As IV iron preparation have become safer, they are increasingly being used. However, the oral route is still best, when possible. Ferraheme is the latest IV iron entrant. Feraheme™ (ferumoxytol) Injection is indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). There are four commercially available i.v. iron products, iron dextran, iron sucrose, and iron ferric gluconate, or Ferrlecit and Ferraheme. The use of iron dextran has decreased because of the risk of anaphylaxis. Iron sucrose recently received Food and Drug Administration (FDA)-approved labeling for the treatment of iron deficiency anemia in NDDCKD patients, making it the first of the non-dextran iron supplements to receive such approval. Before this approval, both iron sucrose and iron ferric gluconate were indicated only for the treatment of iron deficiency in dialysis patients. Ferrlecit is FDA approved for treating iron deficiency anemia in patients undergoing hemodialysis who are also receiving epoetin therapy.

 Anemia is a common complication of kidney disease. Although erythropoietin deficiency is the most important cause of anemia in patients with kidney disease, iron deficiency is common and can complicate treatment by causing a relative resistance to epoetin alfa therapy. I.V. iron is widely used in hemodialysis patients but less so in patients with non-dialysis-dependent chronic kidney disease (NDDCKD). Although oral iron can be used in the latter patients, its use is limited by adverse effects, poor compliance, and the long time period required to replete iron stores.

Indications for the use of intravenous iron include chronic uncorrectable bleeding, intestinal malabsorption, intolerance to oral iron, nonadherence, or a hemoglobin level less than 6 g per dL (60 g per L) with signs of poor perfusion in patients who would otherwise receive transfusion (e.g., those who have religious objections). Until recently, iron dextran (Dexferrum) has been the only parenteral iron preparation available in the United States. Unlike ther IV iron preparations it is approved for anemia of iron deficiency. The advantage of iron dextran over Ferrlecit is the ability to administer large doses (200 to 500 mg) at one time. One major drawback of iron dextran is the risk of anaphylactic reactions that can be fatal. There also is a delayed reaction, which consists of myalgias, headache, and arthralgias, that can occur 24 to 48 hours after infusion. Nonsteroidal anti-inflammatory drugs will usually relieve these symptoms, but they may be prolonged in patients with chronic inflammatory joint disease.

In conclusion, Venofer and Ferrlecit  is not FDA approved for iron deficiency but for dialysis only. This is because the dialysis group is the largest iron deficency group in the USA and is the group in which FDA required studies had beeen conducted. Off-label use of Venofer or Ferrlecit  is appropriate when oral iron was not tolerated. Iron extran is FDA approved for iron deficiency in general.

When oral iron did not work, IV iron in the dose and schedule proposed is medically appropriate. However, Feraheme™ (ferumoxytol) Injection is indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). The recommended dose of Feraheme is an initial 510 mg intravenous injection followed by a second 510 mg intravenous injection 3 to 8 days later. SINCe it is being given for an indiviudla without kidney disease, it is off-label. Ia gree with the denila of Ferroheme, but other IV prearations that are specifically indicated for iron deficiency alone, are acceptable. A number of IV iron formulations are available, including ferric carboxymaltose (FCM), ferric gluconate (FG), ferumoxytol, iron sucrose (IS), iron isomaltoside (termed ferric derisomaltose in the United States and Australia), and low molecular weight iron dextran (LMW ID). Monoferic and iron dexstran are FDA approved in adults patients who have an intolerance or had unsatisfactory response to oral iron or or who have non-hemodialysis dependent chronic kidney disease (CKD).

Scott B. Silverstein, Intravenous Iron Therapy: A Summary of Treatment Options and Review of Guidelines, Journal of Pharmacy Practice December 2008 vol. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015; 372:1832.

Lu M, Cohen MH, Rieves D, Pazdur R.
FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease.
Am J Hematol. 2010 May;85(5):315-9.

Ferreiro-Iglesias R, Barreiro-de-Acosta M, Seijo-Ríos S, Lorenzo A, Domínguez-Muñoz JE.
Efficacy of intravenous iron in treating iron deficiency anaemia in patients with inflammatory bowel disease. Are there predictors of response? [Article in English, Spanish]Rev Esp Enferm Dig. 2011 May;103(5):245-9.

Breymann C, Milman N, Mezzacasa A, et al. Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP). J Perinat Med 2016.

Abdulrehman J, Tang GH, Auerbach M, et al. The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta-analysis. Transfusion 2019; 59:3646.Breymann C, Milman N, Mezzacasa A, et al. Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP). J Perinat Med 2016.

Abdulrehman J, Tang GH, Auerbach M, et al. The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta-analysis. Transfusion 2019; 59:3646.

Macdougall IC, Strauss WE, McLaughlin J, Li Z, Dellanna F, Hertel J. A randomized comparison of ferumoxytol and iron sucrose for treating iron deficiency anemia in patients with CKD. Clin J Am Soc Nephrol. 2014;9(4):705–712. Onken JE, Bregman DB, Harrington RA, et al. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrol Dial Transplant. 2014;29(4):833-842.

Onken JE, Bregman DB, Harrington RA, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014;54(2):306-315.

REFERENCES:  

National Institute of Diabetes, Digestive and Kidney Diseases. Hemochromatosis.Last Update: March 2014. Available at: http://digestive.niddk.nih.gov/ddiseases/pubs/hemochromatosis/ Accessed March 24, 2016.

 Bruce R Bacon, et al, Diagnosis and Management of Hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011 Jul; 54(1): 328–343.

 Bardou-Jacquet E, Morcet J, Manet G, et al. Decreased cardiovascular and extrahepatic cancer-related mortality in treated patients with mild HFE hemochromatosis. J Hepatol 2015; 62:682.