Adverse Event Reporting Research Articles

Infection toxicity assessment of tumor necrosis factor α inhibitors in the treatment of IBD: a real-world study based on the US food and drug administration adverse events reporting system (FAERS)

ABSTRACT Background Tumor necrosis factor α (TNF-α) inhibitors are widely used to treat inflammatory bowel disease (IBD), but systematic risk assessment of infectious toxicity is still lacking. Research design and methods We used disproportional analysis to calculate infection-related risk signals for four TNF-α inhibitors and compared them with infection-related signals for seven other therapies. Results There were 55,379 reports of infection-related adverse events (AEs) with TNF-α inhibitors as a ‘primary suspect (PS)’ therapy. The median time to onset of infection-related AEs was 113 days (interquartile range [IQR] 14–612). TNF-α inhibitors present the strongest infectious toxic signal than interleukin 12/23 (IL-12/23) inhibitors, integrin blockers, Jak inhibitors, and S1P receptor modulator. Compared with infliximab, certolizumab pegol, and adalimumab, golimumab showed the strongest signal. The strongest signal corresponding to appendicitis, pulmonary tuberculosis, pneumonia, sepsis, urinary tract infection, otitis media and herpes zoster is golimumab, infliximab, golimumab, natalizumab, certolizumab pegol, infliximab, and infliximab. Conclusions Compared with other control therapies, TNF-α inhibitors have the strongest infectious toxicity signal. Compared with other TNF-α inhibitors, golimumab has the strongest infectious toxicity signal. When using TNF-α inhibitors to treat IBD, infection-related AEs should be vigilant.

Adverse event profiles of four monomethyl auristatin E-conjugated antibody drug conjugates: a disproportionality analysis based on the US FDA adverse event reporting system (FAERS) database

ABSTRACT Background Antibody-drug conjugates (ADCs) with monomethyl auristatin E (MMAE) have recently become prevalent in cancer treatment. This study aimed to comprehensively examine the adverse events (AEs) associated with regulatory-approved MMAE-conjugated ADCs using the FDA Adverse Event Reporting System (FAERS). Research design and methods A disproportionality analysis of reports from July 2011 to September 2024 was conducted to detect AE signals in adult patients with cancer receiving any of the four MMAE-conjugated ADCs (brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and tisotumab vedotin) using reporting odds ratio and information component. Results FAERS yielded 12,655 reported cases with 4,958 drug-AE pairs. Positive signals observed across the four MMAE-ADCs included ‘blood and lymphatic system disorders’ and ‘metabolism and nutrition disorders’ at the system organ class, and anemia, febrile neutropenia, hypokalemia, peripheral neuropathy, and pneumonitis for individual AEs, with 54 other overlapping AEs shared by at least three of the ADCs. Conclusions FAERS analysis revealed overlapping safety signals in MMAE-conjugated ADCs. Although further research is necessary to clarify causal relationships, our findings provide a basis for understanding the characteristics of possible AEs in MMAE-ADCs, aiding clinical decision-making for patient safety management.

Real-world data and Mendelian randomization analysis in assessing adverse reactions of rilonacept.

Rilonacept, an interleukin-1 (IL-1) "trap," is FDA-approved for recurrent pericarditis, but research on its adverse reactions is limited due to its recent introduction. This study aimed to identify potential adverse reactions associated with rilonacept using the FDA Adverse Event Reporting System (FAERS) and to evaluate long-term effects through Mendelian randomization (MR) analysis. We analyzed all adverse event reports related to rilonacept from the FAERS database between January 2021 and June 2024. Positive signals for adverse reactions were extracted using reporting odds ratios (ROR) and information components (IC). MR analysis was conducted using genetic variants as instrumental variables to explore causal relationships between rilonacept and identified adverse reactions, with sensitivity analyses performed for robustness. A total of 419 adverse event reports were analyzed, documenting 1847 AEs. Common events included COVID-19, injection site rash, pain, and injection site reaction, categorized into 27 System Organ Classes (SOCs). Notable frequencies were found in Infections and Infestations, Nervous System Disorders, and Skin and Subcutaneous Tissue Disorders. Disproportionality analysis identified positive signals primarily in Skin and Subcutaneous Tissue Disorders, Cardiac Disorders, and Immune System Disorders, with 11 AEs showing positive signals in both Preferred Terms (PTs) and SOCs. MR analysis revealed significant associations between IL-1RN (rilonacept) and allergic urticaria (OR: 1.56), rash (OR: 0.64), and myocarditis (OR: 2.26). Rilonacept is effective for certain inflammatory conditions, but careful monitoring for adverse reactions, particularly involving the immune system, skin, and cardiac issues, is essential.

Descriptive Analysis of Reported Adverse Events Associated with Vitiligo Medications Using FDA Adverse Event Reporting System (FAERS) Databases 2013–2023

Vitiligo, an autoimmune disorder causing depigmented skin patches, includes two types, segmental (SV) and non-segmental (NSV). Previously, NSV was off-label treated using Calcineurine inhibitors (Tacrolimus and Pimecrolimus). In 2022, the FDA approved Ruxolitinib cream, targeting the JAK/STAT pathway for NSV treatment based on promising results. This research conducts a retrospective descriptive safety assessment of Tacrolimus, Pimecrolimus, and Ruxolitinib safety in vitiligo treatment, utilizing the FDA Adverse Event Reporting System (FAERS) database spanning the period from 2013 to 2023 and including patients aged 2 years and above, encompassing both brand and generic names. A total of 844 adverse event reports involving 388 patients were extracted and categorized into dermatological and systemic groups for analysis. Tacrolimus resulted in 12 hospitalizations, two life-threatening events, and four disabilities. Pimecrolimus exhibited urticaria and pigmentation disorders, with tooth fracture as the primary systemic event. Pericarditis was the predominant systemic side effect of Ruxolitinib, followed by anemia, headache, and urosepsis. Local dermatological side effects reported were generally mild, not warranting treatment cessation. In conclusion, vitiligo significantly impacts patients’ psychological well-being, necessitating continuous post-marketing safety monitoring for topical medications.

Pharmacovigilance insights into drug-associated venous thromboembolism.

Venous thromboembolism (VTE), affecting 1-2 per 1,000 adults annually, represents a major preventable cause of hospitalization and mortality. The use of specific medications is an acquired risk factor for VTE. This pharmacovigilance study systematically evaluated medication-associated VTE risk using the largest publicly available adverse event database. Disproportionality analysis of adverse event reports from the US Food and Drug Administration Adverse Event Reporting System was conducted between 2004 Q1 and 2024 Q3. Medications were stratified by Anatomical Therapeutic Chemical classification, with time-to-event analysis using Weibull distribution modeling (shape parameter β). There were 168,960 reports associated with drug-associated VTE, encompassing 1,718 medications. Of the 135 medications identified by disproportionality analysis as having a significant risk, 58 did not mention VTE in their package inserts. Antineoplastic and immunomodulating agents were found to have the largest number (64, 47.4%), followed by genito-urinary system and sex hormones (34, 25.2%), and blood and blood forming organs (16, 11.9%). The shape parameter β of all cases was 0.649 (95% CI: 0.643-0.656), indicating an early failure pattern. The shortest drug-associated times were observed with andexanet alfa, recombinant FVIIa, and basiliximab. Females (55%) and the 45-64 age group (34%) were predominantly affected. Reports and deaths due to drug-associated VTE have increased over the years. A total of 135 medications showed positive signals for VTE (58 unmentioned in package inserts). The high-risk profile of anti-tumor agents and immunomodulators was highlighted. These findings provide robust data-driven guidance for clinical pharmacotherapy to mitigate VTE risks.

Cardiovascular toxicities associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a pharmacovigilance study based on FDA adverse event reporting system.

Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) are widely used in the treatment of various cancers. However, post-marketing evidence regarding their cardiovascular toxicities remains limited. This pharmacovigilance study aimed to comprehensively evaluate the association between VEGFR-TKIs and cardiovascular toxicities in cancer patients. We retrieved and analyzed cardiovascular toxicity reports related to VEGFR-TKIs from the FDA Adverse Event Reporting System (FAERS). Disproportionality analyses were performed using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM) to detect safety signals of cardiovascular toxicities associated with VEGFR-TKIs. A total of 12,726 cancer patients experienced cardiovascular toxicities associated with VEGFR-TKI treatment. All eleven VEGFR-TKIs were associated with cardiovascular toxicities, with hypertension being the most consistently reported event across all agents. Among them, cabozantinib was associated with the highest number of cardiovascular events, whereas lenvatinib exhibited the strongest signal. Notably, lenvatinib was associated with cardiac failure (ROR = 2.521, PRR = 2.479, IC = 1.308, EBGM = 2.476) and cardiomyopathy (ROR = 2.801, PRR = 2.788, IC = 1.476, EBGM = 2.782); sunitinib with cardiac failure (ROR = 2.745, PRR = 2.693, IC = 1.426, EBGM = 2.687) and cardiomyopathy (ROR = 3.020, PRR = 3.004, IC = 1.584, EBGM = 2.997); ponatinib with cardiomyopathy (ROR = 3.393, PRR = 3.372, IC = 1.752, EBGM = 3.368); and vandetanib with Torsade de pointes/QT prolongation (ROR = 27.930, PRR = 26.101, IC = 4.703, EBGM = 26.051). VEGFR-TKIs were associated with cardiovascular toxicities, particularly hypertension. Notably, lenvatinib and sunitinib were associated with cardiac failure and cardiomyopathy, ponatinib with cardiomyopathy, and vandetanib with Torsade de pointes and QT prolongation. Future prospective studies are warranted to further clarify the causal relationships between these agents and cardiovascular toxicities.

Illuminating the shadows - perspectives on mRNA vaccine adverse events - mechanisms, risks and management]: A review.

Illuminating the shadows - perspectives on mRNA vaccine adverse events - mechanisms, risks and management]: A review.

Drugs Associated With Floppy Iris Syndrome: A Real-World Population-Based Study.

Drugs Associated With Floppy Iris Syndrome: A Real-World Population-Based Study.

H1 antihistamine-induced adverse events and time to onset: Aretrospective analysis using the Japanese Adverse Drug Event ReportDatabase.

H1 antihistamines have not been systematically evaluated for adverse events (AEs) in real-world settings despite their widespread use in Japan. We investigated the characteristics of AEs caused by H1 antihistamines using the Japanese Adverse Drug Event Report (JADER) database. We extracted 14 common AEs (including similar AEs) with a high frequency from the JADER database (April 2004 ‒ September 2023) for patients taking H1 antihistamines as "suspected drugs". Adjusted reporting odds ratios (aRORs) for sex and age were calculated to identify possible H1 antihistamines. A time-event analysis was performed using a Weibull distribution. Among the 32,592 case reports where H1 antihistamines were identified as "suspected drugs", a total of 9,549 case reports involving 2,881 patients were extracted for the common 14 AEs associated with 6 first-generation and 16 second-generation drugs. Among these patients, 53.6% were female, and patients aged 50-79 years had a high incidence (45.7%). The highest aROR was for alopecia (56.6), followed by angioedema (3.2), hepatotoxicity (2.6), loss of consciousness (2.4), and Stevens-Johnson syndrome (2.1). Anaphylaxis, Stevens-Johnson syndrome, drug/toxic eruption, angioedema, and convulsions/epilepsy occurred within 1 week of H1 antihistamine use. Hepatotoxicity, loss of consciousness, convulsion/epilepsy, pneumonia and aplastic anemia occurred over time throughout H1 antihistamine treatment. The shape parameter β values of most AEs were <1.0. This study revealed that most severe AEs, such as anaphylaxis and toxic cutaneous diseases, caused by H1 antihistamines occurred within 1 week of treatment. Hepatotoxicity, alopecia, interstitial pneumonia, and aplastic anemia occurred throughout the treatment period.

Vitiligo development following COVID-19 vaccination: A retrospective analysis of 128 cases using the Vaccine Adverse Events Reporting System.

Vitiligo development following COVID-19 vaccination: A retrospective analysis of 128 cases using the Vaccine Adverse Events Reporting System.

Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study.

Unravelling the cardioprotective effects of calcitriol in Sunitinib-induced toxicity: A comprehensive in silico and in vitro study.

Disproportionality analysis and risk factor assessment of drug-associated thyroid dysfunction adverse events: a study based on the FAERS database.

Thyroid dysfunction (TD) is a common adverse event (AE) associated with various pharmacological agents. However, comprehensive real-world evaluations of drug-associated TD AEs remain limited. This study utilized the U.S. FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2024 to perform analysis. The reporting odds ratio (ROR) method was calculated to detect signals of TD AEs, including hyperthyroidism and hypothyroidism. Chi-square tests, Bonferroni correction, and LASSO regression were employed to select relevant predictors of TD AEs, which were subsequently analyzed using multivariate logistic regression to assess their independent associations. A total of 46,725 reports with TD AEs, of which 18,057 were hyperthyroidism and 28,668 were hypothyroidism. The results indicated that 21 drugs met the univariate screening criteria for hyperthyroidism, while 36 drugs were identified as meeting the criteria for hypothyroidism. Most of the drugs associated with TD AEs were antineoplastic agents. Multivariate analysis revealed that female patients were more likely to experience drug-associated TD AEs. In addition, 20 drugs were identified as significant factors associated with hyperthyroidism, while 34 drugs were associated with hypothyroidism. This study identified both known and previously unrecognized drug associations with TD AEs, particularly involving antineoplastic agents. The findings underscore the importance of routine thyroid monitoring during high-risk therapies and highlight the value of real-world pharmacovigilance in detecting emerging safety signals.

Reported psychiatric adverse events among isotretinoin users: Monitoring priorities from a 20-year FDA Adverse Event Reporting System database study.

Reported psychiatric adverse events among isotretinoin users: Monitoring priorities from a 20-year FDA Adverse Event Reporting System database study.

Disproportionality analysis of progestogens and estrogens demonstrates increased meningioma risk.

Disproportionality analysis of progestogens and estrogens demonstrates increased meningioma risk.

Pharmacovigilance insights into antibody–drug conjugates: a multi-database analysis of adverse events in leukemia treatment

ABSTRACT Background Gemtuzumab ozogamicin and inotuzumab ozogamicin play a crucial role in leukemia treatment. This study aims to explore multiple databases to identify adverse event (AE) signals that could enhance the safe use of these drugs. Methods design and methods The FDA Adverse Event Reporting System (FAERS) database ASCII packages, covering 83 quarters from Q1 2004 to Q3 2024, were imported into SAS software (version 9.4) for data cleaning and analysis. Signal detection methods included the ROR, PRR, BCPNN and MGPS. The Japanese Adverse Drug Event Report database (JADER) and WHO Adverse Drug Event Report database (VigiAccess) were used to validate the results. Results In FAERS and VigiAccess, the most frequent positive PT signal for gemtuzumab ozogamicin was ‘febrile neutropenia.’ In FAERS, the most frequent positive PT signal for inotuzumab ozogamicin was ‘death.’ The top five PTs with the highest signal intensity for both drugs across the three databases consistently included ‘fibrin degradation products increased’ and ‘veno-occlusive liver disease.’ Conclusion Mining multiple databases enabled the identification of SOCs and AEs strongly associated with frequent adverse reactions to gemtuzumab ozogamicin and inotuzumab ozogamicin, offering valuable insights for clinical dosing guidance.

Adverse Event Reporting for Medications and Vaccines Before and During the COVID-19 Pandemic: An Observational and Retrospective Study

Objective: Compare the profile of suspected adverse events (AE) reports associated with medicines and vaccines before and during the COVID-19 pandemic. Method: An observational, retrospective study was conducted using data extracted from the VigiMed database. Spreadsheets were reviewed and processed, starting with the exclusion of the lines that had incomplete and uninterpretable data on the following variations related to the patient, related to the AE, related to the medication/vaccine and related to the notifier. Following database extract, reports were categorized into two groups: Group 1 (G1), before the pandemic; and Group 2 (G2), during the pandemic. Categorical variables were compared using absolute and relative frequency. Results: There was no difference between the notification profiles in the two groups about the sex and age of the individuals affected by AE related to medicines and vaccines. The notifiers in G1 were predominantly pharmacists (77.5%) while in G2, it was the consumers (55.9%). With respect to the products that were the target of the notifications, in G1 the most prevalent classes were analgesics, antibiotics and antineoplastics. In G2, there were vaccines against COVID-19 and immunosuppressants. About reports of suspected fatal AE related to medicines and vaccines, the most prevalent products in G1 were antimicrobials and antiepileptics, while G2 included antineoplastics, COVID-19 vaccines and immunosuppressants. Conclusion: The comparative of AE to drugs and vaccines notifications revealed that the COVID-19 pandemic contributed to a change in the profile of the notifiers, as well as in the type of product targeted by the notifications most frequently reported. These findings highlight the landscape of pharmacovigilance during public health emergencies.

Disproportionality Analysis of Ivabradine in the US FDA Adverse Event Reporting System: A Real-World Study Across Overall and Indication-Specific Populations.

Ivabradine, a selective If current inhibitor, is widely prescribed for heart failure and chronic angina; however, its post-marketing safety profile across diverse clinical contexts remains underexplored. This study analyzed ivabradine-associated adverse events (AEs) using the US Food and Drug Administration Adverse Event Reporting System, with a focus on overall patterns and indication-specific subgroups. We reviewed reports from the US Food and Drug Administration Adverse Event Reporting System from quarter 2, 2015, to quarter 2, 2024, and conducted a disproportionality analysis using four methods: reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. We stratified AEs by clinical indications (tachycardia, heart failure, coronary artery disease) and prioritized them using a semi-quantitative scoring system and important or designated medical event criteria as defined by the European Medicines Agency. A total of 2733 ivabradine-related AE reports were identified, involving 24 system organ classes. Cardiac disorders (n = 1045) and eye disorders (n = 352) were most frequent, with bradycardia, arrhythmias, and photopsia being the leading events. Subgroup analyses revealed distinct AE profiles: sinus tachycardia and supraventricular tachycardia in the tachycardia subgroup; blurred vision and angina in coronary artery disease; and severe AEs-such as dyspnea, prolonged QT interval, and ventricular fibrillation-primarily in heart failure. One rare but notable designated medical event, transient blindness (n = 3), was also identified. Ivabradine shows an overall favorable safety profile. Most AEs appear related to underlying disease or comedications rather than intrinsic drug toxicity. These findings support indication-specific monitoring to enhance clinical safety and pharmacovigilance.

Suicidality Risks Associated with Finasteride, a 5-Alpha Reductase Inhibitor: An Evaluation of Real-World Data from the FDA Adverse Event Reports

Background: Finasteride, a 5α-reductase inhibitor, is used for androgenetic alopecia and benign prostatic hyperplasia. However, concerns have emerged about its psychiatric side effects, including suicidality. This study analyzed finasteride-related reports from the FDA Adverse Event Reporting System (FAERS) to identify potential safety signals. Methods: Adverse events reported from 2015 to 2024 were extracted using preferred terms, quantified using Bayesian analysis and disproportionality metrics, including empirical Bayesian geometric mean (EBGM), information component (IC), reporting odds ratio (ROR), and proportional reporting ratio (PRR). Results: Most were male (87%), with 43% aged 18–40 years, primarily using finasteride for hair loss. Disproportionality metrics for suicidality-related events fluctuated between 2019 and 2024. In 2019, the ROR was 27.51 (95% CI: 23.22–32.58), the PRR was 21.96 (95% CI: 18.54–26.01), the EBGM was 20.50, and the IC was 4.36. A slight decline was observed in 2020, a surge in 2021, and a peak in 2022 (ROR 34.64 (95% CI: 28.36–41.88), PRR 27.82 (95% CI: 22.30–34.61), EBGM 24.96, IC 4.64). Although a sharp rise in suicidality reports was noted in 2024, the rates of ROR and PRR dropped to 19.04 (95% CI: 17.02–21.30) and 16.53 (95% CI: 14.78–18.50), respectively. Serious outcomes such as disability (18.7%), life-threatening events (12.9%), and death (7.5%) were also noted. Conclusions: The upward trend in suicidality-related safety signals among young male users since 2019, which peaked in 2024, reflects emerging safety concerns among finasteride users, reinforcing the need for pharmacovigilance. Collaborative action among healthcare professionals, regulatory authorities, and pharmaceutical companies, along with clear warnings and mental health assessments before and throughout finasteride therapy, can mitigate potential psychiatric risks and enhance patient safety.

Drug adverse events associated with temozolomide administration: A real-world pharmacovigilance study using the FAERS database from 2014 to 2024.

BackgroundTemozolomide, an alkylating agent with antitumor effects, is commonly used to treat newly diagnosed glioblastoma multiforme (GBM) and recurrent or progressive GBM or anaplastic astrocytoma. As its usage has increased, so have reports of associated adverse events (AEs), though these AEs have not been systematically documented. Pharmacovigilance plays a key role in assessing the benefits and risks of drugs.ObjectiveTo systematically identify AEs associated with temozolomide through analysis of data from the FDA Adverse Event Reporting System (FAERS) in real-world settings.ResultsA total of 11,400 reports identified temozolomide as the primary suspect drug, leading to the identification of 200 AE signals. These AEs were linked to 27 system organ classes (SOCs), with the top five being general disorders and administration site conditions (n = 5151, ROR = 1.18), injuries, poisonings, and procedural complications (n = 2825, ROR = 0.98), blood and lymphatic system disorders (n = 2375, ROR = 6.32), gastrointestinal disorders (n = 2254, ROR = 1.08), and nervous system disorders (n = 2084, ROR = 1.05). New suspected AEs, such as mutagenic effects, aspergillosis, and intracranial hemorrhage, were identified, which were not listed in the drug's package insert. The majority of AEs (n = 758) occurred within the first month of use, though some were reported up to a year after treatment (n = 126).ConclusionsThese findings provide valuable insights for optimizing temozolomide use and minimizing its potential side effects, enhancing its safety in clinical practice.

SGLT2 inhibitors may increase creatinine clearance: data mining utilizing the FDA Adverse Event Report System database and pharmacokinetic study with rats.

Augmented renal clearance is a condition in which creatinine clearance exceeds 130 ml/min/1.73 m². The present study aimed to identify drugs that increase creatinine clearance. We initially investigated drugs associated with an upsurge in the reporting frequencies of "creatinine renal clearance increased" (CRCI) and "glomerular filtration rate increased" (GFRI) using the FDA Adverse Event Reporting System (FAERS) database. Effect of the drugs on renal clearance of creatinine and lithium was examined using rats. The database contained 625 reports on CRCI and GFRI. Among the primary suspect drugs identified, empagliflozin had the highest number of reports (29), followed by canagliflozin (27), emtricitabine/tenofovir (21), and sacubitril/valsartan (21). Dapagliflozin had 16 reports. Reporting odds ratios (95% confidence intervals) for empagliflozin, canagliflozin, and dapagliflozin were 29.7 (20.5-43.1), 28.6 (19.5-42.1), and 19.7 (12.0-32.3), respectively. In rats infused with phlorizin, a typical inhibitor of sodium-glucose cotransporters (SGLTs), increases were observed in fractional glucose excretion, creatinine clearance, and the renal clearance of lithium. The plasma concentration of creatinine remained unchanged, while that of lithium decreased. Renal glucose excretion in rats administered phlorizin correlated with creatinine clearance (r = 0.859). These results suggest that SGLT2 inhibitors may increase renal clearance of creatinine or drugs.