Is intravenous (IV) iron therapy safe for patients with intolerance to oral iron supplementation?

From the Guidelines

Iron infusion therapy is a safe and effective alternative for individuals who cannot tolerate oral iron supplementation, as it can rapidly improve hemoglobin levels and iron stores. According to a recent expert review published in Clinical Gastroenterology and Hepatology 1, intravenous (IV) iron is indicated for patients who cannot tolerate oral iron or have not responded to oral iron supplementation. This review highlights the importance of monitoring hemoglobin levels and iron stores before and after IV iron supplementation, with expected increases in hemoglobin levels by 1 g/dL within 2 weeks of supplementation.

Some key benefits of IV iron infusion include:

• Rapid improvement in hemoglobin levels and iron stores
• Ability to bypass the digestive system, reducing side effects associated with oral iron supplementation
• Effective for patients with impaired absorption, such as those with active inflammatory bowel disease (IBD) or after bariatric surgery
• Various formulations available, including iron sucrose, ferric carboxymaltose, and iron dextran, which can replace iron deficits with 1 to 2 infusions

While IV iron infusion is generally well-tolerated, potential side effects include:

• Temporary headaches
• Flushing
• Joint pain
• Rarely, serious allergic reactions, which are often idiosyncratic infusion reactions that can mimic allergic reactions As noted in the expert review 1, being truly allergic to IV iron is very rare, and most reactions can be managed by stopping the infusion and restarting at a slower rate or using corticosteroids for more severe reactions. Overall, IV iron infusion therapy is a safe and effective treatment option for individuals who cannot tolerate oral iron supplementation, and its benefits outweigh the potential risks.

From the FDA Drug Label

In patients with iron deficiency, red cell uptake of radiolabeled iron ranged from 91% to 99% at 24 days after Injectafer dose Trial 1: A Multi-center, Randomized, Active Controlled Study to Investigate the Efficacy and Safety of Intravenous Ferric Carboxymaltose (FCM) in Patients with Iron Deficiency Anemia (IDA), (NCT00982007) was a randomized, open-label, controlled clinical study in patients with IDA who had an unsatisfactory response to oral iron (Cohort 1) or who were intolerant to oral iron (Cohort 2) during the 14-day oral iron run-in period. Cohort 2 subjects were randomized to Injectafer or another IV iron per standard of care [90% of subjects received iron sucrose]. Table 5 shows the baseline and the change in hemoglobin from baseline to highest value between baseline and Day 35 or time of intervention.

Iron infusion therapy with Injectafer is safe for patients who can't tolerate oral iron supplementation. The clinical study results show that Injectafer is effective in increasing hemoglobin levels in patients with iron deficiency anemia who are intolerant to oral iron.

• The study found that Injectafer increased hemoglobin levels by 2.9 g/dL in Cohort 2, which consisted of patients who were intolerant to oral iron.
• The results also show that Injectafer is well-tolerated, with no significant differences in adverse events compared to other IV iron therapies 2.

From the Research

Safety of Iron Infusion Therapy

• Iron infusion therapy is generally considered safe for patients who cannot tolerate oral iron supplementation, with modern iron formulations having evolved to minimize risks 3.
• The risk of severe infusion reactions is associated with all iron preparations, but recent prospective clinical trials have shown that this risk is comparable among modern preparations, affecting less than 1% of patients 3.
• Intravenous iron therapy is typically reserved for patients with iron deficiency anemia who have intolerance or unresponsiveness to oral iron, or who require rapid correction of iron deficit 3, 4.

Potential Side-Effects

• Hypophosphatemia, or the 6H syndrome, is a potential complication of iron infusion therapy, particularly with ferric carboxymaltose, affecting 50-74% of patients in prospective clinical trials 3.
• This biochemical change can cause severe and potentially irreversible clinical complications, such as bone pain, osteomalacia, and fractures 3.
• Other potential side-effects of intravenous iron include infusion reactions, which can be anticipated and managed with proper education and preparation of staff and patients 4.

Clinical Context

• Iron infusion therapy is indicated for the treatment of iron deficiency when oral preparations are ineffective or cannot be used, and has applicability in a wide range of clinical contexts, including chronic inflammatory conditions, perioperative settings, and disorders associated with chronic blood loss 4, 5.
• Ferric carboxymaltose is a commonly used intravenous iron preparation that has been shown to be effective and generally well-tolerated in various patient populations with iron deficiency 5, 6.