Expert Opinion on Drug Safety最新文献

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently been linked to be associated with acute pancreatitis (AP), but the clinical characteristics are unclear. This study investigated the clinical characteristics of SGLT-2i and AP and provided reference for the prevention and treatment of AP.

Research design and methods: Case reports, case series, and clinical studies of SGLT2i induced AP were collected by retrieving Chinese and English data from the database until 31 December 2023.

Results: Twenty-one patients were included, with a median age of 50.5 years (range 26,73). SGLT-2i were mainly involved in empagliflozin (13 cases, 61.9%), canagliflozin (4 cases, 19%) and dapagliflozin (4 cases, 19%). The median time from initial administration to the onset of AP was 21 days (range 1, 120). Abdominal pain (21 cases, 100%) was the most commonly complained symptom. The median lipase value was 388 U/L (range 36, 10000), and the median amylase value was 535 U/L (range 26, 3765). Twenty-one patients recovered completely after stopping the drug and receiving conservative treatment.

Conclusions: SGLT-2i are associated with AP. Given the rising prescription of SGLT-2i, physicians should consider these agents as a potential cause of pancreatitis after excluding other etiologies.

Background: The comprehensive quantitative and comparative risk data of drug-induced erectile dysfunction (ED) are still lacking, and this study aims to supplement this information.

Research design and methods: We reviewed all the ED reports in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023 and summarized a potential ED culprit-drug list and its corresponding reporting frequency. The reporting odds ratio (ROR) method was used to conduct disproportionality analysis.

Results: A total of 20,098 ED reports were retrieved from the FAERS database, which recorded 734 different ED culprit-drugs, involving 74 drug classes. Finasteride was the drug with the highest reporting frequency, and urologicals was the drug class with the highest reporting frequency. In disproportionality analysis, 209 drugs with positive signals showed a close relationship with ED occurrence, among which finasteride was the drug with the highest signal strength. Among 209 drugs with positive signals, 27 were compound preparations, and the risk level of compound preparations was usually higher than their single active ingredient.

Conclusions: Our study integrated quantitative and comparative ED risk data of 734 drugs by using the FAERS database, which can provide reference information for regulators, medical personnel, and others involved in drug management and use.

Background: In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses.

Research design and methods: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis.

Results: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC₀₂₅ = 0.454 to IC₉₇₅ = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC₀₂₅ = 1.323 to IC₉₇₅ = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC₀₂₅ = 0.864 to IC₉₇₅ = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC₀₂₅ = 1.026 to IC₉₇₅ = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia.

Conclusion: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

Background: As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics were approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial.

Methods: The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis.

Results: Our study showed that thyroid gland disorders had the strongest signal in children. Patients aged 12-18 and treatment with minocycline are risk factors for thyroid adverse events (12-18: OR = 10.727 [7.113-16.177], p < 0.0001; minocycline: OR = 17.025 [10.475-27.678], p < 0.0001). Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia was primarily reported with tigecycline and eravacycline.

Conclusion: This study provided basic evidence for further research on tetracyclines-related adverse events. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.

Background: Vancomycin-induced acute kidney injury (VI-AKI) is one of its serious adverse reactions. The purpose of this study is to discuss the risk factors for VI-AKI in overweight patients and construct a clinical prediction model based on the results of the analysis.

Methods: Multivariable logistic regression analysis was used to identify risk factors for VI-AKI and constructed nomogram models. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA).

Result: Cancer (OR 4.186, 95% CI 1.473-11.896), vancomycin trough concentration >20.0 μg/mL (OR 6.251, 95% CI 2.275-17.180), concomitant furosemide (OR 2.722, 95% CI 1.071-6.919) and vasoactive agent (OR 2.824, 95% CI 1.086-7.340) were independent risk factors for VI-AKI. The AUC of the nomogram validation cohorts were 0.807 (95% CI 0.785-0.846). The calibration curve revealed that the predicted outcome was in agreement with the actual observations. Finally, the DCA curves showed that the nomogram had a good clinical applicability value.

Conclusion: There are four independent risk factors for the occurrence of VI-AKI in overweight patients, and the nomogram prediction model has good predictive ability, which can provide reference for clinical decision-making.

Background: Sugammadex is a novel agent that reverses neuromuscular blockade during general anesthesia. Recent case reports have raised concerns regarding potential cardiac adverse events (CAEs). However, no large-scale real-world studies have yet evaluated the potential link between sugammadex and CAEs.

Research design and methods: Data from the FDA Adverse Event Reporting System were obtained. The association between sugammadex and CAE was evaluated using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Serious outcomes resulting from sugammadex-related CAEs were assessed, and complications associated with CAEs were evaluated.

Results: Nineteen CAEs were identified and classified into two categories: cardiac arrhythmias and coronary artery disorders. The most frequent CAEs were bradycardia (n = 202), cardiac arrest (n = 119), tachycardia (n = 30), and Kounis syndrome (n = 22). Subgroup analysis based on age, sex, and weight revealed parallel findings. The CAEs most likely to result in serious consequences were pulseless electrical activity and cardiac arrest. The most common concurrent adverse effects with CAEs were hypotension (n = 51), anaphylactic reactions (n = 46), and anaphylactic shock (n = 23).

Conclusion: This study suggests a potential link between sugammadex and CAEs, highlighting the need for careful monitoring and personalized risk assessment, especially in patients with cardiovascular risk factors.

Background: Angiotensin receptor blockers (ARBs) are widely used for treating hypertension and heart failure. Angioedema has been reported as a controversial adverse effect of ARBs and the evidence on individual ARB risks is limited. This study aimed to assess signals of angioedema with different ARBs using the US FDA Adverse Event Reporting System (AERS) database.

Research design and methods: Reports of angioedema from 2004 to 2024 in AERS with an ARB as the primary suspect were extracted using Medical Dictionary for Regulatory Activities queries. Disproportionality analyses including reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker were conducted to identify safety signals for individual ARBs.

Results: A total of 3,683 unique reports met the selection criteria. Irbesartan and losartan generated signals in all statistical measures, followed by telmisartan and candesartan in some measures. Valsartan had the highest report count. Most reports reported hospitalization, prolonged hospitalization or life-threatening outcomes consequent to angioedema.

Conclusion: This pharmacovigilance study using AERS highlights potential higher risks of angioedema with losartan and irbesartan compared to other ARBs, warranting validation through prospective epidemiological studies to characterize individual ARB safety profiles.

Background: Previous studies have documented an increased risk of pulmonary embolism (PE) in patients with schizophrenia taking antipsychotics (APs). However, specific data from real-world studies remain limited. This study aims to investigate the potential relationship between APs and PE.

Research design and methods: In the Food and Drug Administration Adverse Event Reporting System (FAERS), from the first quarter of 2018 to the first quarter of 2023, all PE cases suspected of being induced by APs were collected for disproportionality analysis, and the reporting odds ratio (ROR) was used to evaluate associations. Mortality, life-threatening events, and hospitalizations were also analyzed for each APs.

Results: A total of 1,676 cases of PE related to APs were included. APs were significantly associated with PE (ROR 2.00, 1.91-2.10), including chlorpromazine (n = 41), haloperidol (n = 164), loxapine (n = 37), olanzapine (n = 461), paliperidone (n = 161), quetiapine (n = 526), risperidone (n = 274), aripiprazole (n = 254), and clozapine (n = 234). The median onset time of PE was 29 days. Among all cases, 347 (20.7%) resulted in death, with haloperidol (53.2%) having a higher mortality rate than other APs.

Conclusions: APs may increase the risk of PE in patients with schizophrenia.