Expert Opinion on Drug Safety最新文献

Background: Selinexor is approved for the treatment of relapsed or refractory multiple myeloma. However, a comprehensive understanding of adverse events associated with selinexor is lacking.

Methods: Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data of the US Food and Drug Administration Adverse Event Reporting System (FAERS). The disproportionality analysis was conducted. Four algorithms were employed to evaluate the signals of adverse events. The adverse effects of selinexor combined with dexamethasone were compared with bortezomib and dexamethasone. Sensitivity analysis was performed to exclude consumer-reported adverse events. The onset of adverse reactions were calculated.

Results: A total of 1,698 reports related with selinexor from FAERS were identified. 6 significant system organ class and 42 significant preferred terms (PTs) were found. Unexpected significant adverse events including mania, acute kidney injury, orthostatic hypotension, and embolisms were identified. 14 PTs reported significant signals in treatment of selinexor combined dexamethasone compared with traditional treatment of bortezomib and dexamethasone. 45.2% of adverse events occurred within the first month of starting selinexor.

Conclusions: Comprehensive analyses of selinexor related adverse events are helpful for clinical detection of adverse events and timely intervention, advancing selinexor's therapeutic progress in future treatment.

Objectives: This study aimed to describe the pulmonary toxicity of cyclin-dependent kinase 4/6 inhibitors (CDK 4/6 inhibitors) (palbociclib, ribociclib, and abemaciclib) in patients being treated for breast cancer using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Research design and methods: Disproportionality analysis was performed to assess pulmonary toxicity associated with CDK 4/6 inhibitors. Clinical characteristics, onset time, sensitivity analysis, subgroup analyses, drug combinations, comorbidities, and co-reported events were performed.

Results: Out of 83,505 CDK 4/6 inhibitor-related adverse events (AEs) documented in the FAERS database during the study period, 437 cases of pneumonitis, 555 cases of pulmonary edema, and 181 cases of pulmonary thrombosis related to CDK 4/6 inhibitors were analyzed. Pneumonitis and pulmonary thrombosis had the strongest signal strength in abemaciclib; pulmonary edema had the strongest signal strength in ribociclib. The median latency for pneumonitis, pulmonary edema, and pulmonary thrombosis was 66-173.5 days, 27-131 days, and 68-279 days, respectively. Pulmonary toxicity is statistically significant disproportionality in females as well as in patients over 60 years old.

Conclusion: Abemaciclib was most strongly associated with pneumonitis and pulmonary thrombosis. Ribociclib was most strongly associated with pulmonary edema. The correlation with pulmonary toxicity was, in descending order, abemaciclib, ribociclib, and palbociclib.

Objectives: Medroxyprogesterone acetate (MPA), a steroid progesterone, is widely used to treat endometriosis, menstrual disorders, and uterine bleeding in clinical practice. However, the safety profile of MPA requires comprehensive evaluation.

Methods: This study performed a retrospective analysis using real-world data extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Case reports from 2003 to 2023 were analyzed using methods like reporting advantage ratio (ROR), proportional report ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and empirical Bayes geometric mean (EBGM).

Results: In the case reports spanning from 2003 to 2023, showed 26,437 adverse events (AEs) related to MPA, mostly in females (25,639). Disproportionality analysis identified 116 ADRs across 19 system organ class (SOC) levels, including expected AEs like 'female breast cancer'(n = 8717) and 'ovarian cancer' (n = 459). Unexpected AEs, such as 'acquired diaphragmatic eventration'(n = 3), were also noted.

Conclusion: Our study identifies potential new and unexpected ADR signals linked to MPA, which align with clinical observations. Additional research is necessary to confirm these associations and address previously unrecognized safety concerns. This research provides a novel and distinctive approach to exploring drug-related AEs.

Background: This study aims to analyze adverse events (AEs) associated with naltrexone based on the FAERS database, providing a foundation for its safety monitoring.

Research design and methods: Disproportionality analysis methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) algorithms, were employed to quantify signals of naltrexone-related AEs.

Results: AEs related to naltrexone from the first quarter of 2013 to the fourth quarter of 2023 were extracted from the FAERS database for detailed analysis. Among a total of 41,757,311 reports 28,745 were directly associated with naltrexone, involving 27 organ systems. We identified 110 positive signals for AEs at the preferred term (PT) level using disproportionality analysis, which included known AEs such as agitation, depressed mood, sleep disorder, tremor, delirium, and decreased libido. Additionally, our findings suggested potential risks of restless legs syndrome, eosinophilic pneumonia, and otolithiasis, which were not mentioned in the drug's label, thereby supplementing the existing safety information.

Conclusions: The analysis of the FAERS database identified AEs associated with naltrexone, contributing to the awareness of clinical practitioners and pharmacists regarding the drug-related risk signals. This awareness facilitates timely preventive and therapeutic measures, ensuring patient safety.

Background: Drug-induced thrombocytopenia (DITP) often occurs in patients during clinical treatment. However, clinicians usually fail to distinguish which drugs can be plausible culprits accurately. We aimed to develop a large comprehensive drug benchmark database with DITP toxicity using the recommended method by FDA.

Research design and methods: We collected information from six databases that involved drug labeling information, literature, safety signal mining and laboratory testing to generate the annotated drug list with DITP toxicity. Then, we descripted the DITP positive-negative distribution based on the Anatomical Therapeutic Chemical (ATC) coding system; hotspot analysis was conducted to identify therapeutic categories of drugs within each organ system that warrant attention regarding DITP.

Results: The DITPst database comprised 1,765 drugs, of which 858 were DITP-positives, whereas 907 were negatives. The investigation of distribution across various therapeutic categories revealed the most frequent DITP-positive categories were immunostimulants (10/11), anti-inflammatory, and antirheumatic products (28/32), and antibacterials for systemic use (102/121). On the contrary, the least frequent DITP-positive therapeutic categories were diagnostic radiopharmaceuticals (12/12), pituitary and hypothalamic hormones and analogues (17/18), and drugs for constipation (16/17).

Conclusions: We consider the DITPst benchmark database to be an invaluable resource for the community to improve DITP safety research and drug development.

Background: Nasal septum perforation represents a significant clinical concern, with limited investigations into the role of medications in its etiology. This study utilizes the FDA Adverse Event Reporting System (FAERS) database to identify the drugs associated with nasal septum perforation and assess their risk.

Research design and methods: This retrospective pharmacovigilance study analyzed drug-induced nasal septum perforation data from January 2004 to December 2023. Disproportionality analysis using reporting odds ratio (ROR) assessed drug associations with nasal septum perforation.

Results: For 552 identified cases, the most commonly reported drugs were bevacizumab (n = 56), fluticasone propionate (n = 50), methotrexate (n = 34), hydrocodone and acetaminophen (n = 22), and paclitaxel (n = 17). Twenty-six drugs showed positive risk signals, with the top five being azelastine hydrochloride and fluticasone propionate (ROR = 173.82), beclomethasone dipropionate (ROR = 90.91), oxymetazoline (ROR = 53.77), desmopressin (ROR = 51.43), and leucovorin (ROR = 42.83). Intriguingly, 18 of these drugs did not list nasal septum perforation as a known side effect.

Conclusion: This study provides a comprehensive overview of drug-induced nasal septum perforation from a pharmacovigilance perspective, highlighting the need for further research to clarify these associations and update drug safety information to reduce patient risk.

Objective: The FDA Adverse Event Reporting System (FAERS) was used to evaluate the associations between oral anticoagulants (OACs) and acute kidney injury (AKI).

Methods: Disproportionality analysis was applied to data in the FAERS database from January 2004 to December 2023 to detect adverse events (AEs) for various OACs. The adjusted reporting odds ratios (RORs) calculated using multiple logistic regression were used to explore the risk factors for OACs-associated AKI.

Results: The crude RORs for the associations of AKI with warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban were 1.35, 2.14, 2.98, 1.33, and 3.56, respectively. The risk of OACs-associated AKI was affected by age and sex, being higher in those aged 65 years and males. The adjusted RORs for rivaroxaban, dabigatran, apixaban, and edoxaban were 1.26, 1.67, 0.65, and 2.06, respectively.Nearly 50% of AKI cases occurred within the first 2 months, and each OAC was of the early-failure type. Hospitalization and mortality rates for AKI patients after OACs were 45.53% and 22.98%, respectively.

Conclusions: The study revealed a strong association between AKI and OACs, emphasizing the need for regular renal function monitoring , especially in elderly male patients. Further in-depth research is needed to confirm these exploratory findings.

Background: Cardiovascular drugs can cross the placenta during pregnancy, potentially exposing the fetus to teratogenic effects. However, ethical constraints on clinical trials with pregnant women limit safety data and result in inadequate drug labeling.

Research design and methods: Using the FAERS database (2004-2023), we conducted a retrospective pharmacovigilance study analyzing adverse event reports involving congenital anomalies in newborns (<28 days). Signal detection methods included Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Our analysis concentrated on the systems or organs involved in the signals, particularly those with higher report counts or signal values, to explore the association between drugs and congenital abnormalities.

Results: Among 6,208 cases of congenital anomalies in newborns, 387 were linked to cardiovascular drugs, generating 97 signals for 16 drugs. Strong signals included sartans (renal failure, skeletal deformity), metoprolol (hypospadias, large-for-dates baby), amlodipine (gastrointestinal malformations), and statins, furosemide, and spironolactone (dysmorphism).

Conclusions: Enhanced monitoring is recommended for fetal malformations in women exposed to these drugs before or during pregnancy. While our findings suggest associations, they do not establish causality, highlighting the need for further research to ensure medication safety during pregnancy.

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Janus kinase (JAK) modulates cytokines involved in AD pathophysiology, and JAK inhibitors have emerged as effective pharmacotherapeutic remedies for AD. Abrocitinib, an oral selective inhibitor of JAK1, is indicated for the management of moderate-to-severe AD. The current study evaluated the adverse events (AEs) associated with abrocitinib in a real-world setting.

Methods: To quantify the signals of abrocitinib-associated AEs, we used the US Food and Drug Administration Adverse Event Reporting System (FAERS) for this pharmacovigilance study with two established pharmacovigilance methods.

Results: A total of 1071 AEs of abrocitinib were investigated as the primary suspected from the FAERS to detect and characterize relevant safety signals. The analysis revealed 85 signals for abrocitinib. The most common AE for abrocitinib was drug ineffective. The signal strength of eczema herpeticum was 515.87 (277.80-957.98) and 510.59 (5148.65) and exhibited the highest strength for abrocitinib. Rare AEs such as aggravated condition, pruritus, and hypersensitivity were not listed on the label, and attention to these AEs is required.

Conclusion: The analysis of the AE signals may provide support for clinical monitoring and risk identification of abrocitinib.

Introduction: The third-generation antiseizure medications used for the treatment of focal seizures, lacosamide, eslicarbazepine acetate, perampanel, brivaracetam, and cenobamate, may elicit serious adverse reactions which could be preventable if a prescriber is acquainted with the risk factors.

Areas covered: The literature search was conducted in MEDLINE, SCOPUS, and EBSCO databases, without time and language restrictions. Only clinical studies, observational human studies, case reports, and case series that reported serious adverse drug reactions and risk factors were considered.

Expert opinion: In order to prevent psychiatric side effects, the use of these drugs in patients with psychiatric disorders in the past should be avoided, or intensive monitoring of patients should be undertaken in order to detect psychosis or depression as early as possible. When prescribed eslicarbazepine and perampanel, serum sodium and ammonia levels should be periodically monitored. Lacosamide is associated with rhythm and conduction disturbances in the myocardium, so caution and ECG monitoring are required in people with cardiac diseases. Eslicarbazepine, cenobamate, and lacosamide can cause Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome and other allergic manifestations, so they should be used with caution in people with allergies in medical history.