Iron Injections

Background clinical information:

Iron deficiency (ID) is a broad term referring to low iron stores and is only classified as iron deficiency anaemia (IDA) when haemoglobin levels fall below certain cut-off values. The World Health Organization (WHO) has set these at 130 g/L in males, 120 g/L in non-pregnant females and 110g/L in pregnant females. (Al-Naseem, Sallam et al. 2021)

It is important to note that whilst iron deficiency anaemia is the most frequent presentation of iron deficiency, the two terms are neither synonymous nor interchangeable. Iron deficiency is a umbrella term referring to low iron stores that do not meet the body’s iron requirements, regardless of whether anaemia is present or not. (Al-Naseem, Sallam et al. 2021)

Importantly, the two conditions are diagnosed differently. Iron deficiency  is measured by a low ferritin, which is an intracellular iron storage protein responsible for ‘stock piling’ surplus iron once all cellular needs are met, and in presence of an acute demand, releases the stored iron.  (Kotla, Dutta et al. 2022).

In contrast, iron deficiency anaemia shows a low haemoglobin level.  (Patel 2025)  It is a more severe form of iron deficiency and sufferers can present with shortness of breath, syncope, and reduced exercise tolerance.

In clinical practice, when ferritin levels dip below 30 μg/L, an absolute iron deficiency exists. Aside from being an iron storage facility, ferritin is an acute-phase reactant that is increased in serum during chronic inflammation. Cut-off values for ferritin in iron deficiency  are increased to 100 μg/L in states of chronic inflammation. (Soppi 2018)

Generally, iron deficiency can be due to insufficient iron intake such as poor nutrition (Lucas and Garg 2024), decreased absorption, frequent blood donations, blood loss and chronic inflammation whilst iron deficiency anaemia is most often from blood loss, especially in older patients but is also seen in pregnancy, and in celiac disease. In short, iron deficiency anaemia is a late and more severe form of iron deficiency (Soppi 2018) (Al-Naseem, Sallam et al. 2021)

In Australia around 12 per cent of women, eight per cent of pre-school-aged children, and 20 per cent of people over 85 years are anaemic.

Treatment options:

Contemporary formulations of iron include ferric carboxymaltose (Ferinject®) and ferric derisomaltose (Monofer®). In these preparations, iron is bound within a large, complex carbohydrate shell which allows for a slow release of iron and permits large single doses to be given.

In contrast, the lack of popularity of iron sucrose (Venofer®) is due to the relative instability of the sucrose (carbohydrate) shell allowing only for a low infusion dose of 100mg. (Lucas and Garg 2024)

Dosing:

To replenish the iron stores the Ganzoni formula is used:

Total iron dose required (mg iron) = body weight (kg) X (target Hb – actual Hb- g/L) x 0.24 + 500mg (if ≥ 35kg).

NB: If the body weight is < 35kg, then add on 15mg/kg, not 500mg.

Iron sucrose (Venofer®) is TGA registered only as a single 100mg infusion due to its relative instability and is only for chronic haemodialysis patients receiving erythropoietin stimulating agents.

Ferinject® can be given as a rapid infusion of up to 1g of iron over 15 minutes and has a very low rate of infusion reaction of 0.2-1.7%, and anaphylaxis at < 1.0%. (Patel 2025) Monofer®, abbreviated to FDI (ferric derisomaltose) can be administered up to 1500mg over 30 minutes as a single infusion, hence it may only require one medical intervention. The incidence of adverse reactions for Monofer® is reported to be 0.54%.(Sivakumar, Jubb et al. 2019)

Benefits:

Ferinject®, abbreviated to FCM (ferric carboxymaltose), is profitably used in inflammatory bowel disease, upper gastrointestinal bleeding, chronic kidney disease (CKD), malignancy, perioperative bleed, perinatal iron deficiency anaemia and heavy uterine bleeding. It is superior to iron sucrose for improving Hb, ferritin, and transferrin saturation. The Hb rises by 20-30g/L inside eight weeks.  (Lyseng-Williamson and Keating 2009, Patel 2025). The dose can be given over 15 minutes for 1g. (Lucas and Garg 2024)

If a dose of Ferinject® greater then 1000mg is required, a seven-day interval is required. (Lucas and Garg 2024) (Patel, Thanvi et al. 2025).

Monofer® has a superior matrix structure which allows for higher single doses, hence causing a more rapid restoration of iron levels. 1g can be given over 20 minutes and 1500mg over 30 minutes as a single infusion. (Lucas and Garg 2024) The TGA has listed it as indicated when oral iron preparations are ineffective or cannot be used, or when there is a clinical need for the rapid delivery of iron. The diagnosis must be based on laboratory tests.

Irrespective of the form of IV iron chosen, substantial benefit has been shown in CKD, IBD and heart failure because elevated levels of hepcidin in these conditions prevent the beneficial absorption of oral iron. (Kaitha, Bashir et al. 2015, Gutiérrez 2021, Loncar, Obradovic et al. 2021)

Contraindications for Ferinject:

• Hypersensitivity to ferric carboxymaltose complex, to Ferinject or to any of its excipients
• Anaemia not attributed to iron deficiency, e.g. other microcytic anaemia
• Evidence of iron overload or disturbances in utilisation of iron.

Contraindications for Monofer:

• Hypersensitivity to the active substance, to Monofer or any of the excipients.
• Non-iron deficiency anaemia (e.g. haemolytic anaemia).
• Iron overload or disturbances in utilisation of iron (e.g. haemochromatosis, haemosiderosis).

Safety:

Of the two commonly used formulations, hypersensitivity reactions (HSRs) have been reported by Mulder, van den Hoek et al. (2019) to be 75% lower for Ferinject  compared to Monofer (RR = 0.248, CI: 0.145-0.426, P < 0.0001). Irrespective of the IV iron used, the presence of comorbidities raised the risk of HSRs by a factor of 3.6.

Moderate to severe hypersensitivity reactions occur at a rate of 0.2-1.7%. Mild reactions include urticaria, itching, rash, nausea and tachycardia. A slower rate of infusion and an antihistamine and/or corticosteroid treatment may allow the infusion to occur. True anaphylaxis to the aforementioned 3 products is estimated from clinical trials to be < 1%.

The more stable the carbohydrate which binds the iron core, the less likely minor infusion reactions will occur. (Gómez-Ramírez, Shander et al. 2019)

Around 1 in 100 people have a Fishbane reaction with Monofer, which can cause a flushed feeling. This is not an allergic reaction.

Research shows that the risk of hypophosphatemia differs between the two formulations of iron with the risk with ferric carboxymaltose (FCM) ranging from 47-57% whilst for ferric derisomaltose (FDI) the range is 4-8%. (Boots and Quax 2022)

Skin staining from IV iron, known as extravasation, can be permanent. In clinical trials it occurred at a rate of 1.3% (Lucas and Garg 2024)

Given that both formulations demonstrate rapid increases in haemoglobin, serum ferritin, and transferrin saturation, a decision as to which to use will be based on whether a dose more than 1000mg is needed, any prior history of hypophosphatemia, and cost (if any) to the patient and/or the health institution, be it a GP practice or hospital.

Conclusions:

• Monofer® causes less hypophosphatemia than Ferinject® but has a higher of ADRs.
• A higher iron dose of Monofer® can be given compared to Ferinject® because Monofer® is a more stable carbohydrate-based iron-embedded molecule.
• Iron deficiency anaemia is the most severe presentation of iron deficiency, but the two terms are neither synonymous nor interchangeable.