Abstract / Summary
Abstract Background Intravenous iron isomaltoside is a third-generation iron replacement widely used for perioperative gynaecological iron deficiency anaemia (IDA). Multiple international reports have documented hypersensitivity reactions (HSRs) following infusion, yet large-scale real-world data focusing on Chinese gynaecological cohorts remain absent. This study aimed to characterise the clinical phenotypes and identify independent risk predictors of iron isomaltoside-associated HSRs to guide safer clinical administration. Methods A single-centre retrospective nested case–control pharmacovigilance analysis was performed using data extracted from the China Hospital Pharmacovigilance System (CHPS). All gynaecological inpatients receiving iron isomaltoside between July 2024 and December 2025 were screened. Confirmed HSRs were defined as cases with Naranjo causality score ≥ 5; each HSR case was 1:4 matched to control patients by primary gynaecological diagnosis, age (±5 years), and BMI (≤3 kg/m²). Multivariate logistic regression was applied to screen independent risk factors. Results A total of 611 patients with 627 iron isomaltoside infusion episodes were enrolled, with 27 confirmed HSR cases identified (overall incidence 4.42%; CHPS alert positive rate 13.99%). All hypersensitivity events occurred during infusion, with a mean onset time of 25.33 ± 30.92 min, and 74.07% arose within the first 30 min. Cutaneous/mucosal and respiratory manifestations predominated, and all patients achieved full resolution after symptomatic intervention. Multivariate regression revealed three independent risk factors: concomitant intravenous antibiotic use (OR=4.38, 95%CI 1.44–13.36), elevated baseline platelet count (OR=1.01, 95%CI 1.01–1.01), and reduced pre-infusion haemoglobin concentration (OR=0.94, 95%CI 0.91–0.98). Conclusions Iron isomaltoside-related HSRs predominantly develop within the initial 30 min of infusion in gynaecological IDA patients. Clinicians should implement intensified real-time monitoring for individuals receiving concurrent antibiotics, low baseline haemoglobin, or reactive thrombocytosis to minimise hypersensitivity risk. The CHPS platform enables efficient, large-scale real-time post-marketing drug safety surveillance for intravenous iron agents.