Skip to main content
SpringerLink
Log in

Brand ferumoxytol vs. generic ferumoxytol comparison across two dosing regimens: a cardiac MRI image quality study

  • Original Article
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Background

Ferumoxytol is becoming more widely used as an off-label blood-pool contrast agent for MR angiography (MRA) and four-dimensional (4D) flow imaging in pediatric cardiovascular disease. Brand and generic versions of ferumoxytol are available with no information on relative efficacy as a contrast agent and safety profiles.

Objective

This study evaluates patient safety and image quality of comparable dosages of generic ferumoxytol (GF) versus brand ferumoxytol (BF) with the following hypotheses: (1) Reducing the contrast dosage from 3 to 2 mg/kg will not affect imaging quality and diagnostic accuracy of MRA and four-dimensional 4D flow. (2) GF and BF have similar image quality. (3) GF and BF have similar patient safety profiles.

Materials and methods

In an IRB-approved retrospective study, changes in vitals/clinical status between baseline, during infusion, and 30 min post-infusion were analyzed in 3 groups: group 1 (3 mg/kg BF, 216 patients, age: 19.29 ± 11.71 years ranging from 2 months to 62 years), group 2 (2 mg/kg BF, 47 patients, age: 15.35 ± 8.56 years ranging from 10 days to 41 years), and group 3 (2 mg/kg GF, 127 patients, age: 17.16 ± 12.18 years ranging from 6 days to 58 years). Both pediatric and adult patients with congenital heart disease (CHD) indications were included within the study. Adverse reactions were classified as mild, moderate, or severe. Quantitative analysis of MR image quality was performed with signal-to-noise ratio (SNR) on MRA and velocity-to-noise ratio (VNR) on 4D flow. Qualitative grading of imaging features was performed by 2 experienced observers. Two-way analysis of variance (ANOVA) and chi-square tests were used for comparison with a P value of ≤ 0.05 used for significance.

Results

No statistical difference was found in clinical status and vital signs (P>0.05). No severe reactions were reported. 7.9% of GF patients experienced an adverse reaction compared to 2.3% with 3 mg/kg BF and 8.4% with 2 mg/kg BF. There was no statistical difference in SNR between the 3 groups (P>0.05). For 4D flow, 2 mg/kg GF demonstrated an increase in VNR compared to 2 mg/kg BF (P = 0.005). The qualitative scores for MRA and 4D flow were high (≥ 3) across all 3 groups.

Conclusions

No significant difference was identified between 2 mg/kg GF and BF in terms of safety profile and image quality. Given the small sample size of this study, further studies are required to confirm these results.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author (RK) upon reasonable request.

References

  1. Jin R, Lin B, Li D, Ai H (2014) Superparamagnetic iron oxide nanoparticles for MR imaging and therapy: design considerations and clinical applications. Curr Opin Pharmacol 18:18–27

    Article  CAS  PubMed  Google Scholar 

  2. Corot C, Robert P, Idée JM, Port M (2006) Recent advances in iron oxide nanocrystal technology for medical imaging. Adv Drug Deliv Rev 58:1471–1504

    Article  CAS  PubMed  Google Scholar 

  3. Balakrishnan VS, Rao M, Kausz AT et al (2009) Physicochemical properties of ferumoxytol, a new intravenous iron preparation. Eur J Clin Invest 39:489–496

    Article  CAS  PubMed  Google Scholar 

  4. Toth GB, Varallyay CG, Horvath A et al (2017) Current and potential imaging applications of ferumoxytol for magnetic resonance imaging. Kidney Int 92:47–66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ruangwattanapaisarn N, Hsiao A, Vasanawala SS (2015) Ferumoxytol as an off-label contrast agent in body 3T MR angiography: a pilot study in children. Pediatr Radiol 45:831–839

    Article  PubMed  Google Scholar 

  6. Cheng JY, Hanneman K, Zhang T et al (2016) Comprehensive motion-compensated highly accelerated 4D flow MRI with ferumoxytol enhancement for pediatric congenital heart disease. J Magn Reson Imaging 43:1355–1368

    Article  PubMed  Google Scholar 

  7. Kowalczyk M, Banach M, Rysz J (2011) Ferumoxytol: a new era of iron deficiency anemia treatment for patients with chronic kidney disease. J Nephrol 24:717–722

    Article  CAS  PubMed  Google Scholar 

  8. Hetzel D, Strauss W, Bernard K, Li Z, Urboniene A, Allen LF (2014) A Phase III, randomized, open-label trial of ferumoxytol compared with iron sucrose for the treatment of iron deficiency anemia in patients with a history of unsatisfactory oral iron therapy. Am J Hematol 89:646–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Finn JP, Nguyen KL, Han F et al (2016) Cardiovascular MRI with ferumoxytol. Clin Radiol 71:796–806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Pai AB, Garba AO (2012) Ferumoxytol: a silver lining in the treatment of anemia of chronic kidney disease or another dark cloud? J Blood Med 3:77–85

    PubMed  PubMed Central  Google Scholar 

  11. Food & Drug Administration. FDA Drug Safety Communication: FDA strengthens warnings and changes prescribing instructions to decrease the risk of serious allergic reactions with anemia drug Feraheme (ferumoxytol). Available: http://www.fda.gov/Drugs/DrugSafety/ucm440138.htm. Accessed 28 Sept 2023

  12. Nguyen KL, Yoshida T, Kathuria-Prakash N et al (2019) The rise of off-label iron-based agents in magnetic resonance imaging. J Radiol Nurs 38:https://doi.org/10.1016/j.jradnu.2018.11.004

  13. Vasanawala SS, Nguyen KL, Hope MD et al (2016) Safety and technique of ferumoxytol administration for MRI. Magn Reson Med 75:2107–2111

    Article  PubMed  PubMed Central  Google Scholar 

  14. Dahl NV, Kaper RF, Strauss WE, Corvino FA, Zivkovic M (2017) Cost-effectiveness analysis of intravenous ferumoxytol for the treatment of iron deficiency anemia in adult patients with non-dialysis-dependent chronic kidney disease in the USA. Clinicoecon Outcomes Res 9:557–567

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lim W, Afif W, Knowles S et al (2019) Canadian expert consensus: management of hypersensitivity reactions to intravenous iron in adults. Vox Sang 114:363–373

    Article  PubMed  PubMed Central  Google Scholar 

  16. 2021 ACR Manual on Contrast Media. 10.3. American College of Radiology, pp 100–101. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf. Accessed 28 Sept 2023

  17. Rampton D, Folkersen J, Fishbane S et al (2014) Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica 99:1671–1676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Nilsson A, Markenroth Bloch K et al (2012) Variable velocity encoding in a three-dimensional, three-directional phase contrast sequence: evaluation in phantom and volunteers. J Magn Reson Imaging 36:1450–1459

    Article  PubMed  Google Scholar 

  19. Zhou Z, Han F, Rapacchi S et al (2017) Accelerated ferumoxytol-enhanced 4D multiphase, steady-state imaging with contrast enhancement (MUSIC) cardiovascular MRI: validation in pediatric congenital heart disease. NMR Biomed 30

  20. Kanda T, Oba H, Toyoda K, Kitajima K, Furui S (2016) Brain gadolinium deposition after administration of gadolinium-based contrast agents. Jpn J Radiol 34:3–9

    Article  CAS  PubMed  Google Scholar 

  21. Storey P, Lim RP, Chandarana H et al (2012) MRI assessment of hepatic iron clearance rates after USPIO administration in healthy adults. Invest Radiol 47:717–724

    Article  CAS  PubMed  Google Scholar 

  22. Worm M, Francuzik W, Renaudin J-M et al (2018) Factors increasing the risk for a severe reaction in anaphylaxis: an analysis of data from The European Anaphylaxis Registry. Allergy 73:1322–1330

    Article  CAS  PubMed  Google Scholar 

  23. Assessment report for: Iron containing intravenous (IV) medicinal products. (2013) EMA/549569/2013

Download references

Author information

Authors and Affiliations

  1. Department of Radiology, Nationwide Children’s Hospital, Columbus, OH, USA

    Anoushka Dasi, Donna N. Kring, Bhavani Selvaraj, Patricia Morgan, Christopher Gerity, Eric E. Morgan, Ramkumar Krishnamurthy & Rajesh Krishnamurthy

  2. The Ohio State University, Columbus, OH, USA

    Anoushka Dasi & Rajesh Krishnamurthy

Authors
  1. Anoushka Dasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donna N. Kring
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bhavani Selvaraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patricia Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher Gerity
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eric E. Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ramkumar Krishnamurthy
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rajesh Krishnamurthy
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh Krishnamurthy.

Ethics declarations

Declarations

All human and animal studies have been approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. IRB approval was obtained for this retrospective study.

Conflicts of interest

None

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dasi, A., Kring, D.N., Selvaraj, B. et al. Brand ferumoxytol vs. generic ferumoxytol comparison across two dosing regimens: a cardiac MRI image quality study. Pediatr Radiol 53, 2622–2632 (2023). https://doi.org/10.1007/s00247-023-05778-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-023-05778-4

Keywords

Search

Navigation