Organ Class Research Articles

A pharmacovigilance study on the safety of faricimab in real-world scenario using FDA adverse event reporting system database.

Faricimab is predominantlyprescribed for conditions such as age-related macular degeneration (AMD),diabetic macular edema (DME), and macular edema related to retinal veinocclusion (RVO-ME). Currently, a notable absence of large-scale, real-worldstudies focusing on the adverse reactions of faricimab exists. Thisstudy assesses the side effects of faricimab by analyzing reports of adverseevents (AEs) from the FDA's AEReporting System (FAERS) database. Through disproportionality analysis, thisstudy substantiates the drug's safety oversight. Our study revealed 2,746 instances ofadverse events linked to faricimab, spanning 21 system organ classes (SOCs).The study retained 121 significant disproportionality preferred terms (PTs)that met criteria across all four analytical methods. Faricimab-associated AEsnot documented in the drug instructions included visual impairment, blindness,retinal hemorrhage, anterior chamber inflammation, keratic precipitates, dryeye, chorioretinitis, diabetic retinopathy, and others. The majority of our results align withearlier clinical studies and the details outlined in the product's manual. Additionally, we identifiedseveral unforeseen and potential AEsignals related to faricimab use. These insights are instrumental for ongoingclinical surveillance and risk assessment associated with the drug.

Real-world safety of maribavir: a retrospective study based on signal detection in the FDA adverse event reporting system.

Maribavir is a novel antiviral agent targeting cytomegalovirus through inhibition of the UL97 protein kinase, exhibiting a distinct mechanism of action. However, limited data are available on its safety profile post-marketing. This study aimed to evaluate the adverse events (AEs) associated with maribavir using the Food and Drug Administration's Adverse Event Reporting System (FAERS), providing insights to inform clinical practice. We conducted a retrospective analysis of maribavir-related adverse event reports from the FAERS database, spanning the fourth quarter of 2021 to the second quarter of 2024. Signal detection was performed using four statistical methods: the proportional reporting ratio, reporting odds ratio, Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker. A total of 1372 reports associated with maribavir were identified. Seven significant signals emerged at the system organ class level. At the preferred term level, 76 adverse events (AEs) demonstrated positive signals, including novel events such as pleural effusion, hypersomnia, and anosmia, alongside signals related to ear disorders. The majority of AEs were reported within the first month of maribavir use. This study identified several new adverse event signals for maribavir, offering healthcare professionals a deeper understanding of its safety profile, which may guide safer clinical usage.

Post-Marketing Pharmacovigilance of Canakinumab from the FDA Adverse Event Reporting System (FAERS)

Background: Canakinumab, a humanized anti-IL-1β monoclonal antibody, is known for its ability to suppress IL-1β-mediated inflammation. However, continuous monitoring of its safety remains essential. Thus, we comprehensively evaluated the safety signals of canakinumab by data mining from FAERS. Methods: We used a disproportionate analysis to quantify canakinumab-related adverse events (AEs) using four algorithms. Clinical prioritization of the detected signals was assessed with a semiquantitative score method. Serious and non-serious outcomes were compared by statistical methods. Additionally, a stratification analysis of serious infections was conducted at the system organ class (SOC) level. Results: A total of 28,496 canakinumab-related AEs were collected, and 71 suspicious signals detected. Among these, 19 preferred terms (PTs) were identified as unexpected signals, including deafness, appendicitis, brain oedema, cushingoid, cellulitis, and papilledema. Of the AEs, 16 were more likely reported as serious outcomes, such as pneumonia, abdominal pain, deafness, and infection. Based on clinical priority score, 44 PTs were classified as weak, 27 as moderate, and none as strong. Furthermore, 30 PTs demonstrated a high level of evidence, primarily derived from FDA prescribing information, randomized controlled trials, and systematic reviews. Stratification analysis of infections and infestations (serious outcomes) revealed a stronger association of severe infections with canakinumab in older or heavier individuals. All positive signals followed an early failure pattern, with the incidence of canakinumab-associated AEs decreasing over time. Conclusions: We found that most of the suspicious signals were associated with infections. More attention should be paid to serious infections, particularly in males, individuals aged ≥60 years, or those weighing >100 kg, who demonstrated the highest risk of serious infections.

A study on the pharmacovigilance of various SGLT-2 inhibitors

BackgroundSodium-glucose co-transporter two inhibitors (SGLT2is) are widely used in clinical practice due to their proven cardiovascular and renal benefits. However, various adverse drug reactions (ADRs) have been reported. This study aims to systematically update the ADRs associated with SGLT2is and identify the differences among various SGLT2is acovigilance of various SGLT-2 inhibitors.MethodsData from the FAERS database covering Q1 2013 to Q2 2024 were selected for disproportionality analysis. ADRs were defined using the System Organ Classes (SOC) and Preferred Terms (PT) from the MedDRA 27.0 dictionary. Four signal detection metrics—reporting odds ratio (ROR), proportional reporting ratios (PRRs), Bayesian Confidence Propagation Neural Network (BCPNN), and empirical Bayesian geometric mean (EBGM)—were utilized to infer ADRs and assess differences among specific SGLT2i drugs through intersection analysis.ResultsExcept for canagliflozin, both dapagliflozin and empagliflozin showed a general increase in ADRs. Specifically, canagliflozin had 93 ADRs, dapagliflozin had 173, and empagliflozin had 214. Most of these were related to Infections and Infestations, Investigations, and Reproductive System and Breast Disorders, notably manifesting as inflammatory conditions of the urinary and reproductive systems, such as orchitis and testicular abscess, consistent with FDA labeling. Additionally, overlooked ADRs were identified, including bladder cancer, cholangiocarcinoma, and thrombotic strokes, none of which were reported for canagliflozin.DiscussionWhile shared ADRs for SGLT2is are noted in FDA labeling, monitoring for high-risk populations, such as those with cancers or strokes, remains crucial to prevent deterioration. Medication regimens may need adjustment, including selecting canagliflozin or non-SGLT2i alternatives when necessary.

Unveiling the safety profile of lecanemab: A comprehensive analysis of adverse events using FDA adverse event reporting system data.

Lecanemab, a novel monoclonal antibody targeting amyloid-β, has shown promise in treating Alzheimer's disease. Comprehensive post-marketing safety data analysis is crucial to understand its real-world risk profile. This study aimed to evaluate the safety profile of lecanemab using data from the FDA Adverse Event Reporting System (FAERS), with a focus on nervous system disorders and amyloid-related imaging abnormalities. We conducted a disproportionality analysis using the FAERS database to evaluate the safety signals associated with lecanemab. Reporting odds ratio (ROR), proportional reporting ratio, empirical Bayesian geometric mean, and information component were calculated at both system organ class (SOC) and preferred term (PT) levels. Additionally, we performed a time-to-onset analysis using Weibull shape parameter estimation. Analysis at the SOC level revealed significant signals for nervous system disorders (ROR: 7.32, 95% CI: 6.69-8.00). At the PT level, strong signals were observed for amyloid-related imaging abnormalities, particularly those associated with microhemorrhages and oedema (ROR: 4122.81 and 3922.78, respectively). Headache was the most frequently reported adverse event (200 cases), followed by chills (107 cases) and fatigue (97 cases). Time-to-onset analysis showed a median time of 33 days (range: 1-1283) for all adverse events, with neurological events occurring slightly later (median: 42 days, range: 1-1260). Our findings highlight a distinct safety profile for lecanemab, with a predominant impact on the nervous system and a notable association with imaging abnormalities. These results underscore the importance of vigilant monitoring and further research to optimize the risk-benefit profile of lecanemab in clinical practice.

A real-world drug safety surveillance study from the FAERS database of hepatocellular carcinoma patients receiving pembrolizumab alone and plus lenvatinib

Pembrolizumab plus Lenvatinib is regarded as a significant treatment option for advanced unresectable hepatocellular carcinoma (HCC). This study aims to meticulously monitor and identify adverse events (AEs) related to this combined therapy, enhance patient safety, and offer evidence-based recommendations for the appropriate use of these drugs. We gathered adverse drug reactions (ADRs)-related data from the FAERS database for HCC patients who received Pembrolizumab, both alone and in combination with Lenvatinib from the first quarter of 2014 to the fourth quarter of 2023. ADRs signal detection was performed using the ROR, PRR, BCPNN, MHRA, and MGPS methods. We gathered data on 459 and 358 AEs from patients with HCC treated with pembrolizumab alone and in combination with lenvatinib, respectively. Using four signal quantification techniques, we identified 50 and 38 distinct AEs, which were classified into 15 different System organ class (SOC) categories. Notably, the most common AEs associated with pembrolizumab were gastrointestinal disorders and hepatobiliary disorders. In both patient groups, the most frequently reported AEs were hepatic encephalopathy, blood bilirubin increased and diarrhea. We also observed some unexpected significant AEs, such as dehydration, skin ulcers, and intestinal perforation. The countries reporting the highest number of AEs were the United States, followed by China, France, and Japan. The median onset time for AEs related to pembrolizumab alone and its combination with lenvatinib was 80.5 days (interquartile range 20.0–217.3 days) and 77.5 days (interquartile range 19.7–212.3 days), respectively. This study offers new insights into the monitoring and management of ADRs in HCC patients receiving pembrolizumab alone or in combination with lenvatinib. It is crucial to closely monitor the safety of this treatment regimen in HCC patients to avoid serious AEs.

Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).

Is there an association between dydrogesterone exposure during early pregnancy and the reporting of birth defects? This observational analysis based on global safety data showed an increased reporting of birth defects, mainly hypospadias and congenital heart defects (CHD), in pregnancies exposed to dydrogesterone, especially when comparing to progesterone. Intravaginal administration of progesterone is the standard of care to overcome luteal phase progesterone deficiency induced by ovarian stimulation in ART. In recent years, randomized controlled clinical trials demonstrated that oral dydrogesterone was non-inferior for pregnancy rate at 12 weeks of gestation and could be an alternative to micronized vaginal progesterone. Safety profiles in both mother and child were similar. However, concerns have been raised regarding an association between dydrogesterone usage during early pregnancy and CHD in offspring. We performed a disproportionality analysis, also called case-non-case study, similar in concept to case-control studies, using the WHO global safety database, VigiBase. The study cohort consisted of individual pregnancy-related safety reports, using the ad hoc standardized query (SMQ 'Pregnancy and neonatal topics'). Cases of birth defects consisted of safety reports containing terms related to the 'congenital, familial and genetic disorders' System Organ Class from the Medical Dictionary for Regulatory Activities. Non-cases consisted of safety reports containing any other adverse event, in pregnancy-related safety reports. Considering reports since database inception to 31 December 2021, we first compared the reporting of birth defects with dydrogesterone to that of any other drug on the database, then to any other drug used for ART. Secondly, we performed a comparison on the reporting of birth defects for dydrogesterone with progesterone. Results are presented as reporting odds ratio (ROR) and their 95% CI. For each comparison, two sensitivity analyses were performed. Finally, a case-by-case review was performed to further characterize major birth defects and sort anomalies according to classification of EUROCAT. Study cohort consisted of 362 183 safety reports in pregnant women, among which 50 653 reports were related to the use of drugs for ART, including 145 with dydrogesterone and 1222 with progesterone. Of these, 374 (0.7%) were cases of birth defects: 60 with dydrogesterone and 141 with progesterone, including 48 and 92 cases compatible with major birth defect cases according to EUROCAT classification, respectively. Major birth defects reported with dydrogesterone were mainly genital defects such as hypospadias and CHD. A significantly higher disproportionate reporting of birth defects was found with dydrogesterone when compared to any other drug (ROR 5.4, 95% CI [3.9-7.5]), to any other ART drug (ROR 6.0, 95% CI [4.2-8.5]), and to progesterone (ROR 5.4, 95% CI [3.7-7.9]). Sensitivity analyses found consistent results. First, under-reporting, being inherent to pharmacovigilance systems, impedes the measurement of the incidence of adverse drug reactions and can limit the sensitivity of signal detection. Second, drug causality, not being the same for all cases, is challenging for such events and requires further assessment. However, sensitivity analyses showed consistent results. This possible safety signal emphasizes the need for further investigation regarding the fetal safety profile of dydrogesterone. No funding was received for this study. None of the authors have any financial and personal relationships with other people or organizations that could influence the design, conductor or reporting of this work. N/A.

Detection of risk signals for ustekinumab in the real world using the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Ustekinumab is a fully human interleukin-12/23 (p40) inhibitor used to treat immune-mediated diseases. However, the limitations of clinical trials and the expanding target population necessitate an update on the ustekinumab-associated adverse events (AEs). We conducted signal mining for ustekinumab-related AEs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Research Design and Methods AE reports were collected from 2009 Q3 to 2024 Q1. Four disproportionality analysis algorithms – reporting odds ratio, medicines and healthcare products regulatory agency, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker – were used to quantify the signals of ustekinumab. Results During this period 69,345 AE reports associated with ustekinumab were collected, and ustekinumab was identified as the primary suspect. Overall, 319 signals involving 15 system organ classes were identified, and 111 signals had a medium or strong value for IC025. Of them, 67 were classified as important medical events. Squamous cell carcinoma, pertussis, vulval abscess, breast abscess, and fistula exhibited higher signal intensities. Conclusions Our study identified the risk signals for ustekinumab using real-world data and provides further evidence to support its rational use. Due to the limitations of FAERS, further studies are warranted to verify these findings.

Analyzing the adverse events of NK-1 receptor antagonists: a pharmacovigilance study from the FAERS database

BackgroundNK-1 receptor antagonists (NK-1RAs) are proven to be successful in preventing chemotherapy-induced nausea and vomiting (CINV). The safety profile of NK-1RAs has not been systematically analyzed in the real world. This pharmacovigilance study investigated the differences in adverse events (AEs) between NK-1RAs.MethodsAdverse events (AEs) associated with NK-1RAs were gathered and standardized using data from the FAERS database spanning from the first quarter of 2009 to the fourth quarter of 2023. Various disproportionality techniques were employed for data analysis, such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).ResultsA total of 5434AE reports listing NK-1RAs as the primary suspected drugs were identified. The System Organ Classes (SOC) appeared as significant safety signals were found. Among NK-1RAs, the most frequently reported AEs were related to general disorders and administration site conditions. In terms of PT level, the strong signals were mainly injection site reactions associated with aprepitant and fosaprepitant. Moreover, toxic encephalopathy and encephalopathy of the aprepitant were all positive with four algorithms. A significant finding was the recognition of adverse events linked to endocrine disorders, which were not previously mentioned in the medication instructions.ConclusionThe safety profile of NK-1RAs has been reported to be variable.If intravenous formulations were used in the clinic, injection site reactions should be a concern. In addition, more attention should be paid to the management of encephalopathy toxicity in patients treated with aprepitant in combination with ifosfamide. Besides known AEs, we have identified several new high-risk AEs, such as inappropriate antidiuretic hormone secretion, adrenal insufficiency and hyponatraemia. Overall, clinicians should closely monitor the occurrence of NK-1RA-related AEs in clinical applications.

Safety assessment of ezetimibe: real-world adverse event analysis from the FAERS database

ABSTRACT Background Ezetimibe is known for its lipid-lowering safety and tolerability, but its real-world adverse effects have not been fully evaluated. In this study, adverse events associated with ezetimibe were investigated using the FAERS database for the period 2004 to 2023. Research design and methods Adverse events data for ezetimibe, spanning from the first quarter of 2004 to the fourth quarter of 2023, were standardized and analyzed using signal quantification methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (EBGM). Results Among 11,550 adverse drug events reports with ezetimibe as the primary suspect drug, 211 preferred terms (PTs) were identified across 24 different system organ classes (SOCs).Notably, in addition to the adverse reactions already specified in the instruction manual, unstable angina (n = 120, ROR 30.53(25.47-36.58), PRR 30.41(25.49-36.28), IC 4.9(4.64), EBGM 29.85(25.66)), crush syndrome(n = 19,ROR 298.83(182.95-488.09), PRR 298.65(182.96-487.49), IC 7.97(7.29),EBGM 251.12(166.57)), and autoscopy (n = 7, ROR 28.81(13.64-60.85), PRR 28.80(13.68-60.65), IC 4.82(3.81), EBGM 28.30(15.14))were new adverse reactions that emerged as strong signals. Conclusions Ezetimibe is effective in lowering blood lipids, but there is a risk of adverse reactions such as unstable angina, rhabdomyolysis and autoscopy, which require careful monitoring by physicians.

Safety assessment of deutetrabenazine: real-world adverse event analysis from the FAERS database

BackgroundDeutetrabenazine is a widely used drug for the treatment of tardive dyskinesia (TD), and post-marketing testing is important. There is a lack of real-world, large-sample safety studies of deutetrabenazine. In this study, a pharmacovigilance analysis of deutetrabenazine was performed based on the FDA Adverse Event Reporting System (FAERS) database to evaluate its relevant safety signals for clinical reference.MethodsAdverse events (AEs) of FAERS with deutetrabenazine as the primary suspect drug were collected from the first quarter (Q1) of 2017 to Q1 of 2024. Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to mine AEs risk signals of deutetrabenazine. AEs were standardized and classified using the System Organ Class (SOC) and Preferred Terms (PTs) from Medical Dictionary for Regulatory Activities (MedDRA) version 23.0.ResultsA total of 3,583 AEs with deutetrabenazine as the primary suspect drug were collected in this study. We found that these AEs involved 23 SOCs, and the positive signals were mainly concentrated in systemic disease and various reactions at the site of administration (n = 1816, ROR = 1.23, PRR = 1.18, IC = 0.24, EBGM = 1.18), neurological disorders (n = 1736, ROR = 3.02, PRR = 2.60, IC = 1.38, EBGM = 2.60) and psychiatric disorders (n = 1,659, ROR = 4.15, PRR = 3.52, IC = 1.82, EBGM = 3.52). We eventually identified 100 valid PTs that met the criteria of the four algorithms. Drug ineffective, dyskinesia, depression, somnolence, suicidal ideation were considered to be the common PTs of deutetrabenazine. Tongue thrust (n = 4, ROR 253.47, PRR 253.35, IC 7.88, EBGM 235.95), grunting (n = 5, ROR 78.49, PRR 78.45, IC 6.26, EBGM 76.71) and drooling (n = 17, ROR 13.21, PRR 13.19, IC 3.72, EBGM 13.14) were not mentioned in the specification, but the high signal intensity suggested that they may be the potential adverse reactions.ConclusionThe efficacy of deutetrabenazine may be accompanied by some potential adverse effects in several systems. Adverse events in psychiatric, neurologic, gastrointestinal and respiratory need to be monitored in clinical practice.

A real-world pharmacovigilance analysis for agalsidase beta: findings from the FDA adverse event reporting database

ABSTRACT Background Fabry disease (FD), an X-linked lysosomal disorder, is marked by a lack of alpha-galactosidase A (α-Gal A). Agalsidase beta, a recombinant form of α-Gal A, is fundamental to enzyme replacement therapy for FD but requires close monitoring for adverse events (AEs). Research Design and Methods This study retrospectively analyzed the Food and Drug Administration Adverse Event Reporting System (FAERS) database for agalsidase beta-related AEs. Disproportionality analysis was used for data analysis. Results A total of 7,611 AE reports for agalsidase beta were analyzed. The most common AEs included pyrexia, pain, chills, malaise, and nausea. Several system organ classes including Cardiac Disorders, General Disorders and Administration Site Conditions, and Vascular Disorders, showed positive signals. Subgroup analysis by gender revealed differences in AE reporting, with males exhibiting a higher reporting odds ratio for certain preferred terms such as Renal Transplant and Drug Specific Antibody Present. Conclusion The FAERS database analysis of agalsidase beta AEs identified a significant number of cardiovascular, renal, and cerebrovascular system-related reports. While agalsidase beta is generally well-tolerated, the study underscores the necessity for gender-specific treatment approaches due to the higher incidence of certain AEs in males.

Adverse event of ruxolitinib cream: a real-world analysis based on FDA adverse event reporting system from 2021 to 2024

ABSTRACT Background Ruxolitinib cream, a topical Janus kinase (JAK) inhibitor, is a widely used treatment for various dermatological diseases. This study employs the FDA Adverse Event Reporting System (FAERS) database to examine adverse events (AEs) associated with ruxolitinib cream. Methods This study employed disproportionate analysis methods, including reported odds ratio and proportional reporting ratio, to collate AEs reported from the fourth quarter of 2021 to the first quarter of 2024. Results After data processing, 803 reports involving ruxolitinib cream were analyzed. Statistically significant signals were identified for 4 system organ classes (SOCs) and 29 preferred terms (PTs). The most notable signal observed in the SOCs was associated with skin and subcutaneous tissue disorders. For PTs, the AEs observed included clinical symptoms such as pruritus, skin irritation, and burning sensations, as well as signs such as rash, scratching, erythema, and dry skin. Additionally, other observed AEs included diseases such as acne, drug hypersensitivity, and herpes zoster. Conclusions This study offers insights into the safety of ruxolitinib cream, improving understanding of its AEs and guiding safer clinical practices. However, the FAERS database lacks data on AE severity and the ability to establish causality, requiring further research to clarify mechanisms behind certain AEs.

Real-world study of isavuconazole adverse events based on pharmacovigilance spontaneous reporting systems

ABSTRACT Background Isavuconazole is a novel second-generation triazole antifungal agent.We conducted a retrospective investigation to analyze the occurrence of adverse events (AEs) associated with isavuconazole in real-world clinical use by data-mining self-reporting databases, aiming to provide comprehensive data for its safe and effective clinical application. Research design and methods All data obtained from the VigiBase, the EudraVigilance and the FAERS database. In the FAERS database, data mining algorithms, including reporting odds ratio (ROR) and proportional reporting ratio (PRR), were utilized to detect adverse event (AE) signals. Results A total of 4,105 AE reports related to isavuconazole were retrieved from these databases. The highest proportion of AE reports was observed in individuals aged between 18–64 years old. The general disorders and administration site conditions system organ class accounted for the largest number of reported cases. The system organ classes with most signals and reports included general disorders and administration site conditions, blood and lymphatic system disorders as well as investigations related to hepatobiliary disorders. Notably high ROR and PRR values were observed for AE signals associated with hepatobiliary disorders. Conclusion Isavuconazole has fewer interactions and less liver, kidney and cardiac toxicity than other triazole antibiotics. The identification of novel AEs necessitates meticulous attention and further investigation and analysis.

Signal detection and analysis of sulfasalazine adverse reaction events based on the US FDA adverse event reporting database

ABSTRACT Background Based on real data from the FDA Adverse Event Reporting System (FAERS), we explored and evaluated the adverse reactions (ADRs) of sulfasalazine (SSZ) in the first quarter of 2004–2023 to provide a reference basis and early warning for the safe use of SSZ in the clinic. Research design and methods The reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM) were used as measures of SSZ-associated adverse events (AEs) signals, mining for potential positive signals between SSZ and AE. Results In this study, a total of 5327 case reports related to SSZ in the last 20 years involving 25 system organ classes (SOCs) were collected in FAERS. The AEs of SSZ were mainly focused on Immune system disorders (n = 1621, IC025 = 2.86), Blood and lymphatic system disorders (n = 638, IC025 = 2.4), and others. In addition, we found 41 adverse reactions not mentioned in the specification, including oculomucocutaneous syndrome (n = 12, IC025 = 4.86), wegener’s granulomatosis(n = 6, IC025 = 4.05) and reproductive system aspects. Conclusion Significant new AEs signals were observed in this study and may provide important support for clinical monitoring and risk identification in SSZ.

Postmarketing Safety Surveillance of Topiramate: A Signal Detection and Analysis Study Based on the FDA Adverse Event Reporting System Database.

This study aims to investigate the occurrence of adverse events associated with topiramate by analyzing data from the FDA Adverse Event Reporting System. The goal is to provide a basis for the safe clinical use of topiramate. Adverse event data from the FDA Adverse Event Reporting System, from its inception through the first quarter of 2024, were extracted. Signal detection was conducted using three methods: the reporting odds ratio, the medicines and healthcare products regulatory agency method, and the Bayesian confidence propagation neural network. Adverse events were statistically analyzed according to the preferred term and system organ class classifications from the Medical Dictionary for Regulatory Activities version 27.0. Positive signals were then compared against the drug label and the Important Medical Event list. A total of 12,168 adverse event reports involving topiramate as the primary suspect were analyzed, resulting in the extraction of 244 positive signals across 15 system organ classes. Among these, 21 signals were identified as serious adverse reactions not included in the drug label, encompassing 5 system organ classes. Notable signals included hypospadias, spina bifida, abortion spontaneous, renal tubular dysfunction, uveitis, retinal detachment, and choroidal effusion. Additionally, signals such as osmotic demyelination syndrome and Arnold-Chiari malformation were identified as requiring further monitoring. This study identified several unexpected and serious adverse reaction signals that align with previously reported cases. These findings underscore the need for ongoing study, focused attention, and vigilant monitoring during the clinical use of topiramate.

Safety of talimogene laherparepvec: a real‐world retrospective pharmacovigilance study based on FDA Adverse Event Reporting System (FAERS)

BackgroundOncolytic virus therapy is a rapidly evolving emerging approach for the medical management of cancer. Talimogene laherparepvec (T-VEC) is the first and only Food and Drug Administration (FDA)-approved oncolytic virus therapy. Considering that exactly how T-VEC works is not known, there is a strong need for a comprehensive pharmacovigilance study to identify safety signals of potential risks with T-VEC.ObjectiveThe objective of this study was to assess the risk of adverse events (AEs) related to T-VEC.MethodsWe implemented a pharmacovigilance study utilizing individual case safety reports (ICSRs) reported to the FDA Adverse Event Reporting System (FAERS) database dated from 2004 quarter 1 to 2023 quarter 3. In this study, we used two algorithms, reporting odds ratio (ROR) and information component (IC), to assess the risk of AEs related to T-VEC.ResultsA total of 1138 ICSRs of patients who received the T-VEC and reported to the FDA dated from 2004 quarter 1 to 2023 quarter 3 were available. A total of seven system organ classes (SOCs) demonstrated statistically significant signals, i.e. General disorders and administration site conditions, Injury, poisoning and procedural complication, Infections and infestations, Neoplasms benign, malignant and unspecified, Skin and subcutaneous tissue disorders, Hepatobiliary disorders, and Endocrine disorders. From the preferred term level perspective, the most reported AEs in T-VEC-treated patients were pyrexia, illness, influenza, influenza-like illness, and chills. Unexpected significant AEs were detected, such as sepsis, encephalitis, syncope, and lymphadenopathy.ConclusionsMost AEs in T-VEC-treated patients have been previously mentioned in the prescriptive information or documented in other clinical trials. But safety signals were also be detected in 4 unexpected AEs (sepsis, encephalitis, syncope, and lymphadenopathy). Further clinical trials need to be undertaken to facilitate a more comprehensive comprehension of the safety profile of T-VEC.

Safety assessment of tafamidis: a real-world adverse event analysis from the FAERS database

ABSTRACT Background Tafamidis emerged as the first FDA-approved drug for treating termed amyloid fibrils. This study aims to analyze adverse events (AEs) related to tafamidis from the second quarter (Q2) of 2019 to the fourth quarter (Q4) of 2023 from the FDA adverse event reporting system (FAERS) database. Research design and methods The AE data related to tafamidis from 2019 Q2 to 2023 Q4 were collected and standardized. Various signal quantification techniques, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker, were employed for analysis. Results Among the 8742 AE reports with tafamidis as the primary suspected drug, 180 preferred terms of AEs spanning 27 different system organ classes were identified. Unique adverse events to tafamidis included renal and urinary disorders and ear and labyrinth disorders, with not mentioned in the official drug label. Additionally, uncommon but significantly strong AE signals, such as blood culture positive and acquired hemophilia, were observed. Common AEs with relatively high occurrence rates included death, off-label use, fall, hypoacusis, and dysphagia. Conclusion These findings offer valuable insights for optimizing the use of tafamidis and reducing potential side effects, thereby facilitating its safe use in clinical settings.

A disproportionality analysis of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Objective The FDA Adverse Event Reporting System (FAERS) was used to mine and evaluate adverse events (AEs) associated with cyclin-dependent kinase (CDK) 4/6 inhibitors, thereby providing a reference for clinical rational drug use. Methods AE data related to CDK4/6 inhibitors from the first quarter of 2015 to the first quarter of 2023 were acquired from FAERS, while the signal mining was processed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. Results The number of AE reports for CDK4/6 inhibitors was, respectively, 132,494 for palbociclib, 56,151 for ribociclib, and 7,014 for abemaciclib. The corresponding numbers of AE signals were 322,522, and 59, with the number of involved System Organ Class (SOC) being 23, 23, and 15, mainly involving blood and lymphatic system disorders, respiratory, thoracic and mediastinal disorders, hepatobiliary disorders, skin and subcutaneous tissue disorders, etc. Conclusion CDK4/6 inhibitors could lead to pulmonary toxicity, myelosuppression, skin reactions, etc. Special attention should be paid to abemaciclib for interstitial lung disease (ILD), erythema multiforme, and thrombosis risk; ribociclib for cardiac toxicity, hepatotoxicity, and musculoskeletal toxicity; palbociclib for neurocognitive impairment and osteonecrosis of the jaw.

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)

ABSTRACT Objective Given the extensive use of atorvastatin in managing cardiovascular conditions and the surge in reported adverse drug reactions (ADRs), this study leverages the FAERS database to comprehensively evaluate atorvastatin-associated adverse events, thereby enhancing our understanding of its safety profile in real-world settings. Methods A retrospective observational pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q1 2024. Four algorithms – ROR, PRR, BCPNN, and EBGM – were employed to detect signals of adverse events (AEs) linked to atorvastatin through disproportionality analysis. Results Out of 17,627,340 reports in the FAERS database 81,955 involved atorvastatin. Consistently identified AEs across all four algorithms included musculoskeletal and connective tissue disorders, metabolic and nutritional disorders, and hepatobiliary disorders at the system organ class (SOC) level. A total of 4,575 significant disproportionate preferred terms (PTs) were observed across 23 SOCs, with key PTs being ‘immune-mediated myositis,’ ‘type 2 diabetes mellitus,’ ‘necrotizing myositis,’ ‘autoimmune myositis,’ and ‘myopathy.’ Additionally, unexpected AEs such as erectile dysfunction were identified. The median onset time for these AEs was 60 days, with most occurring within the first 30 days of treatment. Conclusion This study identified both expected and unexpected AEs associated with atorvastatin, highlighting the need for continued surveillance and providing valuable insights for clinicians to optimize atorvastatin use and address safety concerns.