Risk of immune system and skin and subcutaneous tissue related adverse events associated with oxaliplatin combined with immune checkpoint inhibitors: a pharmacovigilance study.

Background: Few studies have analysed oxaliplatin-induced adverse events (ADEs) in the immune system and skin and subcutaneous tissues through pharmacovigilance. We used this approach to analyse the risk of such ADEs when oxaliplatin combined with immune checkpoint inhibitors (ICIs). Methods: We evaluated the association between oxaliplatin and ADEs in the immune system and skin and subcutaneous tissues using the reporting odd ratio (ROR) for mining the ADE report signals in the FDA Adverse Event Reporting System database. Risk factors were analyzed using a binary logistic regression analysis using the sex and age of the patients. Results: There were 40,474 reports of oxaliplatin as primary suspect drug or second suspect drug. The signal intensities of ADEs such as type II hypersensitivity, type I hypersensitivity, type III immune complex-mediated reaction, anaphylactoid shock and cytokine release syndrome were high in PTs classified by SOC as immune system disorders; in the PTs classified as skin and subcutaneous tissue disorders by SOC, the signal intensities of ADEs such as skin toxicity, skin reaction, rash maculo-papular and skin fissures were higher. In the risk assessment between the two groups, rash showed an increased risk in the oxaliplatin-ICI group, with an OR of 1.96. Nivolumab in combination with oxaliplatin had an OR of 2.196 and an adjusted OR of 2.231. Combined with pembrolizumab, OR was 2.762 and the adjusted OR was 2.678. Conclusion: Type II hypersensitivity shows a stronger pharmacovigilance signal. Oxaliplatin in combination with nivolumab or pembrolizumab has been shown to increase the risk of rash.

Safety evaluation of ceftazidime/avibactam based on FAERS database.

OBJECTIVE: To explore adverse event (AE) signals of Ceftazidime/avibactam (CZA) based on the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports primarily associated with CZA were retrieved from the FAERS database from the second quarter of 2015 to the second quarter of 2023. Signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS) methods. RESULTS: A total of 750 AEs reports with CZA as the preferred suspected drug were obtained, identifying 66 preferred terms (PTs) involving 24 system organ classes (SOCs). Besides, the AEs already mentioned in the drug label, this study also revealed some new, clinically valuable potential AEsignals, such as Cholestasis (n = 14, ROR 29.39, PRR 29.15, IC 3.34, EBGM 29.11), Drug-induced liver injury (n = 8, ROR 9.05, PRR 9.01, IC 2.25, EBGM 9.01), Hepatocellular injury (n = 7, ROR 13.90, PRR 13.84, IC 2.41, EBGM 13.63), Haemolytic anaemia (n = 5, ROR 24.29, PRR 24.22, IC 2.42, EBGM 40.53), etc. Additionally, AE signals with higher intensity were identified, such as Hypernatraemia (n = 5, ROR 40.73, PRR 40.61, IC 2.31, EBGM 24.19), Toxic epidermal necrolysis (n = 4, ROR 11.58, PRR 11.55, IC 1.89, EBGM 11.54). Therefore, special vigilance for these potential AEs is warranted when using CZA clinically. CONCLUSION: This study highlights the potential AEs and risks associated with the clinical use of CZA, particularly the risks related to Cholestasis, Drug-induced liver injury, Haemolytic anaemia, Hypernatraemia, and Toxic epidermal necrolysis.

Exploring adverse events of Vilazodone: evidence from the FAERS database.

OBJECTIVE: This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. METHODS: This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. RESULTS: The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). CONCLUSION: Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

Detection and analysis of signals of adverse events of memantine based on the US food and drug administration adverse event reporting system.

BACKGROUND: Despite its widespread use, the adverse effects (AEs) of memantine have not been well documented, and there is a need to find new ways to analyze the AEs of memantine. RESEARCH DESIGN AND METHODS: AEs in which the primary suspected drug was memantine were retrieved from the FAERS database. The proportional report ratio (PRR), reporting odds ratio (ROR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM) were used to detect potential positive signals between memantine and AEs. SAS, MySQL, EXCEL, and R language software were used for data processing and statistical analysis. RESULTS: This study gathered a total of 5808 reports of AEs associated with memantine. Of these reports, a greater proportion of female patients (51.17%) than male patients (36.33%) had AEs. The AEs reported by FAERS were mainly in psychiatric category (n = 2157, IC025 = 2.69), various neurologic disorders (n = 1608, IC025 = 2.04), systemic disorders and various site reactions (n = 842, IC025 = 1.29). Unexpected ocular adverse events have been reported, ophthalmic vein thrombosis (n = 4, IC025 = 3.47) and scleral discolouration (n = 7, IC025 = 3.1), which may worsen glaucoma. CONCLUSIONS: This study observed conceivable new AEs signals and may supply important assist for scientific monitoring and threat identification of memantine.

PD-1/PD-L1 inhibitors-associated cardiac adverse events: a retrospective and real-world study based on the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors have reformed the treatment landscape for various malignancies and improved prognosis of patients. However, they also lead to events that although rare may prove to be fatal. RESEARCH DESIGN AND METHODS: Data from July 2014 to June 2022 based on FDA Adverse Event Reporting System (FAERS) were analyzed. The signal index reporting odds ratio (ROR) was used to evaluate the correlation between cardiac AEs and given medications. The indications and the median time to onset (TTO) of different PD-1/PD-L1 inhibitors were compared. RESULTS: Cardiac AEs are rare but may be fatal with particular profiles in primary tumor, onset time, and especially gender. We identified 11,538 reports that were related to cardiotoxicity of PD-1/PD-L1 inhibitors, in which 178 different preferred terms (PTs) were distinguished, and nivolumab reported the most PTs with signal. All targeted medications showed signals in myocardial disorders and pericardial disorders, which tend to occur in the first 1-2 months. Non-small cell neoplasm was the top and common indication during anti-PD-1 or anti-PD-L1 therapy with cardiotoxicity. CONCLUSIONS: This study could help early diagnosis and surveillance of ICIs-related cardiotoxicity.

Signal mining study of severe cutaneous adverse events of valaciclovir or acyclovir based on the FAERS database.

OBJECTIVE: This study aimed to explore a comprehensive empirical investigation and assess SCARs related to valaciclovir or acyclovir based on FAERS database from FDA, thus providing a theoretical foundation for the rational application of drugs in clinic. METHODS: SCARs reports relevant to valaciclovir or acyclovir were searched in FAERS database from the 2004 Q1 to 2023 Q2. These data were further mined by a proportional analysis and Bayesian approach to detect signals of SCARs caused by two drugs. Meanwhile, the clinical characteristics, onset time, correlation, and stratification analysis of the two drugs in SCARs were analyzed. RESULTS: Both drugs exhibited positive signals for drug reaction with DRESS, AGEP, TEN, SJS-TEN overlap and SJS. The median onset time of SCARs caused by valaciclovir or acyclovir was 30 days vs 10 day for DRESS, 11 days vs 9 days for AGEP, 17 days vs 12 days (TEN) and 12 days vs 8 days (SJS). Excluding the effect of combinational drugs, there was an association between the two antiviral drugs and SCARs. CONCLUSION: By analyzing the FAERS database, the risk trends of SCARs caused by valaciclovir or acyclovir have been identified, providing valuable insights to recognize various types of SCARs in clinics.

Data mining and analysis of oxaliplatin-related adverse events of nervous system / 中国药房

OBJECTIVE To provide reference for clinically safe drug use by mining oxaliplatin-related adverse drug events （ADE） of the nervous system. METHODS Oxaliplatin-related neurologic ADE data reported by the FDA adverse event reporting system （FAERS） between January 1st， 2004 and December 31st， 2022 were collected. The reporting odds ratio and proportional reporting ratio were used for data mining. The data were classified statistically by using systematic organ classification， high-level group term （HLGT） and preferred term （PT） in the MedDRA （version 26.0）. RESULTS A total of 7 266 cases of oxaliplatin- related ADE， which were classified as various neurological， were retrieved， and 100 PT were identified. Of these， fifty-seven PT were unspecified adverse reaction signals in the manual. Among these reports， males （46.85%） were more than females （42.98%）， the age of patients was 45-＜75 years （65.22%）， the number of reports was highest in Italy （16.32%）， and the severe type was hospitalization or prolonged hospitalization （38.16%）. The top 5 PT reports in the list of case number were peripheral neuropathy， paresthesia， neurotoxicity， loss of consciousness and dysarthria. The top 5 PT reports in the list of signal intensities were cold- induced paresthesia， neuromuscular rigidity， acute polyneuropathy， neuronal neuropathy， axonal and demyelinating polyneuropathy. A total of 13 HLGT were involved， with neurological diseases （not classified separately） having the highest number of signals （29）. CONCLUSIONS When using oxaliplatin in clinical practice， it is not only necessary to monitor the high incidence of acute and chronic peripheral neuropathy， but also to pay attention to the patient’s consciousness state and neurological symptoms. We should pay attention to the rare types of adverse reactions， such as guillain-barre syndrome， Lhermitte sign， posterior reversible encephalopathy syndrome， and hyperammoniacal encephalopathy， so as to ensure the safety of medication.

Signal mining and analysis of adverse drug event signals of darolutamide / 中国药房

OBJECTIVE To explore and analyze the adverse drug event （ADE） signals of darolutamide and provide a reference for its clinical safe use. METHODS ADEs related to darotamide were collected based on the US FDA adverse event reporting system （FAERS） database from the third quarter of 2019 to the third quarter of 2022. Data mining and analysis were conducted by the report odds ratio （ROR） and proportional reporting ratio （PRR） methods. RESULTS A total of 565 ADE reports related to darolutamide were extracted， 356 ADE reports about darolutamide as the primary suspected drug were included， 38 ADE signals with darolutamide as the primary suspected drug were excavated， involving 15 system organ class （SOC）， mainly concentrated in patients over 65 years old. The SOC of darotamide ADE signal mainly focused on various examinations， systemic diseases and various reactions at the administration site， benign/malignant tumors or those with unknown nature （including cystic and polypoid）， kidney and urinary system diseases. A total of 13 ADE signals not mentioned in the instructions included increased prostate-specific antigen， dysphagia， cognitive impairment， erectile dysfunction， rhabdomyolysis， gynecomastia and decreased platelet count， etc. CONCLUSIONS When using darolutamide， in addition to ADE in the drug instruction， we should pay close attention to potential ADE， such as increased prostate-specific antigen， rhabdomyolysis， gynecomastia and decreased platelet count， so as to avoid drug withdrawal or organ damage caused by ADE.

Signal mining and analysis of selinexor adverse events / 中国药房

OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

Signal mining and analysis of adverse events of oseltamivir，zanamivir and baloxavir marboxil / 中国药房

OBJECTIVE To provide reference for safe drug use in clinic by mining the adverse drug events （ADE） of 3 kinds of anti-influenza A virus drugs （oseltamivir， zanamivir， baloxavir marboxil）. METHODS The ADE data of oseltamivir， zanamivir and baloxavir marboxil were collected from the FDA adverse event reporting system （FAERS） between the first quarter in 2004 and the third quarter in 2022， and mined by using reporting odds ratio （ROR） method. The designated medical events （DME） were estimated. The system organ class （SOC） in the Medical Dictionary for Regulatory Activities （MedDRA， version 25.0） was used for the classification and statistics of drug ADE terminology. RESULTS A total of 12 636， 1 749 and 1 283 ADE reports were retrieved for oseltamivir， zanamivir and baloxavir marboxil， involving 26， 16 and 17 SOCs， respectively. Oseltamivir was strongly associated with sleep terror， abnormal behavior， hallucination and delirium. Zanamivir was implicated in abnormal behavior， delirium， incoherence， and altered state of consciousness with prominent signal intensity. Baloxavir marboxil was strongly associated with ischemic colitis， hemorrhagic cystitis， erythema multiforme and melaena. Erythema multiform was detected in the DME of three drugs with strong signals. CONCLUSIONS When clinically administering the three drugs， it is crucial to pay close attention to both common adverse reactions and those ADEs that are not explicitly mentioned in the drug instructions. For oseltamivir， clinicians should exercise caution due to the potential risk of acute kidney injury and fulminant hepatitis， necessitating regular monitoring of the patient’s liver and kidney function. When prescribing zanamivir， caution should be exercised due to ADEs related to the respiratory system， including acute respiratory distress syndrome and respiratory failure， necessitating close monitoring of the patient’s respiratory status. Similarly， for baloxavir marboxil， clinicians should be vigilant for potential ADEs such as erythema multiforme and rhabdomyolysis.

Signal mining and analysis for central nervous system adverse events due to taking oxycodone based on FAERS database. / 基于FAERSæ•°æ®åº“çš„ç¾Ÿè€ƒé ®ä¸­æž¢ç¥žç»ç³»ç»Ÿä¸è‰¯äº‹ä»¶ä¿¡å·æŒ–æŽ˜åŠåˆ†æž.

OBJECTIVES: Central nervous system adverse events (AEs) occur when oxycodone is used in combination with benzodiazepines, antidepressants and anticonvulsants. There have been no reports of central nervous system AEs with oxycodone alone or in combination with oxycodone. Based on USA Food and Drug Administration Adverse Event Reporting System (FAERS) data, this study aims to explore the risk signals of central nervous system AEs with oxycodone alone or in combination with benzodiazepines, antidepressants and anticonvulsants, and to provide a reference for the safe and rational use of this drug. METHODS: Extracted AEs data from the FAERS for oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants from Q1 2004 to Q2 2021. The risk signal mining analysis of AEs was performed using the proportional imbalance method and Bayesian method. Number of reports ≥3 and lower 95% CI limit of reporting odds ratio (ROR)>1; number of reports ≥3, proportional reporting ratio (PRR)≥2 and χ2≥4; lower information components (IC) lower 95% CI limit (IC025)>0; empirical Bayes geometric mean (EBGM) lower 95% CI limit (EBGM05)>2, and N>0 were defined as positive signals. RESULTS: A total of 5 793 reports of central nervous system AEs with oxycodone alone were tapped, and 366, 622, and 740 reports of combined benzodiazepines, antidepressants, and anticonvulsants, respectively. Consumers and physicians were the main reporting population. The age distribution of oxycodone alone was mainly from 61 to 80 years old. The age distribution of oxycodone in combination with related drugs was mainly from 46 to 60 years old. The risk of AEs was greater in women than in men, and the United States was the predominant reporting country. Oxycodone alone was strongly associated with myoclonus [ROR=2.92, 95% CI 2.28 to 3.76); PRR=2.92, χ2(77.49); IC=1.52, IC025(0.65); EBGM=2.89, EBGM05(2.33)], delirium [ROR=4.69, 95% CI 4.24 to 5.21; PRR=4.66, χ2(1 052.64); IC=2.17, IC025(1.81); EBGM=4.50, EBGM05 (4.13)], mental disorder [ROR=2.95, 95% CI 2.53 to 3.44; PRR=2.94, χ2(206.93); IC=1.56, IC025(0.96); EBGM=2.95, EBGM05(2.58)], and acute central respiratory depression [ROR=2.87, 95% CI 2.68 to 3.08); PRR=2.82, χ2(971.62); IC=1.52, IC025(1.33), EBGM=2.87, EBGM05 (2.76)]. Combination of benzodiazepines was most strongly associated with mental disorder [ROR=10.08, 95% CI 9.38 to 10.78; PRR=9.90, χ2(64.06); IC=3.33, IC025 (1.65); EBGM=10.08, EBGM05(5.61)], and tremor [ROR=3.09, 95% CI 2.76 to 3.42); PRR=3.08, χ2(48.93); IC=1.63, IC025 (1.17); EBGM=3.09, EBGM05(2.34)]. Combination of antidepressants was most strongly associated with delirium [ROR=13.23, 95% CI 12.23 to 14.23; PRR=12.87, χ2(43.86); IC=3.69, IC025(1.36); EBGM=12.23, EBGM05 (5.32)] and somnolence [ROR=6.74, 95% CI 6.15 to 7.33); PRR=6.73, χ2(53.42); IC=2.75, IC025(1.52); EBGM=6.73, EBGM05(4.10)]. Combination of anticonvulsants was most strongly associated with myoclonus [ROR=17.89, 95% CI 17.46 to 18.32; PRR=17.72, χ2(971.39); IC=4.16, IC025(2.70); EBGM=17.89, EBGM05(12.46)] and delirium [ROR=4.86, 95% CI 4.45 to 5.27); PRR=4.82, χ2(69.49); IC=2.28, IC025 (1.51); EBGM=4.86, EBGM05(3.44)]. CONCLUSIONS: Based on pharmacovigilance studies of the FAERS database, clinical medication monitoring of oxycodone alone and in combination with benzodiazepines, antidepressants, and anticonvulsants should be strengthened to be alert to the occurrence of central nervous system-related AEs.

Risk signal mining of ixazomib based on the database of FAERS / 中国药房

OBJECTIVE To explore the risk signal of ixazomib and provide a reference for clinically rational drug use. METHODS The Open Vigil 2.1 online tool was used to extract the data of adverse drug events （ADE） reported by the database of FDA adverse event reporting system （FAERS） from the launch of ixazomib in America （November 20th， 2015） to the latest update of the Open Vigil website （March 31st， 2023）. The data were mined by using the proportional reporting ratio （PRR） and Bayesian confidence propagation neural network （BCPNN） of the proportional imbalance method. The signals were coded by system organ class （SOC） and preferred term （PT） according to MedDRA v25.1. RESULTS A total of 13 841 ADE reports with ixazomib as the “primary subject” were extracted， involving slightly more male patients （49.53%）， and most of them were 65 years old and above （72.48%）； the reports came from 57 countries/regions， mainly America （52.90%）. A total of 186 positive signals were excavated， with 51 high-intensity， 99 medium-intensity， and 36 low-intensity signals， involving 19 SOCs. The top 50 PT in frequency and signal intensity of PRR included neuropathy peripheral （414 cases， high-intensity signal）， platelet count decreased （379 cases， high-intensity signal）， thrombocytopenia （360 cases， high-intensity signal）， cytopenia （75 cases， high-intensity signal） and neurological symptoms （41 cases， high-intensity signal）. SOC involved included nervous system disorders， investigations， and blood and lymphatic system disorders. ADE occurred most frequently in gastrointestinal diseases （2 588 cases）， including diarrhea （1 077 cases， high-intensity signal）， nausea （737 cases， medium-intensity signal）， vomiting （459 cases， medium-intensity signal）， constipation （275 cases， medium-intensity signal）， and so on. The positive signals of infections and infestations contained the largest number of PTs， and most of them were not recorded in the drug instruction， including 12 high-intensity signals （1 030 cases） and 30 medium-intensity signals （627 cases）， which were mainly distributed in lung infection， upper respiratory infection， gastrointestinal infection， sepsis， herpes zoster and so on. The signals of cardiac amyloidosis （7 cases， high-intensity signal） and acute coronary syndrome （14 cases， high-intensity signal） of cardiac disorders and renal dysfunction （91 cases， medium-intensity signal） of renal and urinary disorders were all strong and had not been recorded in the drug instruction. CONCLUSIONS In addition to routine attention to the common ADE of ixazomib in gastrointestinal diseases，nervous system disorders and blood and lymphatic system disorders， clinical attention should also be paid to various infections that may occur during the treatment of patients， and the occurrence of cardiovascular toxicity and renal dysfunction should be monitored.

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.

Mining and analysis of lorlatinib-induced adverse drug event signals / 中国药房

OBJECTIVE To provide references for the safe use of lorlatinib in clinical practice. METHODS The reporting odds ratio （ROR） method， Medicines and Healthcare Products Regulatory Agency comprehensive standard method （referred to as “MHRA method”） and the Bayesian confidence propagation neural network （BCPNN） method were used to detect adverse drug events （ADEs） signals of lorlatinib in the FDA Adverse Event Reporting System from the first quarter of 2019 to the fourth quarter of 2022. RESULTS & CONCLUSIONS Totally 114 overlapping ADEs signals of lorlatinib were detected by the three methods， among which there were 73 new suspicious ADEs signals which were not covered in the instruction of lorlatinib. When using loratinib in clinical practice， special attention should be paid to ADEs with a high number of cases and signals， such as various neurological diseases， psychiatric diseases， respiratory system， thoracic and mediastinal diseases； clinical manifestations included cerebral edema， cerebral infarction， pulmonary hypertension， mutism， decreased sexual desire， pleural effusion. The signals of mobile thrombophlebitis， radiation necrosis， mutism， vesicoureteral reflux not mentioned in the instructions were all strong in BCPNN detection with high specificity， to which we should pay attention in clinical application.

Mining and analysis of ADE signals of romiplostim and eltrombopag based on FAERS database / 中国药房

OBJECTIVE To provide a reference for the safe use of thrombopoietin receptor agonists romiplostim and eltrombopag in clinic. METHODS FDA adverse event reporting system （FAERS） in the United States was adopted to collect adverse drug event （ADE） reports of romiplostim and eltrombopag from their launch in the United States to September 30， 2022； the ADE signals of the two drugs were analyzed using the reporting odds ratio （ROR） method and the comprehensive standard method of the UK Medicines and Healthcare Products Regulatory Agency. RESULTS A total of 14 021 and 4 431 ADE reports were collected about romiplostim and eltrombopag， respectively， with a gender composition of more females than males. After signal screening， 563 ADE signals were obtained about romiplostim， involving 25 system organ classes （SOC）； eltrombopag had 433 ADE signals， involving 26 SOC. The most frequently reported ADE for both drugs was platelet count decreased （2 060， 1 585 cases）， which was mentioned in their drug instructions. In terms of signal intensity， romiplostim exhibited the highest signal for abnormal thrombopoietin levels （ROR of 2 268.85）， while eltrombopag had the highest signal for positive dengue virus test （ROR of 954.50）， with neither of these signals mentioned in their respective drug instructions. CONCLUSIONS The ADE of romiplostim and eltrombopag mainly affects the blood and lymphatic system， and there are many new suspicious high-risk signals.

Mining and analysis of the ADE signals of avapritinib based on FAERS database / 中国药房

OBJECTIVE To provide reference for clinically safe application of avapritinib. METHODS The adverse drug event （ADE） reports of avapritinib from January 9th，2020，to September 30th，2022 were collected from FDA Adverse Event Reporting System （FAERS） database. For data mining and analysis，reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method in the proportional imbalance method were utilized. RESULTS A total of 10 895 ADE reports with avapritinib as the main suspect drug were gathered，and 201 ADE signals involving 19 systematic organ classifications were found after eliminating invalid signals. The instruction of the drugs did not mention any of the ADE，including tinnitus，dementia，chilly limbs， the reduction of blood iron，the reduction of blood sugar，fever，the reduction of vitamin D and vitamin B12，as well as all ADE in the 2 SOCs of musculoskeletal and connective tissue illnesses，diseases of the reproductive system，and diseases of the breast. The majority of the ADE reports 670 cases with complete drug information were for the nervous system （230 cases，accounting for 34.33%） and ocular organ （277 cases，accounting for 41.34%）. Compared with other systems，daily dose and treatment course showed significant effects on ADE of neurological system and ocular organ （P＜0.05），and the patient’s age had a significant impact on the ADE of the nervous system （P＜0.05）. CONCLUSIONS A greater incidence of ADE after using avapritinib is present in patients older than 65 with a daily dose of 300 mg/d and a treatment period lasting between 31 and 90 days； patients receiving a daily dose of 300 mg/d and a treatment regimen lasting 31 to 90 days are more likely to experience ADE of the ocular organ. Attention should be given to the aberrant symptoms of the patient’s eyes and nervous system throughout clinical use of avapritinib，and prompt intervention should be given.

Mining and analysis of adverse drug event signals related to mepolizumab / 中国药房

OBJECTIVE To provide reference for rational clinical use of mepolizumab. METHODS The reporting odds ratio method and Bayesian confidence propagation neural network method were used to conduct signal mining and analysis of adverse drug event （ADE） reports related to mepolizumab in the United States Food and Drug Administration Adverse Event Reporting System from the first quarter of 2016 to the third quarter of 2022. RESULTS A total of 57 501 ADE reports were extracted with mepolizumab as the primary suspect drug， involving 16 358 patients. Among these reports， the proportion of males （23.51%） was lower than females （50.48%）. The reporting countries were primarily the United States （51.91%） and Canada （29.94%）. Consumers （71.18%） constituted the main reporting population. A total of 172 ADE-positive signals were identified， mainly involving 13 system organ classes such as the respiratory， thoracic and mediastinal disorders （41.63%）， as well as infectious and parasitic diseases （14.16%）. There were 60 high-risk signals， including 15 that were explicitly mentioned or related to adverse reactions in the drug instructions of mepolizumab and 45 signals （such as asthmatic crisis， sputum discoloured， purulent sputum， sleep disorder due to a general medical condition） were newly identified high-risk signals. Among them， 11 high-risk signals exhibited gender or age differences. CONCLUSIONS When clinically using mepolizumab， in addition to the adverse reactions mentioned in the drug instruction， special attention should also be given to changes in the nature of sputum， painful respiration， and sleep disorders.

Data mining for adverse drug reaction signals of daptomycin based on real-world data: a disproportionality analysis of the US Food and Drug Administration adverse event reporting system.

BACKGROUND: Previous reports on daptomycin's adverse drug reactions (ADRs) have been insufficient, often because of limited data. Pharmacovigilance risk signal detection is innovative and has been applied to the safety monitoring and reevaluation of drugs post-marketing. AIM: The study aimed to promote safe daptomycin prescribing by mining and evaluating the daptomycin ADR signals from the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHOD: A disproportionality analysis (reporting odds ratio ROR and proportional reporting ratio PRR) was utilized for FAERS data mining from the first quarter of 2004 to the second quarter of 2021 (the most recent quarterly data at the time of the study). Preferred Terms of ADR reports were categorized by System Organ Class (SOC) based on the Medical Dictionary for Regulatory Activities. RESULTS: This study retrieved 12,221 cases within the reporting period. A total of 140 repetitive signals were obtained by ROR and PRR, of which 53 new ADR signals were not recorded in the drug labels/datasheets. The top three ADR reports were "blood creatine phosphokinase elevation" (ROR, 56.66, 95% confidence interval (CI) 51.07-62.87, PRR 51.94), "eosinophilic pneumonia" (ROR 696.71, 95%CI 603.21-804.70, PRR 657.57), and "rhabdomyolysis" (ROR 22.85, 95%CI 19.94-26.18, PRR 21.83). The highest ROR of "antimicrobial susceptibility test resistant" was found at 9808.14. Reports of rare adverse events, such as "necrotizing fasciitis and compartment syndrome," have emerged. The significant SOCs were "Infections and Infestations" and "Investigations." CONCLUSION: New daptomycin ADR signals were detected. Clinicians should monitor these potential ADRs in patients receiving daptomycin.

Safety Profile of Antipsychotic Drugs: Analysis Based on a Provincial Spontaneous Reporting Systems Database.

Introduction: Antipsychotic drugs are the main therapy for schizophrenia and have been widely used in mental disorder fields. However, the research on the safety of antipsychotic drugs in the real-world is rare. The purpose of this research is to evaluate the safety of antipsychotic drugs based on real-world data. Methods: ADR reports collected by the Henan Adverse Drug Reaction Monitoring Center from 2016 to 2020 were analyzed. We described the safety of antipsychotic drugs by descriptive analysis and four signal mining methods. Meanwhile, the risk factors for serious adverse reactions of antipsychotics were identified. Results: A total of 3363 ADR reports related to antipsychotics were included. We found that the number of adverse drug reaction reports and the proportion of serious adverse reactions have increased year by year from 2016 to 2020. Most adverse drug reactions occurred within 3 months after taking the medicine. The symptoms caused by typical antipsychotics and atypical antipsychotics were different and dyskinesia was more common in typical antipsychotics. Most patients improved or recovered after treatment or intervention while only one patient had sequelae. Low-level hospitals, psychiatric hospitals, youth, and old age could increase the risk of serious adverse reactions. Four off-label signals were found through signal mining, including amisulpride-pollakiuria, ziprasidone-dyspnoea, quetiapine-urinary incontinence, olanzapine-hepatic function abnormal. Conclusion: We found that most ADRs occurred within 3 months after taking the medicine, so close observation was required for patients during the first 3 months of treatment. The ADRs of antipsychotics involved multiple organ-system damages but were not serious. It might be recommended to take alternative drugs after a serious ADR occurred. The symptoms caused by typical APDs and atypical APDs were different. For patients with typical APDs, dyskinesia was more common and should be given special attention. Statistics showed that low-level hospitals, psychiatric hospitals, youth, and old age were risk factors for serious ADRs. The four off-label signals obtained by signal mining should be paid special attention, including amisulpride-pollakiuria, ziprasidone-dyspnoea, quetiapine-urinary incontinence, and olanzapine-hepatic function abnormal.

Data mining of adverse drug reaction of iodine contrast media based on spontaneous reporting system / 中国药房

OBJECTIVE To mine the risk sig nals o f iodine contrast media from spontaneous reporting system. METHODS Reporting odds ratio ，proportional reporting ratio ，Medicines and Healthcare Products Regulatory Agency and Bayesian confidence propagation neural network were used to mine risk signals of 5 iodine contrast media （iopamidol，iohexol，iopromide，ioversol， iodixanol）. RESULTS 1 164（2 446 case times ）adverse drug reaction of iodine contrast media were included ，a total of 14 risk signals involving systems/organs such as respiratory system （3，2，4，3，2 for the above 5 iodine contrast media ）and immune system and 32 specific adverse drug reaction signals including anaphylactic shock ，rash and flushing （11，7，7，3，4 for the above 5 iodine contrast media ）were found in 5 iodine contrast media. CONCLUSIONS The risk signals of 5 iodine contrast media verify that there is a certain correlation between these drugs and above adverse drug reactions. It is suggested that before using iodine contrast media in clinic ，it is necessary to pay attention to whether the patient has a history of tumor and combined medication ，evaluate the patient’s renal function ，and give preventive measures such as hydration in advance. When using iodine contrast media ，it is necessary to pay attention to the temperature ，dose and injection rate. And medical staff need to follow up the patient ’s situation in time after using iodine contrast media to avoiding the impact of delayed adverse reactions.