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Frontiers in Pharmacology 2024Triazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased....
INTRODUCTION
Triazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System.
METHODS
Data were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR).
RESULTS
Among 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively.
CONCLUSION
Isavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs.
PubMed: 38584605
DOI: 10.3389/fphar.2024.1255918 -
Expert Opinion on Drug Safety Apr 2024Dupilumab is a safe and effective biological drug that revolutionized the treatment of atopic dermatitis (AD). Concerning adverse events (AEs), the most commonly... (Review)
Review
INTRODUCTION
Dupilumab is a safe and effective biological drug that revolutionized the treatment of atopic dermatitis (AD). Concerning adverse events (AEs), the most commonly reported included ocular involvement, nasopharyngitis, and injection site reactions in clinical trials. Anyway, its use in daily practice is revealing novel dupilumab-induced manifestations.
AREAS COVERED
Relevant English literature (real-life studies, case series, reviews, and meta-analyses) regarding real-life adverse events induced by dupilumab were searched for up to 10 June 2023.
EXPERT OPINION
Dupilumab is an effective treatment for AD, showing favorable safety profile since no routine laboratory monitoring is recommended. However, several cutaneous and extracutaneous AEs have been reported in real-life setting expanding the pool emerged from clinical trials. In detail, dupilumab may determine de-novo onset or exacerbation of preexisting conditions, whose pathogenesis is still unclear and seems to involve Th1/Th2 and Th2/Th17 immune-response imbalance. Also, the heterogeneity and the variable onset time of AEs with respect to dupilumab initiation warrant a thorough patients' history collection and strict short- and long-term monitoring. Finally, the most appropriate management of patients with AEs related to dupilumab should take into consideration efficacy for AD as well as severity and nature of the AE, available treatment and patients' preferences.
Topics: Humans; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Administration, Cutaneous; Injections, Subcutaneous; Treatment Outcome; Severity of Illness Index
PubMed: 38470213
DOI: 10.1080/14740338.2024.2326480 -
Nutrients Feb 2024Red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins, mainly monacolin K) that act by inhibiting the activity... (Review)
Review
The Impact of Red Yeast Rice Extract Use on the Occurrence of Muscle Symptoms and Liver Dysfunction: An Update from the Adverse Event Reporting Systems and Available Meta-Analyses.
Red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins, mainly monacolin K) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The European Food Safety Authority (EFSA) assessed the use of RYR and, while pointing out several uncertainties regarding the available data, raised a warning related to the safety of RYR when used as a food supplement at a dose of monacolin as low as 3 mg/day. In their decision in June 2023, EFSA approved the use of monacolins from RYR at doses less than 3 mg/day. We therefore decided to interrogate the different adverse event reporting systems (FAERS and CAERS) and analyse the characteristics of the cases reported to be associated with RYR supplements, and we reviewed the most recent meta-analyses with a focus on the occurrence of muscle symptoms and liver dysfunction. In terms of all musculoskeletal disorders from September 2013 (when the first case related to RYR consumption was recorded) to 30 September 2023, 363,879 cases were reported in the FAERS, with the number of cases related to RYR consumption being very small and accounting for 0.008% of cases. In the same time frame, 27,032 cases of hepatobiliary disorders were reported, and the cases attributable to RYR ingestion accounted for 0.01% of all cases. A low rate of muscle symptoms and liver dysfunction attributed to RYR ingestion was also observed in the CAERS database, where only 34 cases of adverse muscle events and 10 cases of adverse liver events reported RYR as the suspect product, while 19 cases of both muscle events and 10 cases of adverse liver events reported it as a concomitant product. This profile mirrors that of meta-analyses of randomised clinical trials of RYR, in which RYR use was not associated with either liver dysfunction or muscular adverse symptoms.
Topics: Humans; Lovastatin; Dietary Supplements; Biological Products; Muscles; Liver Diseases; Plant Extracts
PubMed: 38337728
DOI: 10.3390/nu16030444 -
Sexual Medicine Oct 2023Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs).
Safety profile and signal detection of phosphodiesterase type 5 inhibitors for erectile dysfunction: a Food and Drug Administration Adverse Event Reporting System analysis.
BACKGROUND
Phosphodiesterase type 5 inhibitors (PDE5Is) are generally well tolerated but have been associated with uncommon and significant adverse events (AEs).
AIM
This study aims to investigate and compare the characteristics of AEs associated with PDE5Is used for erectile dysfunction and identify any safety signals in a postmarketing surveillance database between 2010 and 2021.
METHODS
A descriptive analysis was conducted for all AEs reported to the Food and Drug Administration Adverse Event Reporting System for 4 PDE5Is-avanafil, sildenafil, tadalafil, and vardenafil-indicated for erectile dysfunction between January 2010 and December 2021. The frequency of the most reported AEs and outcomes were identified. A disproportionality analysis based on proportional reporting ratio (PRR) and reporting odds ratio (ROR) was conducted for the most common and clinically important AEs to identify signals to gain insights into potential differences in safety profiles.
OUTCOMES
The outcome measures of the study are frequency of reported AEs and outcomes following AE.
RESULTS
A total of 29 236 AEs were reported for PDE5Is during the study period. The most reported AE was "drug ineffective" with 7115 reports (24.3%). Eight safety signals were detected across the 4 drugs. Key signals were sexual disorders (PRR, 3.13 [95% CI, 2.69-3.65]; ROR, 3.24 [95% CI, 2.77-3.79]) and death (PRR, 3.17 [2.5-4.01]; ROR, 3.211 [2.52-4.06]) for sildenafil, priapism (PRR, 3.63 [2.11-6.24]; ROR, 3.64 [2.12-6.26]) for tadalafil, and drug administration error (PRR, 2.54 [1.84-3.52]; ROR, 2.6 [1.86-3.63]) for vardenafil. The most reported outcomes were other serious events with 6685 events (67.2%) and hospitalization with 1939 events (19.5%).
CLINICAL IMPLICATIONS
The commonly reported AEs and detected signals may guide clinicians in treatment decision making for men with erectile dysfunction.
STRENGTHS AND LIMITATIONS
This is the first comprehensive report and disproportionality analysis on all types of AEs associated with PDE5Is used for erectile dysfunction in the United States. The findings should be interpreted cautiously due to limitations in the Adverse Event Reporting System, which includes self-reports, duplicate and incomplete reports, and biases in reporting and selection. Therefore, establishing a causal relationship between the reported AEs and the use of PDE5Is is uncertain, and the data may be confounded by other medications and indications.
CONCLUSION
PDE5Is demonstrate significantly increased risks of reporting certain clinically important AEs. While these events are not common, it is imperative to continually monitor PDE5I use at the levels of primary care to national surveillance to ensure safe utilization.
PubMed: 38034088
DOI: 10.1093/sexmed/qfad059 -
JAMA Mar 2024
Topics: Adverse Drug Reaction Reporting Systems; Communication; United States; Vaccines
PubMed: 38407864
DOI: 10.1001/jama.2024.1757 -
Asian Journal of Psychiatry Dec 2023Epidiolex, the first FDA-approved drug with cannabis extract, treats Dravet and Lennox-Gastaut syndromes. Using data from the FAERS database between 2018 and 2023, this...
Epidiolex, the first FDA-approved drug with cannabis extract, treats Dravet and Lennox-Gastaut syndromes. Using data from the FAERS database between 2018 and 2023, this study analyzed 13,275 Epidiolex-related adverse events. Through computational methods (ROR, PRR, BCPNN, EBGM), we found that real-world adverse reactions largely align with those in Epidiolex's drug leaflet. However, Seizure cluster, Blood ketone body decrease, Cortical visual impairment, Hyperactive pharyngeal reflex, and Poverty of speech emerged as potential new side effects not previously listed, warranting further attention for drug safety.
Topics: United States; Humans; Cannabidiol; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; United States Food and Drug Administration; Software
PubMed: 37949044
DOI: 10.1016/j.ajp.2023.103828 -
Heliyon Mar 2024Alpelisib was approved for treatment of breast cancer. We assessed the safety signals associated with alpelisib by data mining the FDA pharmacovigilance database.
BACKGROUND
Alpelisib was approved for treatment of breast cancer. We assessed the safety signals associated with alpelisib by data mining the FDA pharmacovigilance database.
METHODS
Data from the second quarter of 2019 to the fourth quarter of 2022 had been retrieved from the FAERS database. Disproportionality analysis by reporting odds ratio were used to evaluate the potential association between adverse events (AEs) and alpelisib.
RESULTS
A total of 5,980,090 reports were extracted, 18,149 of them were chosen with alpelisib as the suspected drug. After combining the same PRIMARYID, 5647 patients remained. We observed 10 system organ classes (SOCs) with a reported number >50 and associated with alpelisib as gastrointestinal disorders, general disorders and administration site conditions, metabolism and nutrition disorders, skin and subcutaneous tissue disorders, investigations and neoplasms benign, malignant and unspecified (incl cysts and polyps), immune system disorders, nervous system disorders, psychiatric disorders, eye disorders. The median time to AEs in these patients was 13 days, with an IQR (Interquartile Range) of 7-70 days. 61.12% AEs happened within the initial month of alpelisib usage.
CONCLUSION
Our study provided a more in-depth and extensive understanding of AEs that may be associated with alpelisib, which will help to reduce the risk of AEs in the clinical treatment of alpelisib. AEs with novel preferred term (PTs) were constipation, dysphagia, diabetic ketoacidosis, feeding disorder, urticaria, eye disorders and vision blurred. 61.12% of cases developed AEs within 30 days after taking alpelisib.
PubMed: 38510044
DOI: 10.1016/j.heliyon.2024.e27599 -
Expert Review of Vaccines 2024The rapid development of COVID-19 vaccines has provided crucial tools for pandemic control, but the occurrence of vaccine-related adverse events (AEs) underscores the...
INTRODUCTION
The rapid development of COVID-19 vaccines has provided crucial tools for pandemic control, but the occurrence of vaccine-related adverse events (AEs) underscores the need for comprehensive monitoring.
METHODS
This study analyzed the Vaccine Adverse Event Reporting System (VAERS) data from 2020-2022 using statistical methods such as zero-truncated Poisson regression and logistic regression to assess associations with age, gender groups, and vaccine manufacturers.
RESULTS
Logistic regression identified 26 System Organ Classes (SOCs) significantly associated with age and gender. Females displayed especially higher odds in SOC 19 (Pregnancy, puerperium and perinatal conditions), while males had higher odds in SOC 25 (Surgical and medical procedures). Older adults (>65) were more prone to symptoms like Cardiac disorders, whereas those aged 18-65 showed susceptibility to AEs like Skin and subcutaneous tissue disorders. Moderna and Pfizer vaccines induced fewer SOC symptoms compared to Janssen and Novavax. The zero-truncated Poisson regression model estimated an average of 4.243 symptoms per individual.
CONCLUSION
These findings offer vital insights into vaccine safety, guiding evidence-based vaccination strategies and monitoring programs for precise and effective outcomes.
Topics: Aged; Female; Humans; Male; Pregnancy; Adverse Drug Reaction Reporting Systems; COVID-19; COVID-19 Vaccines; United States; Vaccination; Vaccines
PubMed: 38063069
DOI: 10.1080/14760584.2023.2292203 -
Drug Discovery Today Sep 2023Adverse drug events (ADEs) are responsible for a significant number of hospital admissions and fatalities. Machine learning models have been developed to assess the... (Review)
Review
Adverse drug events (ADEs) are responsible for a significant number of hospital admissions and fatalities. Machine learning models have been developed to assess the individual patient risk of having an ADE. In this article, we have reviewed studies addressing the prediction of ADEs in observational health data with machine learning. The field of individualised ADE prediction is rapidly emerging through the increasing availability of additional data modalities (e.g., genetic data, screening data, wearables data) and advanced deep learning models such as transformers. Consequently, personalised adverse drug event predictions are becoming more feasible and tangible.
Topics: Humans; Drug-Related Side Effects and Adverse Reactions; Machine Learning
PubMed: 37467879
DOI: 10.1016/j.drudis.2023.103715 -
American Journal of Clinical Dermatology Mar 2024Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and...
BACKGROUND
Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and nonsegmental vitiligo. A postmarketing study with oral tofacitinib, approved for rheumatoid arthritis, triggered class warnings for JAK inhibitors, including risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. Because ruxolitinib cream is indicated for inflammatory conditions, it is subject to the same warnings as oral JAK inhibitors in the US. Here, nearly 14,000 patient-years of postmarketing safety data from the first year following market approval of ruxolitinib cream were reviewed.
METHODS
The Incyte global safety database (21 September 2021-20 September 2022) and US FDA Adverse Event Reporting System (as of 30 September 2022) were queried for adverse event (AE) reports received for ruxolitinib cream.
RESULTS
The search identified 294 postmarketing individual case safety reports containing 589 events, including four serious AEs and no fatal AEs. AEs (i.e., any unfavorable sign, symptom, or disease) representing >2% of all events included application site pain (n = 16), atopic dermatitis (n = 15), skin irritation (n = 15), scratch (n = 14), and condition aggravated (n = 13). The four serious AEs were skin cancer (n = 2), pericarditis, and thrombocytopenia (both n = 1), none of which had sufficient information to assess possible relatedness to ruxolitinib cream. Serious AEs associated with the class warnings for JAK inhibitors were not reported.
CONCLUSIONS
Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.
Topics: Humans; United States; Dermatitis, Atopic; Janus Kinase Inhibitors; Nitriles; Emollients; Pyrazoles; Pyrimidines
PubMed: 38243107
DOI: 10.1007/s40257-023-00840-1