Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary informati...Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.展开更多
Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DIL...Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI,especially in idiosyncratic liver injury.This study examined liver injury reports submitted to the Food and Drug Administration(FDA) Adverse Event Reporting System(FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity.The frequency of hepatotoxicity was determined at a group level and individual drug level.A reporting odds ratio(ROR) was calculated as the measure of effect.Between the two DILI groups,reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43(95% CI 1.42-1.45;P <0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity.Antineoplastic,antiviral,analgesic,antibiotic,and antimycobacterial drugs were the top five drug classes with the highest ROR values.Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms,the top four drugs(ROR values> 18:benzbromarone,troglitazone,isoniazid,rifampin) were associated with mitochondrial mechanisms of toxicity.The major demographic influence for DILI risk was also examined.There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1±18.33(SD)] compared to non-mitochondrial mechanisms [48±19.53(SD)](P <0.0001),suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity.Univariate logistic regression analysis showed that reports of liver injury were 2.2(odds ratio:2.2,95% CI 2.12-2.26) times more likely to be associated with older patient age,as compared with reports involving patients less than 65 years of age.Compared to males,female patients were 37% less likely(odds ratio:0.63,95% CI 0.61-0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms.Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity,it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives,more clinically relevant animal models,and better clinical biomarkers may provide a better translation of druginduced mitochondrial toxicity risk assessment from animals to humans.Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI,and this should be further investigated in real-world studies with robust designs.展开更多
回顾性分析了美国食品药品监督管理局制造商和用户设施设备体验(Manufacturer and User Facility Device Experience,MAUDE)数据库2021年1月至2024年6月的弹簧圈不良事件,结合山东省内医院调研和专家论证情况指出了弹簧圈在临床使用过...回顾性分析了美国食品药品监督管理局制造商和用户设施设备体验(Manufacturer and User Facility Device Experience,MAUDE)数据库2021年1月至2024年6月的弹簧圈不良事件,结合山东省内医院调研和专家论证情况指出了弹簧圈在临床使用过程中存在的风险点并进行了原因分析,提出了落实注册人的主体责任、提高使用单位的专业技能、强化监管部门的监管力度等改进措施,为弹簧圈的安全使用提供了参考。展开更多
Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present s...Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present study was to evaluate the onset time profiles for syncope associated with the use of α1Bs. Methods: We analyzed the data obtained from?the Japanese Adverse Drug Event Report (JADER) database for a period from April 2004 until November 2016 and calculated reporting odds ratios (RORs) for eight α1Bs available on the Japanese market, using disproportionality analysis. Moreover, time information recorded in the JADER database was analyzed to evaluate the onset times of adverse events. Results: In total, 186,724 reports for males older than 20 years were analyzed. Significant RORs for syncope, with 95% confidence intervals, were obtained for naftopidil (2.53, 1.81 - 3.53), silodosin (4.24, 2.37 - 5.20), and tamsulosin (2.22, 1.75 - 2.81). The median onset times of syncope for naftopidil, silodosin, and tamsulosin were 37, 26, and 108 days, respectively. The shape parameters obtained by fitting the data for the three α1Bs to the Weibull distribution were all less than 1.0, indicating that all these drugs could be classified as the early failure type. The cumulative incidence rates showed that the onset times of syncope tended to be similar among the three α1Bs. Conclusions: Patients treated with selective α1Bs should be closely monitored for 100 days, especially in the first 20 to 40 days after initiation of silodosin or naftopidil. This information may be useful for patients and healthcare professionals in preventing syncope due to the use of selective α1Bs.展开更多
基金The 2022 Educational Teaching Reform and Research Project of Guangxi University of Traditional Chinese Medicine(2022C032).
文摘Background:Lenvatinib is primarily utilized for the treatment of inoperable or advanced hepatocellular carcinoma,radioiodine-refractory differentiated thyroid cancer,and advanced renal cell carcinoma.Primary information about adverse reactions is principally derived from clinical trials;however,there is a notable dearth of substantial real-world studies.Methods:In this research,an examination of the U.S.Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database was performed to evaluate the potential side effects of lenvatinib.The FAERS database revealed a total of 20,290 reported adverse events associated with lenvatinib.Different algorithms for repeated measure analysis were employed to ascertain the significance of these adverse reactions.Results:The study identified 170 instances of adverse events(AEs)induced by lenvatinib,incorporating several significant adverse reactions that the product label does not mention.The investigation also evaluated the onset periods of the adverse reactions,pinpointing a median time of 43 days.The majority of adverse reactions manifested within the initial month of lenvatinib use.Sex-specific analysis revealed disparities in high risk adverse reactions between females(vascular and lymphatic diseases,and neuronal organ diseases)and males(death and infectious diseases).Our data mining has unveiled adverse reactions beyond those mentioned within the instructions,such as osteonecrosis of the jaw,cholecystitis,cholangitis,dehydration,tumor lysis syndrome,type 1 diabetes,hyperammonemia,liver abscess,interstitial lung disease,pneumothorax,sudden death,and aortic dissection.Conclusion:The insights derived from these findings contribute significant nuances for optimizing lenvatinib use,enhancing its efficacy,and substantially mitigating potential side effects.These data elements will substantially enhance the implementation of the drug in a clinical environment.
文摘Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI,especially in idiosyncratic liver injury.This study examined liver injury reports submitted to the Food and Drug Administration(FDA) Adverse Event Reporting System(FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity.The frequency of hepatotoxicity was determined at a group level and individual drug level.A reporting odds ratio(ROR) was calculated as the measure of effect.Between the two DILI groups,reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43(95% CI 1.42-1.45;P <0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity.Antineoplastic,antiviral,analgesic,antibiotic,and antimycobacterial drugs were the top five drug classes with the highest ROR values.Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms,the top four drugs(ROR values> 18:benzbromarone,troglitazone,isoniazid,rifampin) were associated with mitochondrial mechanisms of toxicity.The major demographic influence for DILI risk was also examined.There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1±18.33(SD)] compared to non-mitochondrial mechanisms [48±19.53(SD)](P <0.0001),suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity.Univariate logistic regression analysis showed that reports of liver injury were 2.2(odds ratio:2.2,95% CI 2.12-2.26) times more likely to be associated with older patient age,as compared with reports involving patients less than 65 years of age.Compared to males,female patients were 37% less likely(odds ratio:0.63,95% CI 0.61-0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms.Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity,it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives,more clinically relevant animal models,and better clinical biomarkers may provide a better translation of druginduced mitochondrial toxicity risk assessment from animals to humans.Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI,and this should be further investigated in real-world studies with robust designs.
文摘回顾性分析了美国食品药品监督管理局制造商和用户设施设备体验(Manufacturer and User Facility Device Experience,MAUDE)数据库2021年1月至2024年6月的弹簧圈不良事件,结合山东省内医院调研和专家论证情况指出了弹簧圈在临床使用过程中存在的风险点并进行了原因分析,提出了落实注册人的主体责任、提高使用单位的专业技能、强化监管部门的监管力度等改进措施,为弹簧圈的安全使用提供了参考。
文摘Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present study was to evaluate the onset time profiles for syncope associated with the use of α1Bs. Methods: We analyzed the data obtained from?the Japanese Adverse Drug Event Report (JADER) database for a period from April 2004 until November 2016 and calculated reporting odds ratios (RORs) for eight α1Bs available on the Japanese market, using disproportionality analysis. Moreover, time information recorded in the JADER database was analyzed to evaluate the onset times of adverse events. Results: In total, 186,724 reports for males older than 20 years were analyzed. Significant RORs for syncope, with 95% confidence intervals, were obtained for naftopidil (2.53, 1.81 - 3.53), silodosin (4.24, 2.37 - 5.20), and tamsulosin (2.22, 1.75 - 2.81). The median onset times of syncope for naftopidil, silodosin, and tamsulosin were 37, 26, and 108 days, respectively. The shape parameters obtained by fitting the data for the three α1Bs to the Weibull distribution were all less than 1.0, indicating that all these drugs could be classified as the early failure type. The cumulative incidence rates showed that the onset times of syncope tended to be similar among the three α1Bs. Conclusions: Patients treated with selective α1Bs should be closely monitored for 100 days, especially in the first 20 to 40 days after initiation of silodosin or naftopidil. This information may be useful for patients and healthcare professionals in preventing syncope due to the use of selective α1Bs.
