The safety of intravenous iron preparations: systematic review and meta-analysis

Mayo Clin Proc. 2015 Jan;90(1):12-23. doi: 10.1016/j.mayocp.2014.10.007. Epub 2014 Oct 30.


Objective: To amass all available evidence regarding the safety of intravenous (IV) iron preparations to provide a true balance of efficacy and safety.

Methods: Systematic review and meta-analysis of all randomized clinical trials comparing IV iron to another comparator. All electronic databases until January 1, 2014, were reviewed. Primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included all-cause mortality and other adverse events (AEs). Subgroup analysis was performed on the basis of type of IV iron, comparator, treated condition, and system involved.

Results: A total of 103 trials published between 1965 through 2013 were included. A total of 10,390 patients were treated with IV iron compared with 4044 patients treated with oral iron, 1329 with no iron, 3335 with placebo, and 155 with intramuscular iron. There was no increased risk of SAEs with IV iron (relative risk [RR], 1.04; 95% CI, 0.93-1.17; I(2)=9%). Subgroup analysis revealed a decreased rate of SAEs when IV iron was used to treat heart failure (RR, 0.45; 95% CI, 0.29-0.70; I(2)=0%). Severe infusion reactions were more common with IV iron (RR, 2.47; 95% CI, 1.43-4.28; I(2)=0%). There was no increased risk of infections with IV iron. Gastrointestinal AEs were reduced with IV iron.

Conclusion: Intravenous iron therapy is not associated with an increased risk of SAEs or infections. Infusion reactions are more pronounced with IV iron.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Administration, Intravenous* / adverse effects
  • Administration, Intravenous* / methods
  • Anemia, Iron-Deficiency / drug therapy*
  • Drug-Related Side Effects and Adverse Reactions / classification
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Humans
  • Iron* / administration & dosage
  • Iron* / adverse effects
  • Outcome Assessment, Health Care
  • Randomized Controlled Trials as Topic


  • Iron