Spontaneous Reports Research Articles

The Association Between Dextromethorphan/Bupropion with Alcohol and Substance Misuse: Reports to the Food and Drug Administration Adverse Event Reporting System (FAERS).

Dextromethorphan/bupropion (DXM/BUP) received Food and Drug Administration (FDA) approval for the treatment of adults with major depressive disorder (MDD) in August 2022. This combination is not known to have abuse liability and is not currently scheduled by the Drug Enforcement Administration (DEA). Notwithstanding, dextromethorphan is a drug of abuse. Herein, we sought to determine whether DXM/BUP has alcohol and/or substance misuse liability. We evaluated spontaneous reports of terms such as "alcohol problem, alcoholism, alcohol abuse, substance dependence, substance use disorder (SUD), substance abuse, drug dependence, drug use disorder and drug abuse" in the FDA Adverse Event Reporting System (FAERS). The FAERS is a spontaneous reporting database of adverse events submitted to the FDA. We performed a comparative assessment of the alcohol and/or substance misuse liability of DXM/BUP since its market authorization in August 2022, using acetaminophen as the control. Dextromethorphan served as the upper-bound reference point. Our findings showed that, since August 2022, dextromethorphan had a significant reporting odds ratio (ROR) for "drug abuse." In contrast, DXM/BUP did not have a significant ROR for any of the categories of alcohol and/or substance misuse evaluated. Limitations of our findings derive largely from the limitations of the FAERS and its data capture method. The absence of alcohol or substance misuse reported to the FAERS with DXM/BUP accords with the lack of evidence of abuse liability prior to FDA approval and its non-scheduling by the DEA.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®)

IntroductionReports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established. Research design and methodsThe analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0. ResultsWe searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For “depression/suicidal”, the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008). ConclusionUnlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data.

Integration of FAERS, DrugBank and SIDER Data for Machine Learning-based Detection of Adverse Drug Reactions

AbstractTraditionally, disproportionality analysis (DPA) methods are employed for signal detection in pharmacovigilance, but these methods utilize only a limited portion of the data available from spontaneous event reports (SERs). This research aims to enhance signal detection by applying machine learning (ML) methods that can leverage additional data. We create a dataset by integrating SER data from the FDA Adverse Event Reporting System (FAERS) with biological and chemical data from DrugBank, and information on known adverse drug reactions (ADRs) from Side Effect Resource (SIDER). The known ADRs from SIDER are used to label the dataset for ML training. Using the AutoML library TPOT, ML models are trained on this dataset. Our findings indicate that ML models, even when trained with the same features as DPA methods, achieve higher recall and precision. Moreover, incorporating additional features related to drugs and events significantly boosts the performance of ML models. Analysis using the explainable AI (XAI) technique SHAP reveals that the drug name, event name, and fifth-level ATC code are the most influential features for model predictions. These ML models offer a promising alternative or supplement to conventional DPA methods for signal detection in pharmacovigilance.

Adverse Event Profile of First-line Drugs for Treating Patent Ductus Arteriosus in Neonates: A Disproportionality Analysis Study of USFDA Adverse Event Reporting System.

Acetaminophen, ibuprofen, and indomethacin are widely used as first-line drugs for patent ductus arteriosus (PDA) closure in preterm neonates. However, their relative safety profiles remain unclear. Adverse event reports related to the first-line drugs used in PDA and neonates in general were retrieved from the US Food and Drug Authority (FDA) Adverse Event Reporting System. Deduplicated reports were analyzed using proportional reporting ratios and reporting odds ratios to identify disproportionality safety signals between drugs. A total of 969 unique reports related to the first-line drugs used in PDA and 499 reports in the neonatal period were included. Acetaminophen signals primarily involved the liver, while ibuprofen and indomethacin signals pertained to gastrointestinal, renal, vascular, and mortality outcomes. Higher occurrences of death were reported with indomethacin and ibuprofen compared with acetaminophen. This first comparison of PDA drug safety profiles from spontaneous reports highlights some differences, with acetaminophen potentially conferring a safer adverse effect profile overall. While limitations include missing data and reporting biases, the signals warrant further validation. Given its comparable efficacy to ibuprofen, as demonstrated in other studies, acetaminophen has the potential to be preferred as an initial medical therapy for PDA.

Medication Errors Associated with the Use of Levofloxacin: An Analysis of the National Database of Spontaneous Reports

Medication Errors Associated with the Use of Levofloxacin: An Analysis of the National Database of Spontaneous Reports

Suicidal behaviour and CFTR modulators: A case series and WHO database disproportionality analysis

BackgroundA highly effective therapy involving elexacaftor, tezacaftor, and ivacaftor (ETI) for cystic fibrosis (CF) patients has recently raised safety concerns regarding potential psychiatric disorders. The manuscript reports cases of suicide attempts in patients receiving ETI and investigates putative causality using the WHO spontaneous reporting database. MethodsFirst, four cases of suicide attempts/self-injury are described. Second, a disproportionality analysis was conducted using spontaneous reports collected in Vigibase through the standardised MedDRA Query (narrow version) "Suicide/Self-injury" and ETI exposure. Reporting Odds Ratio (ROR) was calculated for the main and subgroup (i/suicide attempt, ii/suicidal ideation) analyses. Sensitivity analyses were performed with variations in exposure, to ivacaftor/lumacaftor to assess the intrinsic psychiatric risk of CF patients, and paracetamol as a positive control for suicide attempt and a negative one for suicidal ideation. Exposure to reduced-dose ETI was studied to evaluate the dose-gradient effect. ResultsFour cases of suicide attempt/self-injury occurred 3 to 13 months after ETI initiation in CF patients and were reported to the Bordeaux Pharmacovigilance centre. Aside, in Vigibase, ETI is associated with an increased likelihood of reporting suicidal behaviour (ROR 2.5, 95 % CI[2.1; 2.8]). A signal of disproportionate reporting was found for the subgroup of suicide attempts (1.4, 95 % CI[1.2; 1.8]), unlike ivacaftor/lumacaftor, which was associated only with the risk of reporting suicidal ideation. Significant ROR values were also found for reduced-dose ETI for all psychiatric effects studied except suicide attempt. ConclusionsETI exposure is related with increased reporting of suicidal behaviour. A potential dose-dependent effect merits further investigation.

Influence of loop diuretics on denosumab-induced hypocalcaemia in osteoporosis: a retrospective observational analysis

BackgroundWe examined whether denosumab-induced hypocalcaemia is evident in osteoporosis when given loop diuretics that promote urinary calcium excretion.MethodsJapanese Spontaneous Adverse Drug Event Reports was analyzed to examine signals for denosumab-induced hypocalcaemia co-administered loop diuretics. We retrospectively included osteoporotic patients to detect predictors for denosumab-induced hypocalcaemia (corrected calcium level < 8.5 mg/dL) using multivariate logistic regression analysis. We compared differences in corrected calcium levels (ΔCa = nadir-baseline).ResultsA significant signal for hypocalcaemia was detected (Reporting odds ratio = 865.8, 95% confidence interval [95% CI]: 596.8 to 1255.9, p < 0.0001). Among 164 patients (hypocalcaemia, 12%), loop diuretics have a significant association with hypocalcaemia (odds ratio [OR] = 6.410, 95% CI: 1.005 to 40.90, p = 0.0494). However, hypocalcaemia was found to be lower in high corrected calcium levels at baseline (OR = 0.032, 95% CI: 0.005 to 0.209, p < 0.0001) and calcium and vitamin D supplementation (OR = 0.285, 95% CI: 0.094 to 0.868, p = 0.0270). In the non-hypocalcaemia, ΔCa decreased significantly in the denosumab plus loop diuretics than in the denosumab alone (-0.9 [-1.3 to -0.7] mg/dL vs. -0.5 [-0.8 to -0.3] mg/dL, p = 0.0156). However, ΔCa remained comparable in the hypocalcaemia despite loop diuretics co-administration (-1.0 [-1.2 to -0.8] mg/dL vs. -0.8 [-1.5 to -0.7] mg/dL, p = 0.7904).ConclusionsLoop diuretics may predispose to developing denosumab-induced hypocalcaemia.

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Safety and Efficacy of Mirtazapine Compared to Sertraline in Hemodialysis Patients with Major Depressive Disorder: A Randomized Controlled Clinical Trial

Background: This study aimed to compare the efficacy and tolerability of mirtazapine and sertraline in moderately depressed patients undergoing chronic hemodialysis therapy. Methods: In this double-blind clinical study, 54 hemodialysis patients diagnosed with moderate to severe depression, scoring greater than 18 on the Beck Depression Inventory, version II (BDI-II), were randomly assigned to receive 12 weeks of treatment with either mirtazapine (15mg/day) plus placebo or sertraline (50 mg/day) plus placebo. Efficacy outcomes were assessed by evaluating changes in baseline BDI-II scores, as well as rates of response and remission at weeks 2, 4, 8, and 12 of treatment. The impact of the antidepressant treatment on the patient’s health-related quality of life was also assessed at the end of the treatment phase, with ratings ranging from 0 (the worst impact) to 10 (the best impact). Safety and tolerability of the study medications were monitored using an antidepressant side effect checklist and through spontaneous participant reports. Both efficacy and tolerability analyses were conducted on the intent-to-treat sample. The p-values less than 0.01 based on Bonferroni's multiple-testing correction method were considered statistically significant. Results: The mixed models for repeated measures analysis revealed a significant time effect on depression symptoms (p &lt; 0.001), indicating improvement in both treatment groups over the study period. However, the treatment effect was not significant (p = 0.160), suggesting no overall difference in depressive symptoms between groups. The interaction between time and treatment was significant (p = 0.020), indicating varying changes in depressive symptoms over time between treatment groups. At week two, patients receiving mirtazapine had a lower mean BDI-II score than those receiving sertraline (15.62±5.24 versus 18.92±5.03), but the difference between the groups was not statistically significant (p-value = 0.022). Subsequent assessments at weeks 4, 8, and 12 showed comparable mean BDI-II scores between both treatment groups. Furthermore, at all assessment points, the rate of responders (≥50% reduction in BDI-II total score from baseline) and the rate of remitters (BDI-II total score of &lt;10) were similar between the treatment groups. However, mirtazapine- treated patients scored higher in assessing the overall impact of the treatment on their quality of life compared to the sertraline-treated group (7.40±1.18 versus 6.51±1.15 p-value = 0.007). Regarding safety and tolerability, although there were differences in the pattern of adverse effects between the treatment groups, the proportion of patients experiencing at least one adverse effect and the rate of dropouts were similar between the two groups, indicating comparable tolerability for both medications. Conclusion: Our results suggest that the efficacy and tolerability of mirtazapine are equivalent to those of sertraline in treating moderate depression in hemodialysis patients. However, mirtazapine appears to have a more favorable effect on patients' health-related quality of life compared to sertraline. Trial Registration: The trial was registered at the Iranian Registry of Clinical Trials (https://www. irct.ir/trial/66756, identifier code: IRCT20120215009014N445). Registration date: 2022-11-09.

ORENITRAM’s decadal journey: unveiling safety profiles and adverse event through a real-world pharmacovigilance study of FAERS events

ABSTRACT Background ORENITRAM, an oral treprostinil formulation, was approved in 2013 for pulmonary arterial hypertension (PAH) treatment, necessitating ongoing safety monitoring. Research design and methods This retrospective analysis used FDA Adverse Event Reporting System data from Q4 2013 to Q4 2023, employing disproportionality analysis and the reporting odds ratio (ROR) to identify adverse events (AEs) linked with ORENITRAM. Results Out of 15,660,695 reports, ORENITRAM was the primary suspect in 10,125 cases. We identified 174 significant adverse events across 27 organ systems, with notable issues like pulmonary edema, ascites, and ventricular fibrillation. Females reported more AEs (75.6%) than males (24.0%), suggesting potential metabolic differences. AEs were most common within 30 days of starting treatment or after one year. Conclusions The study indicates significant safety issues with ORENITRAM, including serious unexpected events such as pulmonary edema, ascites, and ventricular fibrillation. These findings highlight the necessity for careful clinical monitoring and effective risk management, particularly with observed gender differences in AE profiles. The study’s retrospective nature and reliance on spontaneous reports may affect result generalizability.

Safety profile of levonorgestrel intrauterine system: Analysis of spontaneous reports submitted to FAERS

The levonorgestrel-releasing intrauterine system (LNG-IUS) is an established, long-acting contraceptive option. With the widespread use of the LNG-IUS, drug-reported adverse events (AEs) have also garnered significant attention. In this study, we conducted a real-world analysis using the FDA's Adverse Event Reporting System (FAERS) database to assess the incidence of AEs associated with LNG-IUS use. Data from FAERS spanning from 2004Q1 to 2024Q1 were reviewed, with a focus on reports in which LNG-IUS was the primary suspected and secondary suspect drug. Signal detection was carried out utilizing Standardized MedDRA Queries (SMQ) and Preferred Terms (PT), with reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) employed to identify Signals of Disproportionate Reporting (SDR) for AEs. A positive SDR was defined when all three methods indicated significance. Analysis of 13 SMQs revealed notable SDRs in ear and eye disorders, cardiac arrhythmias, and lipodystrophy. Of the 61 suspected SDRs identified at the PT level, nearly half were not previously documented in labeling. Key potential signals of AEs associated with LNG-IUS use included increased heart rate, papilledema, idiopathic intracranial hypertension, cervical dysplasia, ruptured ovarian cyst, and uterine embedment and perforation. The findings underscore the importance of signal detection using FAERS data for identifying safety concerns related to LNG-IUS. Long-term observational studies are warranted to confirm and further elucidate these potential safety signals.

Ocular adverse events associated with platins: a disproportionality analysis of pharmacovigilance data and extensive systematic review of case reports

ABSTRACT Background Anti-cancer drugs, particularly platinum-based chemotherapy drugs, have been showing ocular adverse events (OAEs) in patients undergoing chemotherapy, which is concerning due to the potential impact on patient’s quality of life and the ability to continue effective cancer treatment. Research design and methods A retrospective case/non-case study was conducted using spontaneous reports on OAEs by platins from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and the Information Component (IC) to identify OAE signals for platinum-based chemotherapy drugs. In parallel, a review of case reports for OAEs from platins was conducted by a systematic literature search in PubMed and Google Scholar. Results Using disproportionality analysis, 69 signals were identified for platinum-based chemotherapy drugs and OAEs (carboplatin: 42, oxaliplatin: 16, cisplatin: 11). Choroidal infarction [PRR = 215.1; χ2 = 4527.1; lower bound (LB) ROR = 140.7; IC025 = 5.1] and orbital hemorrhage [PRR = 120.0; χ2 = 300.5; LB ROR = 35.1; IC025 = 1.3] were the strong signals identified for carboplatin. Optic disc hyperemia [PRR = 208.2; χ2 = 742.5; LB ROR = 74.1; IC025 = 2.2] and blindness cortical [PRR = 23.7; χ2 = 382.5; LB ROR = 14.8; IC025 = 3.1] were the signals identified for oxaliplatin and cisplatin, respectively. A total of 32 case reports of OAEs from platinum-based chemotherapy drugs were identified through a systematic search in PubMed and Google Scholar, strengthening the association. Conclusion The study revealed a potential risk of OAEs when using platinum-based chemotherapy drugs as an anticancer medication.

Safety assessment of brexanolone in the FAERS database: real adverse event analysis and discussion of side effects

ABSTRACT Background Postpartum depression (PPD) is linked to hormonal changes. Brexanolone, the first FDA-approved drug for PPD, is a potential treatment. This study analyzes Brexanolone’s safety using the FAERS database, highlighting its adverse effects and potential risk factors. Methods We analyzed FAERS data from Q3 2019 to Q3 2023, evaluating adverse reactions to Brexanolone. The analysis includes demographics, reporting regions, reporter identities, and types of adverse reactions. Results Most reports are from the United States, with consumers and physicians as primary reporters. Adverse reactions mainly involve severe systemic diseases, administration site reactions, injuries, intoxication, operational complications, and mental disorders. Specific adverse reactions include incorrect drug monitoring, PPD, intrusive thoughts, delayed treatment efficacy, sedation complications, product discontinuation, misuse, infusion site leakage and pain, and medication errors. Conclusion The study confirms known safety information about Brexanolone and provides comprehensive data for medical practices and public health decisions. However, relying on spontaneous reports may introduce biases and incomplete information. Continued monitoring and reporting of adverse reactions to newer drugs like Brexanolone remain crucial.

Adverse Event Profiles of the Third-Generation Aromatase Inhibitors: Analysis of Spontaneous Reports Submitted to FAERS.

The third-generation aromatase inhibitors (AIs), represented by letrozole, anastrozole, and exemestane, have been used as a standard first-line adjuvant therapy for postmenopausal breast cancer patients with positive hormone receptor. However, their safety in the real world has not been systematically analyzed. We used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate adverse event (AE) profiles of the three AIs, covering the period from Q1 2004 to Q3 2023. The time-to-event onset profiles and cumulative incidence were analyzed by Weibull shape parameter test and Kaplan-Meier method, respectively. The disproportionality analysis was utilized to assess drug toxicity risk. Based on the FAERS database, 18,035, 8242, and 7011 reports listing letrozole, anastrozole, and exemestane as primary suspected drugs were extracted, respectively. AEs associated with anastrozole displayed the latest onset (p < 0.0001); meanwhile, WSP test showed that all three AIs had early failure-type profiles. At the preferred term level, we acquired 95, 59, and 42 significant signals associated with letrozole, anastrozole, and exemestane, which involved 18, 13, and 15 system organ classes, respectively. The three AIs all reported that their strongest AE signal was trigger finger. Neutropenia was the most frequent AE for letrozole, while the highest occurrences of anastrozole and exemestane were arthralgia. We also found that interstitial lung disease, a rare but serious AE, showed strong signal intensity in all three AIs. Additionally, letrozole was also associated with lots of other rare but serious AEs in hematologic, respiratory, and hepatic systems, which were not recorded in the instructions. Our analysis of safety warning signals of the third-generation AIs from the FAERS database provided reference for clinical safe and rational drug use.

Cytokine release syndrome associated with immune checkpoint inhibitors: a pharmacovigilance study based on spontaneous reports in FAERS

ABSTRACT Objective To describe cytokine release syndrome (CRS) associated with immune checkpoint inhibitors (ICIs) reported in the FDA Adverse Event Reporting System (FAERS). Methods We obtained ICIs adverse event (AE) reports from January 2011 to September 2023 from the FAERS database. The preferred term (PT) ‘cytokine release syndrome’ from the Medical Dictionary for Regulatory Activities (MedDRA) 26.1 was used to identify cases with ICIs-related CRS. The reporting odds ratio (ROR) of the disproportionality method was performed to quantify the association between CRS and ICIs treatment strategy. Results Three hundred and ninety-five cases were gathered. 42.03% of the patients were aged 18 to 65. Male patients outnumbered female patients (53.67% vs. 34.94%). The prevalent potential cancer types were lung cancer (33.42%) and skin cancer (20.51%). Japanese were responsible for the majority of ICIs-related CRS cases (176 cases). The combination of nivolumab and ipilimumab resulted in the most CRS cases (138 cases), and the ICIs combination therapy had the highest ROR signal value (ROR = 11.95 [10.14–14.06]). ICIs-related CRS had a median time to onset of 14 days (interquartile range [IQR] 7–43.25). Conclusions ICIs-related CRS is an increasingly important immune-related AE. Our study provided helpful information to help medical professionals learn more about ICIs-related CRS.

Characteristics and trends in adverse drug reactions in Ghana-evidence of spontaneous reports, 2005-2021.

Adverse drug reaction (ADR) monitoring is crucial in ensuring patient and pharmaceutical safety. However, there is a lack of evidence regarding ADR reporting trend pattern in Ghana. This study, therefore, aimed to analyse and characterise trends in ADRs reported in Ghana over 16years. We retrospectively analysed individual case safety retorts (ICSRs) received by the Ghana National Pharmacovigilance Centre from 2005 to 2021. Jointpoint regression was used to estimate age-adjusted ADR rates, stratified by sex and patient characteristics, suspected medication groups, clinical indications, and the manifestation of ADRs. To evaluate trends over time, the percentage annualised estimator was used. We identified a total of 6853 ICSRs from 2005 to 2021. The age-adjusted ICSR rates increased significantly from 2005 to 2019, with an annual increase of 18.6%; however, there was a downward trend from 2019 to 2021, although not statistically significant. Males accounted for the majority (64.3%) of ICSRs compared to females (35.7%). The suspected medication group most frequently associated with ADRs were antiprotozoals accounting for 35.6% of all ICSRs, while vascular disorders (21.0%) were the most commonly observed clinical indication in relation to ADRs. An increase in ICSR rates was noted for gastrointestinal disorders with an annual increase of 32.5% (95% CI, 20.6-45.6%; p < 0.001). Amodiaquine was the most commonly suspected medication (8.9%) associated with ADRs, while pruritus (7.2%) was the most frequently reported preferred term. The study provides a detailed overview of ICSRs received by the Ghana National Pharmacovigilance Centre over the past 16years and demonstrates an increasing trend of ADR-related medication use as well as clinical indications over time. The findings of this study call for multifaceted strategies aimed at reducing the risks associated with inappropriate drug use, and enhancing knowledge of medication safety, thus improving healthcare service delivery and patient safety.

Analysis of spontaneous reports of adverse drug reactions in children of different ages

Analysis of spontaneous reports of adverse drug reactions in children of different ages

The Association Between Deep Vein Thrombosis, Pulmonary Embolism, and Janus Kinase Inhibitors: Reporting Status and Signal Detection in the Japanese Adverse Drug Event Report Database.

Although Janus kinase (JAK) inhibitors have expanding indications, deep vein thrombosis (DVT) and pulmonary embolism (PE) are serious adverse events associated with their use. Moreover, their analysis using the Japanese database of spontaneous adverse drug reaction reports has not yet been conducted. The objective of this study was to analyze the Japanese Adverse Drug Event Report database (JADER) to evaluate the association between JAK inhibitors and DVT and PE. JADER reports from April 2004 to October 2023 were analyzed. A classification of reports for the period covered was performed by drug, and an imbalance analysis was performed with oral JAK inhibitors as the target drug and DVT, PE, and "embolic and thrombotic events, venous" (Standardised MedDRA Query; SMQ) as the target adverse events. Reported odds ratios (ROR) and information components (IC) were calculated for signal detection. Overall, 6631 JAK inhibitor-related adverse events were reported, including 60 and 41 cases of DVT and PE, respectively. The ROR and IC of the JAK inhibitors for DVT were 2.52 (1.95-3.25) and 1.27 (0.41-2.13), while those of baricitinib for DVT were 4.37 (2.83-6.73) and 1.90 (0.47-3.33), respectively. ROR signals were detected for JAK inhibitors for PE and "embolic and thrombotic events, venous (SMQ)," overall and for several JAK inhibitors but none for IC. Several JAK inhibitors are under postmarketing phase vigilance, and the number of reported adverse events is low. However, when administering these drugs, care should be taken to avoid the development of thromboembolism, considering the patient's background.

Detection of muscular system adverse reaction signals in sacubitril/valsartan treatment combined with statins.

To detect muscular system adverse reaction signals of sacubitril/valsartan treatment combined with statins (atorvastatin, rosuvastatin, simvastatin) to provide a reference for clinical administration. Multiplicative and additive models were used to mine the FDA's spontaneous reports database to detect signals of drug-drug interactions between sacubitril/valsartan and statins. SAS 9.4 software was used to conduct statistical tests for suspicious signals to determine whether the signals were statistically significant. A total of 8,883,870 adverse reaction reports were analyzed. The combinations "sacubitril/valsartan - simvastatin - musculoskeletal muscle pain" had statistically significant correlation signals in both models (P < 0.05). The combination "sacubitril/valsartan - atorvastatin - myopathy" and "sacubitril/valsartan-simvastatin - myopathy" had statistically significant correlation signal in the multiplicative model (P < 0.05). Compared with a single drug, coadministration of sacubitril/valsartan with atorvastatin may increase safety risks to myopathy, with simvastatin may increase safety risks to the musculoskeletal pain and myopathy, which should be closely monitored in clinical practice.

Sex/gender differences in spontaneous reports to a French Addictovigilance centre.

To specify psychoactive substances and related complications observed in spontaneous reports (SRs) in women versus men, we assessed SRs on substance-linked acute toxicity sent to a French Addictovigilance centre. Over the period 2021-2022, 880 SRs were analysed (33.4% concerned women). Severe complications concerned more men than women (70.3% versus 59.5%; p = 0.0014). In women, the main implicated substances were psychoactive medications (opioids, benzodiazepines). The most frequently reported complication was suicidal behaviour (14.6% versus 7.8%, p = 0.002). In men, SRs concerned mainly illicit substances (cocaine, amphetamines) or misuse of opioid maintenance therapy or nitrous oxide. The main complications in men were infections (12.97% versus 5.4%, p = 0.0006) and neurological troubles (37.6% versus 23.5%, p < 0.0001).Our data highlight sex/gender disparities in substance use and complications, in agreement with recent literature and French national Addictovigilance data.