Profiles and Outcomes of Skin Injuries Caused by Injectable Drug Extravasation: An Analysis of the Japanese Adverse Drug Event Report Database.

Extravasation occurs when injectable drugs leak out of the blood vessels, damaging the surrounding tissues and causing a variety of skin injuries. This study aimed to comprehensively analyze extravasation risk, skin injury profiles, and outcomes for suspect drugs from the Japanese Adverse Drug Event Report (JADER) database. Adverse events were defined according to the Medical Dictionary for Regulatory Activities/Japanese version; the term extravasation (Standardized MedDRA Query Code: 20000136) was used in this analysis. The names of adverse events were entered as unified preferred terms and redefined to evaluate skin injury profiles. In addition, skin injury outcomes were divided into 2 broad categories: "improvement" and "no improvement." Reporting odds ratios were used to detect signals for adverse events. A total of 656 cases of extravasation-related adverse events were reported between April 2004 and January 2022. Signals for extravasation-related adverse events were detected from 11 drugs. Then, their respective skin injury profiles and outcomes were determined. These results suggest a relationship between adverse events associated with extravasation and 11 drugs and identify the characteristics of each skin injury and their outcomes. These findings will contribute to improving the quality of infusion management in clinical practice.

Promoting generic drug usage in Japan: correlation between generic drug usage and monthly personal income.

BACKGROUND: To reduce pharmacy-related medical expenses, it is necessary to cut drug costs, potentially by increasing generic drug usage. This study analyzes the correlation between generic drug usage and monthly personal income by examining prescriptions for individual drugs. METHODS: We conducted a cross-sectional study based on the data set from the National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data Japan and the Basic Survey on Wage Structure. We calculated the correlation coefficient between the usage rate of generic drugs in each prefecture of Japan and monthly personal incomes. We then analyzed the correlation coefficients based on the therapeutic categories of medicinal drugs; the contingency table was visualized as a mosaic plot. To compare the proportions between multiple categories, the chi-squared test was applied as a statistical significance test that was used in the analysis of n × m contingency tables. We worked with the null hypothesis that there were no differences between classes in the population. RESULTS: Regarding the correlation coefficient between the usage rate of generic drugs and monthly personal incomes, the proportion of negative correlation coefficients for outpatient out-of-hospital and outpatient in-hospital prescriptions was over 70%, while that for inpatient prescriptions was 46.9%. The proportion of medicinal drugs exhibiting a negative correlation between the rates of generic drug usage and monthly personal incomes for outpatient out-of-hospital prescriptions and outpatient in-hospital prescriptions was higher than that of inpatient prescriptions. The proportion of statistically correlated medicinal drugs among inpatient prescriptions was lower than that among outpatient out-of-hospital and outpatient in-hospital prescriptions. The proportions of significant negative correlations for outpatient out-of-hospital, outpatient in-hospital, and inpatient prescriptions were 30.6%, 22.7%, and 3.5%, respectively. It was also observed that the rate of generic prescription usage for outpatient out-of-hospital and in-hospital prescriptions increased as monthly personal incomes decreased. In outpatients, the therapeutic categories with strong negative correlations were vasodilators and hyperlipidemia drugs. CONCLUSIONS: Our results may help to increase the usage rate of generic drugs in different prefectures by providing useful information for promoting them throughout Japan.

Analysis of drug-induced hand-foot syndrome using a spontaneous reporting system database.

Purpose: The aim of our study was to assess the clinical features of hand-foot syndrome (HFS) associated with certain systemic chemotherapeutic drugs in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database. Methods: HFS was defined using the preferred terms from the Medical Dictionary for Regulatory Activities. We used several indices, such as the reporting odds ratios (RORs) at 95% confidence interval (CI), the time-to-onset profile of HFS, and cluster analysis. Results: Of 646,779 reports (submission period: April 2004 to September 2020), 1814 reported HFS events. The RORs (95% CI) for axitinib, capecitabine, lapatinib, regorafenib, sorafenib, and sunitinib were 14.9 (11.1-20.1), 54.6 (49.2-60.6), 130.4 (110.7-153.6), 63.3 (55.2-72.6), 29.0 (25.8-32.7), and 13.9 (11.7-16.5), respectively. The analysis of time-to-onset profiles revealed that the median values (interquartile range: 25.0-75.0%) of drug-induced HFS caused by capecitabine, cisplatin, docetaxel, everolimus, regorafenib, sorafenib, and trastuzumab were 21.0 (13.0-42.0), 15.0 (10.0-82.0), 6.0 (3.0-25.0), 86.5 (67.0-90.5), 9.0 (6.0-14.0), 9.0 (6.0-14.0), and 70.0 (15.0-189.0) days, respectively. The number of clusters was set to 4. Among these, one cluster, which included capecitabine, regorafenib, and lapatinib, exhibited a higher reporting ratio and ROR of drug-induced HFS than other drugs. Conclusions: The RORs and results of time-to-onset analysis obtained in this study indicated the potential risk of HFS associated with chemotherapeutic drugs. Our results suggest that health care professionals must be aware of the potential onset of drug-induced HFS with docetaxel, regorafenib, and sorafenib for at least 4 weeks; therefore, careful observation is recommended. Plain Language Summary: Elucidation of the relationship between cancer drugs and risk of hand-foot syndrome: Purpose: Hand-foot syndrome (HFS) is an adverse effect of some cancer drugs, which is characterized by symptoms such as redness, swelling, blistering, and pain in the area of palms and soles. HFS reduces the quality of life of patients and can sometimes interfere with anticancer treatment plans. It is important to understand the clinical manifestations of HFS and gain knowledge that will allow for early intervention by clinicians.Methods: In this study, we used a large-scale side effect database of real-world cases for a comprehensive investigation of anticancer-drug-induced HFS. The database contained 646,779 adverse event reports from April 2004 to September 2020; among which, we identified 1814 HFS events. Using these data, we could obtain information on the relationship between 19 types of anticancer drugs and HFS, and the onset time of HFS and HFS prognosis related to each anticancer drug. Results: Our results suggest that clinicians should monitor the risk of HFS with docetaxel, regorafenib, and sorafenib for at least the first 4 weeks after drug administration. Conclusion: These findings are crucial for improving the management of the adverse effects caused by anticancer drugs.

Analysis of chemotherapy-induced peripheral neuropathy using the Japanese Adverse Drug Event Report database.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event associated with several antineoplastic drugs; however, the precise risks and time course of reactions of particular drugs are not clearly understood. The aim of this study was to evaluate the relationship between anticancer agents and CIPN development using data from the Japanese Adverse Drug Event Report (JADER) database and to characterize the time-to-onset and outcomes of CIPN. Chemotherapy-induced peripheral neuropathy was defined using the Medical Dictionary for Regulatory Activities preferred terms. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence interval for signal detection. Data of nine Anatomical Therapeutic Chemical (ATC) drug categories correlated with CIPN development, in addition to the data of the time-to-onset and outcomes. Among 622,289 reports in the JADER database from April 2004 to March 2020, there were 1883 reports of adverse events corresponding to peripheral neuropathy. The ROR (95% confidence interval) for vinblastine, sorbent-based paclitaxel (sb-PTX), oxaliplatin, and bortezomib was 20.4 (12.5-33.4), 13.6 (11.9-15.7), 26.2 (23.6-29.1), and 30.8 (26.6-35.8), respectively. The median duration (interquartile range) to CIPN development after the administration of vinca alkaloids and analogues, taxanes, platinum compounds, and monoclonal antibodies was 11.0 (5.0-46.5), 22.5 (6.0-82.5), 22.0 (6.0-68.5), and 32.5 (11.3-73.8) days, respectively. The median duration (interquartile range) of sb-PTX and nanoparticle albumin-bound (nab)-PTX was 35.0 (7.0-94.0) and 5.5 (3.0-29.3) days, respectively. Our analysis of records in the JADER database revealed several drugs associated with a high risk for CIPN development. In particular, the development of CIPN after vinca alkaloid administration should be closely monitored for 2 weeks after administration. CIPN caused by nab-PTX showed significantly faster onset than that by sb-PTX. Patients who receive taxanes or monoclonal antibodies often do not show an improvement; accordingly, early treatment is required.

Assessment of Reye's syndrome profile with data from the US Food and Drug Administration Adverse Event Reporting System and the Japanese Adverse Drug Event Report databases using the disproportionality analysis.

OBJECTIVES: Reye's syndrome is a rare and potentially fatal illness that is defined as encephalopathy accompanied by liver failure. The aim of this study was to assess Reye's syndrome profiles by analyzing data from the spontaneous reporting system database. METHODS: We analyzed reports of Reye's syndrome using the US Food and Drug Administration Adverse Event Reporting System and the Japanese Adverse Drug Event Report databases. The reporting odds ratio and proportional reporting rate were used to detect the pharmacovigilance signal. RESULTS: The US Food and Drug Administration Adverse Event Reporting System contains 12,201,620 reports from January 2004 to June 2020, of which 186 are on Reye's syndrome. The Japanese Adverse Drug Event Report contains 646,779 reports from April 2004 to September 2020, of which 30 are on Reye's syndrome. In the US Food and Drug Administration Adverse Event Reporting System database, the reporting odds ratios (95% confidence interval, number of cases) of aspirin, diclofenac, ibuprofen, acetaminophen, and valproate sodium were 404.6 (302.6-541.0, n = 80), 15.1 (6.7-34.1, n = 6), 26.2 (16.1-42.6, n = 18), 10.7 (5.5-20.9, n = 9), and 47.1 (26.2-84.6, n = 12), respectively. In the Japanese Adverse Drug Event Report database, the reporting odds ratios (95% confidence interval, number of cases) of aspirin, diclofenac, ibuprofen, loxoprofen, acetaminophen, and valproate sodium were 14.1 (5.4-36.8, n = 5), 51.7 (22.2-120.5, n = 7), 135.0 (40.8-446.2, n = 3), 17.6 (6.7-46.0, n = 5), 24.0 (9.2-62.6, n = 5), and 13.8 (3.3-57.9, n = 2), respectively. The reported number of female patients aged 30-39 years was the highest in the Japanese Adverse Drug Event Report. CONCLUSION: Although the frequency of the occurrence of Reye's syndrome is low, the possible risk of the disease occurring in adult females should be considered.

Trends Associated with Hemorrhoids in Japan: Data Mining of Medical Information Datasets and the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data Japan.

Hemorrhoids are a common anorectal disease. Epidemiological studies on medication trends and risk factors using information from real-world databases are rare. Our objective was to analyze the relationship between hemorrhoid treatment prescription trends and several risk factors using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data Japan and related medical information datasets. We calculated the standardized prescription ratio (SPR) based on the 2nd NDB Open Data Japan from 2015. The correlation coefficients between the SPR of antihemorrhoidals and those of "antispasmodics," "antiarrhythmic agents," "antidiarrheals, intestinal regulators," "purgatives and clysters," "hypnotics and sedatives, antianxietics," "psychotropic agents," and "opium alkaloids preparations" were 0.7474, 0.7366, 0.7184, 0.6501, 0.6320, 0.4571, and 0.4542, respectively. The correlation coefficient between the SPR of antihemorrhoidals and those of "average annual temperature," "percentage of people who were smokers," and "percentage of people who drank regularly" were -0.7204, 0.6002, and 0.3537, respectively. The results of cluster analysis revealed that Hokkaido and Tohoku regions tended to have low average annual temperature values and high percentage of people who were smokers and had comparatively high SPRs of "antispasmodics," "antiarrhythmic agents," "antidiarrheals, intestinal regulators," "purgatives and clysters," "hypnotics and sedatives, antianxietics," "psychotropic agents," and "opium alkaloids preparations." Antihemorrhoidals are frequently used in Hokkaido and Tohoku, Japan; thus, it is important for these prefectural governments to focus on these factors when taking measures regarding health promotion.

Analysis of immune-related adverse events caused by immune checkpoint inhibitors using the Japanese Adverse Drug Event Report database.

PURPOSE: The aim of our study was to characterize the clinical features of immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) in a real-world setting using the Japanese Adverse Drug Event Report (JADER) database. METHODS: The irAEs were defined using the preferred terms of the Medical Dictionary for Regulatory Activities. irAEs were categorized as follows: adrenal insufficiency, colitis, eye diseases, hematological disorder, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia gravis, myocarditis, nephritis/renal dysfunction, pneumonitis, rash, and type 1 diabetes mellitus. We used several indices such as reporting odds ratio (ROR) to assess disproportionality in pharmacovigilance data, time-to-onset analysis using Weibull shape parameters, and the association rule mining technique to evaluate possible risk factors between variables in the spontaneous reporting system database. RESULTS: The JADER database contained 534 688 reports from April 2004 to June 2018. The RORs of pneumonitis including interstitial lung disease for nivolumab, pembrolizumab, and ipilimumab were 7.02 (95% confidence interval: 6.55-7.52), 9.08 (8.28-9.97), and 1.74 (1.27-2.38), respectively. The median onsets (quartiles, 25-75%) of myocarditis caused by nivolumab and pembrolizumab were 28.0 (15.5-60.5) and 18.0 (13.0-44.5) days, respectively. Co-therapy with nivolumab and ipilimumab may be associated with irAEs in several categories as per the association rule mining analysis. CONCLUSION: Our results demonstrated a potential risk of irAEs associated with ICIs, based on RORs and time-to-onset analysis. Furthermore, our findings indicated that patients receiving nivolumab and ipilimumab as co-therapy should be carefully monitored.