Paediatric drugsJournal Article
18 Jan 2025
This study aimed to provide a comprehensive review of adverse events (AEs) associated with factor Xa (FXa) inhibitors in pediatric patients.
We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and the European Union Clinical Trials Register for English-language records from the establishment of the database up to October 17, 2023. Both randomized controlled trials and single-arm trials were included. AEs were analyzed using a Bayesian hierarchical model. For the pharmacovigilance study, data from the US Food and Drug Administration Adverse Event Reporting System from January 1, 2007, to December 31, 2023, were obtained. The proportional imbalance method and the Medicines and Healthcare products Regulatory Agency method were used to detect AE signals. Further characterization of patients presenting with AEs was performed.
Of 451 records identified, 12 eligible studies were included. A total of 50.6% (95% Bayesian credible interval [CrI] 33.1-67.2, τ = 0.796) of patients experienced at least one AE, and 9.9% (95% CrI 3.9-19.5, τ = 0.552) developed at least one serious AE. Major and clinically relevant non-major bleeding occurred in 2.4% (95% CrI 0.8-4.8, τ = 1.61) of patients. The most common bleeding AEs were epistaxis (8.4% [95% CrI 3.9-14.9, τ = 1.96]), subcutaneous hematoma (6.4% [95% CrI 0.5-26.2, τ = 0.54]), and wound hemorrhage (3.7% [95% CrI 0.4-13.3, τ = 0.55]). Non-hemorrhagic AEs were pyrexia (9.2% [95% CrI 4.6-15.3, τ = 1.18]), vomiting (7.8% [95% CrI 4.0-12.3, τ = 0.08]), and abdominal pain (7.4% [95% CrI 1.5-19.4, τ = 0.84]). A total of 39 AE signals were detected in the pharmacovigilance study. The top three highest overall relative odds ratio (ROR) for AEs were observed for haemorrhoidal hemorrhage at 1211.82 (95% CI, 312.69-4696.29), thrombophlebitis at 134.64 (95% CI, 42.18-429.81), and deep vein thrombosis at 68.3 (95% CI, 42.53-109.68). Patients experiencing bleeding AEs had received a mean dosage of rivaroxaban 0.16 mg/kg and apixaban 0.08 mg/kg.
Systematically quantified AEs of FXa inhibitors in clinical trials and real-world studies provide an important guide for clinicians. The use of FXa inhibitors in pediatric patients is associated with an acceptable rate of AEs. The most common bleeding AE was epistaxis. Pediatric patients treated with FXa inhibitors were more prone to hemorrhoidal hemorrhage. A safe approach may involve prior use of other anticoagulants followed by careful administration of FXa inhibitors, with a dosing regimen tailored to age and weight. Close monitoring is recommended for peri-procedural anticoagulation and vomiting.
Declarations. Conflict of Interest: There are no financial conflicts of interest to disclose. Funding: This study was funded by the National High Level Hospital Clinical Research Funding (Multi-center Clinical Research Project of Peking University First Hospital, 2022CR67; Youth Clinical Research Project of Peking University First Hospital, 2023YC04); the National Natural Science Foundation of China (82073935 and 82274024).The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results Ethics Approval and Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Materials: The datasets are freely and publicly available on the website of US Food and Drug Administration ( https://www.fda.gov/ ) and ClinicalTrials.gov ( https://classic.clinicaltrials.gov/ ). Authors' Contributions: Data collection; SC, LS, MQH. Investigation: SC, LS, and GYM. Writing – original draft: SC, LS, and MQH. Writing – review and editing: GYM, QX, and YMC. Conceptualization, supervision, and funding acquisition: QX and YMC. All authors have read and agreed to the published version of the manuscript.
More resources:
Share: