When should intravenous (IV) iron repletion be considered over oral iron supplementation?

From the Guidelines

Intravenous (IV) iron repletion should be considered over oral iron supplementation in patients who cannot tolerate oral iron, have impaired absorption, or require rapid iron repletion, as evidenced by the most recent study in 2024 1. When considering IV iron repletion, several factors come into play, including the severity of iron deficiency anemia, the presence of malabsorption conditions, ongoing blood loss, and intolerance to oral iron preparations.

• IV iron is preferred for patients with severe iron deficiency anemia, malabsorption conditions such as celiac disease, inflammatory bowel disease, or post-bariatric surgery, and those with ongoing blood loss exceeding the rate of oral iron absorption.
• It is also indicated when rapid iron repletion is needed, such as in late pregnancy, preoperatively for anemic patients, or in patients with chronic kidney disease on erythropoietin therapy, as supported by studies in 2019 1 and 2016 1.
• Common IV iron formulations include iron sucrose, ferric carboxymaltose, and iron dextran, with ferric carboxymaltose being a preferred option due to its ability to deliver large single doses, as noted in the 2022 ESPEN micronutrient guideline 1.
• The choice of IV iron formulation depends on patient and doctor preferences, formulation availability, cost, and comorbidities, with the most recent carbohydrate products being recommended for their safety and efficacy, as stated in the 2022 ESPEN micronutrient guideline 1.
• Patients should be monitored for infusion reactions, which are rare with newer preparations but can include hypotension, arthralgias, or anaphylaxis, as cautioned in the 2015 European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases 1.

From the FDA Drug Label

Inclusion criteria prior to randomization included hemoglobin (Hb) <12 g/dL, ferritin ≤100 ng/mL or ferritin ≤300 ng/mL when transferrin saturation (TSAT) ≤30%. Cohort 1 subjects were randomized to Injectafer or oral iron for 14 more days Cohort 2 subjects were randomized to Injectafer or another IV iron per standard of care [90% of subjects received iron sucrose]. The primary etiologies of IDA were heavy uterine bleeding (47%) and gastrointestinal disorders (17%)

Consider IV iron repletion over oral iron supplementation in patients with:

• Intolerance to oral iron
• Unsatisfactory response to oral iron
• Heavy uterine bleeding or gastrointestinal disorders as the primary etiology of iron deficiency anemia (IDA)
• Non-dialysis dependent chronic kidney disease with IDA
• Iron deficiency and chronic heart failure with left ventricular ejection fraction of < 45% and New York Heart Association (NYHA) class II/III 2 2

From the Research

Indications for IV Iron Repletion

IV iron repletion should be considered over oral iron supplementation in the following situations:

• When oral iron preparations are ineffective or cannot be used 3
• In cases of chronic inflammatory conditions, perioperative settings, and disorders associated with chronic blood loss 3
• When there is a need for rapid iron repletion, such as in patients with severe iron deficiency anemia or those requiring erythropoiesis-stimulating agents (ESAs) 4
• In patients with intolerance or unresponsiveness to oral iron 5
• When the time available for iron replenishment is limited 3

Patient-Specific Factors

The decision to use IV iron repletion should also take into account patient-specific factors, such as:

• Presence of inflammation, which can affect iron metabolism and response to treatment 3, 5
• Anticipated risk of side-effects or intolerance to oral iron 3
• Underlying disease or condition, such as chronic kidney disease, gastrointestinal disease, or heavy menstrual bleeding 3, 6

Safety and Efficacy

IV iron preparations have been shown to be effective and safe for use in various clinical settings, with a low risk of adverse effects 6, 4, 5. However, it is essential to select the appropriate iron therapy and evaluate treatment response to minimize the risk of complications, such as hypophosphatemia and related biochemical changes 5.