GCP, are evaluated as unsatisfied in many hospitals. Institutions which established IRB 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 institutions, respectively. Also, the institutions providing educational programs on conducting clinical trials are few - 20. The study results indicates that the level of conducting KGCP is unsatisfactory. However, more institutions are expected to be able to meet the standards soon because GCP standards does not require so much regulation on facilities, but stress importance on research methodology and human right. At present as the institutions for clinical trials are primarily training hospitals with residency programs, such efforts as education will accelerate the implementability of GCP in Korea. Institutions must build the appropriate infrastructure and government must prepare to strongly enforce KGCP before it can successfully take place.