Evaluation of the Expression Profile of Antibiotic-Induced Thrombocytopenia Using the Japanese Adverse Drug Event Report Database

Drug-induced thrombocytopenia (DITP) can be triggered by antibiotics; however, the details remain unclear. Here, we evaluated the expression profiles of DITP using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of DITP between April 2004 and January 2021 from the JADER database. The reporting odds ratio (ROR) and 95% confidence interval (CI) were used to detect DITP signals. Factors thought to affect DITP, such as male sex and an age of at least 60 years, were added as covariates. We evaluated the time-to-onset profile and hazard type using the Weibull shape parameter. The JADER database contained 1,048,576 reports. Twelve of 60 antibiotics showed signals for DITP; the RORs (95% CIs) for ampicillin/sulbactam, ceftazidime, cefozopran, ciprofloxacin, fluconazole, fos-fluconazole, linezolid, pazufloxacin, piperacillin/tazobactam, teicoplanin, trimethoprim/sulfamethoxazole, and voriconazole were 1.75 (1.41-2.16), 1.77 (1.42-2.18), 1.35 (1.06-1.72), 2.56 (2.19-2.98), 1.93 (1.67-2.23), 2.08 (1.76-2.46), 5.29 (2.73-9.60), 1.92 (1.51-2.41), 1.54 (1.05-2.19), 1.47 (1.16-1.84), 1.92 (1.73-2.14), and 2.32 (1.59-3.30), respectively. In multiple logistic regression analysis, 7 and 6 antibiotics were detected for the factors age and male sex, respectively. The median times-to-onset of DITP for ciprofloxacin (oral treatment), fluconazole, linezolid, piperacillin/tazobactam, and trimethoprim/sulfamethoxazole were 91, 91, 11.5, 10, and 9 days, respectively. Furthermore, the 95% CI of the Weibull shape parameter β for these antibiotics was above and excluded 1, indicating that the antibiotics were the wear out failure type. We revealed the expression profiles of DITP following treatment with 12 antibiotics.

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Comprehensive Analysis of Antibiotic-induced Agranulocytosis Using the Japanese Adverse Drug Event Report Database

10.22541/au.161839221.10007524/v1 ◽

2021 ◽

Author(s):

Yuki Asai ◽

Takanori Yamamoto ◽

Yasuharu Abe

Keyword(s):

Confidence Intervals ◽

Adverse Drug Event ◽

Shape Parameter ◽

Comprehensive Analysis ◽

Drug Event ◽

Event Report ◽

Odds Ratios ◽

Drug Induced ◽

Failure Type

Although infrequent, drug-induced agranulocytosis can be stimulated by antibiotics. Here, we analyzed the Japanese Adverse Drug Event Report database to identify profiles of antibiotic-induced agranulocytosis. Ten of 60 antibiotics showed signals for agranulocytosis; the reporting odds ratios (95% confidence intervals) for ampicillin/sulbactam, amikacin, cefmetazole, cefozopran, clindamycin, ciprofloxacin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 2.65 (1.79–3.80), 2.49 (1.91–4.34), 4.48 (2.27–6.92), 2.77 (1.88–3.95), 1.64 (1.04–2.47), 2.01 (1.40–2.82), 2.78 (2.11–3.60), 6.05 (2.16–13.7), 2.05 (1.31–3.07), and 3.54 (2.73–4.54), respectively. The median times-to-onset of agranulocytosis for ampicillin/sulbactam, cefmetazole, cefozopran, clindamycin, imipenem/cilastatin, kanamycin, teicoplanin, and vancomycin were 20, 6, 10, 16, 12, 3, 18, and 13 days, respectively. The 95% confidence intervals of the Weibull shape parameter β for these antibiotics were over and excluded 1, indicating that the antibiotics were the wear out failure type. These findings provided insights into the characteristics of antibiotic-induced agranulocytosis.

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Pharmacovigilance Assessment of Drug-Induced Acute Pancreatitis Using a Spontaneous Reporting Database

International Journal of Toxicology ◽

10.1177/1091581819870717 ◽

2019 ◽

Vol 38 (6) ◽

pp. 487-492 ◽

Cited By ~ 3

Author(s):

Iku Niinomi ◽

Keiko Hosohata ◽

Saki Oyama ◽

Ayaka Inada ◽

Tomohito Wakabayashi ◽

...

Keyword(s):

Acute Pancreatitis ◽

Odds Ratio ◽

Spontaneous Reporting ◽

Adverse Drug Events ◽

Drug Event ◽

Reporting Odds Ratio ◽

Event Report ◽

Disproportionality Analysis ◽

Drug Induced ◽

Spontaneous Reporting Database

Background: Acute pancreatitis (AP) is associated with risks of morbidity and mortality. The incidence of AP recently increased compared to that traditionally reported in the literature. Objective: The purpose of this study was to evaluate the possible association between AP and drugs using the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database of adverse drug events. Methods: Adverse event reports submitted to the JADER database between 2004 and 2017 were analyzed. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence intervals for signal detection. Results: A total of 3,443 reports (0.17% of all adverse events) were identified as drug-induced AP, in which 431 different drugs were involved. Acute pancreatitis was frequently reported in men (58.5%) in their 60s (19.1%); 40.6% developed AP within 4 weeks after the treatment. Among the most frequently reported drugs, signals were detected for prednisolone, ribavirin, sitagliptin, mesalazine, tacrolimus, and l-asparaginase, which are well-known causes of AP. Telaprevir, donepezil, and ustekinumab also generated signals. As for drugs with high RORs, l-asparaginase and alogliptin were noteworthy. Conclusion: Most of the identified drugs were already known to induce AP, but the likelihood of the reporting of AP varied among the drugs. Our results should raise physicians’ awareness of drugs associated with AP, but further investigation of these medications is warranted.

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Analysis of patients with hypomagnesemia using the Japanese Adverse Drug Event Report database (JADER)

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps29692 ◽

2018 ◽

Vol 21 ◽

pp. 46-53 ◽

Cited By ~ 2

Author(s):

Hiroyuki Tanaka ◽

Yuka Yoshiba ◽

Tomoko Watanabe ◽

Mitsutoshi Satoh ◽

Toshihiro Ishii

Keyword(s):

Adverse Events ◽

Adverse Drug Event ◽

Antitumor Agent ◽

Drug Event ◽

Reporting Odds Ratio ◽

Event Report ◽

Drug Involvement ◽

Large Peak ◽

Egfr Antibody ◽

Electrolyte Abnormalities

Summary – Purpose. In order to clarify the occurrence of hypomagnesemia in Japan, we conducted a database search and analysis using the Japanese Adverse Drug Event Report database (JADER). Methods. Among the cases recorded in JADER between April 2004 and December 2015, we targeted “hypomagnesemia” and analyzed the patients’ backgrounds, drug involvement, other adverse events reported with hypomagnesemia, the time of hypomagnesemia onset, outcomes, and year when reported. For drugs with three or more reports, the signal index was calculated using the Reporting Odds Ratio (ROR) method. In addition, the association between hypomagnesemia onset and other adverse events was investigated using association analysis. Results. The total number of reported hypomagnesemia cases was 201. Males accounted for 62.7%, and patients in their sixties formed a large peak. Three or more cases were reported for 23 causative drugs, among which anti-EGFR antibody, calcineurin inhibitor, platinum antitumor agent and proton pump inhibitor accounted for the majority. ROR analysis detected signals for 18 drugs, and an association was found between hypomagnesemia and other electrolyte abnormalities for those drugs. The median time until onset of hypomagnesemia was classified into three patterns: around 10 days, around 30 days, and longer. Analysis of the report year revealed an increasing tendency in recent years, although increases/decreases were evident depending on fiscal years. Conclusion. Our survey was able to reveal the factors associated with the occurrence of hypomagnesemia.

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Exploring the Mechanisms Underlying Drug-Induced Fractures Using the Japanese Adverse Drug Event Reporting Database

Pharmaceuticals ◽

10.3390/ph14121299 ◽

2021 ◽

Vol 14 (12) ◽

pp. 1299

Author(s):

Shinya Toriumi ◽

Akinobu Kobayashi ◽

Hitoshi Sueki ◽

Munehiro Yamamoto ◽

Yoshihiro Uesawa

Keyword(s):

Bone Resorption ◽

Adverse Drug Event ◽

Multiple Logistic Regression Analysis ◽

Principal Component ◽

Drug Event ◽

Drug Induced ◽

Dopaminergic Drugs ◽

Femur Fractures ◽

Increase Fracture Risk ◽

Induced Fractures

Fractures occur when bones become fragile and are subjected to external forces as occurring during falls. The use of drugs that increase bone fragility or fall risk increases the risk of fracture. This study investigates drug-induced fractures reported in the Japanese Adverse Drug Event Report (JADER) database in patients using 4892 drugs. Atypical femur fracture was the most frequently reported fracture, and 58 other fractures were also reported. Using Volcano plots and multiple logistic regression analysis, we identified the risk factors for drug-induced fractures as being female, of older age, higher body mass index, and using one of 90 drugs. The drug groups significantly associated with drug-induced fractures included bone resorption inhibitors, antiviral drugs, dopaminergic drugs, corticosteroids, and sleep sedatives. Principal component analysis was used to examine the relationship between the use of specific drugs and the site of drug-induced fracture. Bone resorption inhibitors and corticosteroids were associated with atypical femur fractures, jaw fractures, and ulna fractures through an osteoclast-mediated process. Other drugs were found to increase fracture risk via non-osteoclast-mediated mechanisms. These findings suggest that many drugs can result in drug-induced fractures through a variety of mechanisms.

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Analysis of Drug-Induced Gastrointestinal Obstruction and Perforation Using the Japanese Adverse Drug Event Report Database

Frontiers in Pharmacology ◽

10.3389/fphar.2021.692292 ◽

2021 ◽

Vol 12 ◽

Author(s):

Riko Satake ◽

Kiyoka Matsumoto ◽

Mizuki Tanaka ◽

Ririka Mukai ◽

Kazuyo Shimada ◽

...

Keyword(s):

Prescription Drugs ◽

Adverse Drug Event ◽

Barium Sulfate ◽

Gastrointestinal Perforation ◽

Drug Event ◽

Event Report ◽

Drug Induced ◽

X Ray ◽

Gastrointestinal Obstruction ◽

Time To Onset

Drug-induced gastrointestinal obstruction (DIGO) and gastrointestinal perforation (DIGP) may be the result of gastrointestinal hypomotility and severe constipation, which may lead to potentially fatal complications of bowel ischemia, sepsis and perforation. We evaluated the onset profile of DIGs (DIGO and DIGP) associated with prescription drugs by analyzing data in the Japanese Adverse Drug Event Report (JADER) database. We selected 161 DIG-related drugs and categorized them into 19 classes based on the Anatomical Therapeutic Chemical (ATC) Classification System. Finally, we focused on 58 drugs and conducted subsequent analyses for the time-to-onset and outcomes. We extracted 79 preferred terms (PTs) with the strings “ileus,” “stenosis,” “obstruction,” “obstructive,” “impaction,” “perforation,” “perforated,” “hypomotility,” and “intussusception” from the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) of SMQ20000104: gastrointestinal perforation, ulcer, hemorrhage, obstruction non-specific findings/procedures; SMQ20000105: gastrointestinal obstruction; and SMQ20000107: gastrointestinal perforation. Among the 667, 729 reports in the JADER database submitted between April 2004 and November 2020, we identified 11,351 occurrences of DIGs. The reporting odds ratios (RORs) (95% confidence interval) of “barium sulfate containing X-ray media,” “drugs for treatment of hyperkalemia and hyperphosphatemia,” and “oral bowel cleanser” were 142.0 (127.1–158.6), 25.8 (23.1–28.8), and 29.7 (24.8–35.6), respectively. The median number of days (interquartile range) until the onset of an adverse event caused by each drug category was as follows: barium sulfate containing X-ray contrast media [2.0 (1.0–3.0)], diazepines, oxazepines, thiazepines, and oxepines [8.0 (8.0–18.5)], drugs for treatment of hyperkalemia and hyperphosphatemia [29.0 (8.0–55.0)], non-selective monoamine reuptake inhibitors [19.0 (7.0–47.5)], and oral bowel cleanser [0.0 (0.0–0.0)]. Depending on the drug, the time to onset of side effects ranged from days to several months. Our results highlighted the need to perform detailed monitoring of each drug for possible association with DIGs, which might otherwise have fatal consequences.

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Risk Assessment for Anti-Infectives-Related Acute Kidney Injury Using the Japanese Adverse Drug Event Report Database

10.21203/rs.3.rs-41018/v1 ◽

2020 ◽

Author(s):

Satoshi Nakao ◽

Shiori Hasegawa ◽

Ryogo Umetsu ◽

Kazuyo Shimada ◽

Ririka Mukai ◽

...

Keyword(s):

Acute Kidney Injury ◽

Adverse Drug Event ◽

Association Rule ◽

Association Rule Mining ◽

Kidney Injury ◽

Drug Event ◽

Event Report ◽

Rule Mining ◽

Drug Induced ◽

Medical Dictionary

Abstract Background: Acute kidney injury (AKI) is associated with significant increases in short- and long-term morbidity and mortality. Drug-induced AKI is a major concern in the present healthcare system. Our spontaneous reporting system (SRS) analysis assessed links between AKIs, along with patients’ age, as healthcare-associated risks and administered anti-infectives. We also generated anti-infectives-related AKI-onset profiles.Method: We calculated adjusted reporting odds ratios (RORs) for reports of anti-infectives-related AKIs (per Medical Dictionary for Regulatory Activities) in the Japanese Adverse Drug Event Report database and evaluated associations between anti-infectives and age by association rule mining. We evaluated time-to-onset data and hazard types using the Weibull parameter.Results: Among 534,688 reports (submission period: April 2004–June 2018), there were 21,727 AKI events. Anti-infective treatments including glycopeptide antibacterials, fluoroquinolones, third-generation cephalosporins, triazole derivatives, and carbapenems were associated with 596, 494, 341, 315, and 313 AKI incidences, respectively. Adjusted RORs of anti-infectives-related AKIs increased among older patients and were higher in anti-infective combination therapies [anti-infectives, ≥ 2; ROR, 2.75 (2.56–2.95)] than in monotherapies [ROR, 1.52 (1.45–1.61)]. In association rule mining, the number of anti-infectives and age were associated with anti-infectives-related AKI lift values (as consequent). Moreover, 48.1% of AKIs occurred within 5 days (median, 5.0 days) of anti-infective therapy initiation.Conclusion: Thus, adjusted RORs derived from our new SRS analysis indicate potential AKI risks linked to age and number of administered anti-infectives.

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