Parenteral iron overdose: a scoping review.

Abstract

Introduction: Parenteral iron formulations are increasingly used worldwide for the treatment of iron deficiency anemia, yet clinical guidance for managing parenteral iron overdose is limited. Existing risk assessment and management frameworks, including the widely cited serum iron concentration threshold of 500 µg/dL, are derived primarily from oral iron poisoning and may not be directly applicable to parenteral exposures. This scoping review aims to map the existing literature on parenteral iron overdose, summarize exposure patterns, clinical presentations, laboratory findings, therapeutic interventions, and outcomes, and identify knowledge gaps to inform future clinical practice and research.

Methods: A scoping review was conducted following the Arksey and O'Malley framework and reported in accordance with the PRISMA extension for scoping reviews. Embase, Ovid MEDLINE, and Cochrane CENTRAL were searched through 31 December 2025, supplemented by Google Scholar and citation searching. Eligible studies described human reports of parenteral iron overdose or supratherapeutic repeated administration with sufficient original clinical detail. Two reviewers independently screened studies and extracted data, with disagreements resolved by a third reviewer. Findings were synthesized descriptively, and recurring patterns were identified through thematic analysis.

Results: Seventeen reports comprising 49 patients, published between 1995 and 2025, met the inclusion criteria. Most reports were single-patient case reports (14/17, 82.4%), and nearly half were conference abstracts (8/17, 47.1%), reflecting an evidence base composed predominantly of low-volume, case-level data. Exposures clustered into acute single-dose overdose (12/29 classifiable cases, 41.4%) and subacute cumulative overexposure (17/29, 58.6%). Iron sucrose and iron dextran predominated among acute reports, whereas ferric hydroxide polymaltose complex predominated among subacute cases (76.5%). Serum iron concentration did not consistently correspond to clinical severity: several cases with concentrations between 825 and greater than 2,000 µg/dL remained asymptomatic, whereas one case with a concentration of approximately 112 µg/dL developed shock, disseminated intravascular coagulation, and multiorgan failure. Liver toxicity was reported mainly in subacute cumulative cases (82.4%) but in none of the acute cases. Chelation practice varied widely: four acute overdose patients recovered without chelation despite serum iron concentrations of 1,301-1,830 µg/dL, whereas asymptomatic patients in other reports received prolonged chelation. Overall, 48 of the 49 included patients survived.

Discussion: The findings converge on three recurring themes. Parenteral iron overdose appears to represent a heterogeneous clinical syndrome distinct from classic oral iron poisoning, with phenotypes ranging from asymptomatic hyperferremia to infusion reaction-like presentations and subacute hepatic iron-loading syndromes. Conventional laboratory markers, particularly serum iron concentration, may not reliably reflect toxicologically active iron after parenteral exposure, likely reflecting biphasic kinetics, formulation-dependent iron release, and analytical interference from carbohydrate-bound iron. Chelation decisions may be better informed by clinical trajectory and exposure phenotype than by serum iron concentration alone.

Conclusion: Parenteral iron overdose appears to differ from oral iron poisoning in pathophysiology, laboratory behavior, and management considerations. Oral iron thresholds may not be directly applicable, and management may be better guided by clinical trajectory than by laboratory values alone. Given the limited quantity and heterogeneous quality of existing evidence, these observations should be interpreted as hypothesis-generating. Standardized reporting of parenteral iron overdose and multicenter pharmacovigilance collaborations are needed to clarify the true incidence and severity spectrum of this underrecognized medication safety issue.