Signal mining of valproic acid-induced adverse drug events based on FAERS / 中国药房

OBJECTIVE To provide reference for clinically safe and rational drug use through mining and analyzing adverse drug event （AE） signals induced by valproic acid （VPA）. METHODS Reporting Odds Ratio （ROR） and Bayesian Confidence Propagation Neural Network （BCPNN） methods of Measures of Disproportionality were performed to mine and analyze the data of VPA-related AE reports in the US FDA Adverse Event Reporting System （FAERS） database from the first quarter of 2013 to the fourth quarter of 2022. RESULTS A total of 1 253 （ROR） and 1 109 （BCPNN） valid signals of preferred terms （PT） were obtained after data processing by the two analysis methods， involving 27 system organs （SOC）， mainly focusing on nervous system disorders， psychiatric disorders， general disorders and administration site conditions. Signals that did not appear in the instruction were associated with 2 SOCs： ear and labyrinth disorders， infections and infestations. CONCLUSIONS As a first-line broad-spectrum anti-epileptic drug， attention should also be paid to eye toxicity and infection risk in the clinical application in addition to paying attention to common adverse events in the instruction.

Mining and analysis of adverse drug events signals of nilotinib based on FDA adverse event database / 中国药房

OBJECTIVE To provide a reference for safe drug use in clinic. METHODS ADE reports related to nilotinib from the first quarter of 2007 to the fourth quarter of 2022 were collected from the US FDA adverse event reporting system database. The reporting odds ratio （ROR） and proportional reporting ratio （PRR） of disproportionality measures were used to mine potential ADE signals，which were compared with drug instruction and related case report， and were screened and analyzed according to the designated medical events （DME） list formulated by the European Medicines Agency. RESULTS Totally 23 332 cases of ADE with nilotinib as the primary suspected drug were reported. A total of 359 positive signals were obtained，involving 24 system organ classes （SOC），mainly concentrated in various examinations，heart organ diseases，vascular and lymphatic diseases，all kinds of nervous system diseases，etc. Among them，ADEs such as vertebral artery stenosis，coronary artery stenosis，arterial disease，liver infection and the second primary malignant tumor were not mentioned in the instructions. Seven DMEs were detected，of which bone marrow failure，pulmonary hypertension and deafness were not mentioned in the drug instruction. CONCLUSIONS The common ADE signals of nilotinib excavated in this study are consistent with the instructions. In clinical use，special attention should be paid to DME not mentioned in the instructions such as bone marrow failure，pulmonary hypertension and deafness； cardiac function， blood glucose and blood lipid indexes should be monitored closely.

Nivolumab-associated pulmonary toxicities： a retrospective study based on FARES database from 2016 to 2019 / 上海预防医学

Objective:Nivolumab is one of the most common programmed death 1 （PD-1） inhibitors used as an immune checkpoint inhibitor （ICI）. It brings significant therapeutic effects but often accompanied by serious drug toxicity. The pulmonary toxicities of nivolumab are not clear. This study aims to systematically explore the nivolumab-associated pulmonary toxicities and provide reference for clinical treatment. Methods:Data were extracted from US Food and Drug Administration （FDA） Adverse Event Reporting System （FAERS） database from January 1， 2016 to September 30， 2019. Two types of disproportionality analysis， information component （IC） and reporting odds ratio （ROR）， were applied in nivolumab-associated pulmonary adverse events （AEs） signal detection. Results:A total of 28 489 309 records were extracted from FAERS database and 8 181 records were associated with nivolumab. Analysis was conducted in 179 AEs and 86 signals were detected. Notably， potent signals were detected in radiation pneumonitis （IC025： 3.99， ROR025： 17.25）， pneumonitis （IC025： 3.34， ROR025： 10.64） and bronchial fistula （IC025： 2.94， ROR025： 8.78）. Nivolumab-associated pulmonary toxicities were more frequently reported in dyspnoea （IC025： 0.50， ROR025： 1.44）， pneumonia （IC025： 0.08， ROR025： 1.07） and pneumonitis （IC025： 3.34， ROR025： 10.64）. Results of IC and ROR methods were similar to each other. Most pulmonary toxicities were observed in patients with non-small cell lung cancer （N=3 711， 32.13%）， malignant melanoma （N=1 658， 14.36%） and renal cell carcinoma （N=731， 6.33%）. Conclusion:Significant pulmonary toxicities were detected in patients treated with nivolumab. Thus， it is highly important for clinicians to be vigilant about nivolumab-associated pulmonary AEs and be prepared to take immediate action for patient safety.

Study on ADR Signal Detection of Dasatinib and Imatinib / 中国药房

OBJECTIVE:To mine the ADR signals of dasatinib and imatinib,and to provide reference for safe use of two drugs in clinic. METHODS:ROR and PRR method of disproportionality measures were used to mine the data in the reports about dasatinib and imatinib of 17 quarters from FDA ADE Reporting System during the fourth quarter of 2012-the fourth quarter of 2016. ADR description terms in reports were standardized with international medical terms dictionary. ADR with signal detected by both methods were screened again. RESULTS & CONCLUSIONS:Totally 505 ADR signals for dasatinib and 929 ADR signals for imatinib had been found by ROR and PRR. After re-screening,there were 351 ADR signals for dasatinib and 649 ADR signals for imatinib,including 153 ADR signals for both dasatinib and imatinib. ADR signals for both dasatinib and imatinib obtained in this study were in agreement with known safety information. ADR mainly occurred in gastrointestinal tract,blood and lymphatics,kidney and urinary system,cardiovascular and musculoskeletal tissue,etc. However,incomplete information in the instructions was also found,such as possible urinary system-related ADR signals caused by dasatinib were detected in this study is not mentioned in drug instruction;imatinib could cause ADR signals of left atrium and right atrium dilation,which were not included in their instructions. Common ADRs,such as headaches,metioned in drug instructions of imatinib,did not appear in the top 50 signal intensities in this study. In addition,the ADR of the two drugs also varied,such as 7 ADR signals as periorbital edema and ocular edoma of forimatinib were much stronger than dasatinib;5 ADR signals of dasatinib,such as pericardial effusion and pleural effusion were much stronger than imatinib,indicating clinical drug selection should be based on individual situation of patients.