What are the side effects of intravenous iron infusion?

From the Guidelines

Iron infusions can cause several side effects, though most are mild and temporary, with true anaphylaxis being very rare, occurring in less than 1 in 200,000 administrations 1.

Common Side Effects

• Nausea
• Headache
• Joint or muscle pain
• Metallic taste in the mouth
• Pain, redness, swelling, or bruising at the infusion site
• Temporary drop in blood pressure, which can cause dizziness or lightheadedness

Rare but Serious Side Effects

• Allergic reactions (hives, itching, difficulty breathing), which typically occur within the first few minutes of infusion
• Delayed reactions, including fever and severe joint pain, occurring 1-2 days after treatment
• Iron infusions can temporarily darken skin or urine

Management of Side Effects

Most side effects resolve within 24-48 hours after infusion. If severe symptoms like chest pain, severe shortness of breath, or swelling of the face or throat occur, immediate medical attention is necessary as these could indicate a serious reaction requiring prompt treatment. The majority of reactions to intravenous iron are complement activation–related pseudo-allergy (infusion reactions) and should be treated as such 1. It is recommended that individuals administering intravenous iron have knowledge in intravenous iron administration, including pre-infusion assessment to evaluate infusion reaction risks, pre- and post-infusion monitoring, identification of and management of infusion reactions, accurate documentation of these reactions, laboratory monitoring, and recognition and management of treatment-emergent hypophosphatemia 1.

From the FDA Drug Label

Adverse reactions may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Venofer) which may cause fetal bradycardia, especially during the second and third trimester Among the breastfed infants, adverse reactions included constipation and diarrhea but none of the adverse reactions reported were considered related to ferric carboxymaltose exposure through breastmilk Monitor breastfed infants for gastrointestinal toxicity (constipation, diarrhea)

The common side effects of iron infusion include:

• Gastrointestinal toxicity such as constipation and diarrhea
• Severe adverse reactions including circulatory failure, severe hypotension, and shock
• Fetal bradycardia especially during the second and third trimester in pregnant women It is essential to monitor breastfed infants for gastrointestinal toxicity and to cautiously administer iron infusions to elderly patients due to potential decreased hepatic, renal, or cardiac function 2 3

From the Research

Iron Infusion Side Effects

• Hypersensitivity reactions (HSRs) are a known risk of intravenous (IV) iron formulations, with a small risk of severe reactions 4, 5, 6, 7, 8
• The risk of HSRs varies among different IV iron formulations, with ferric derisomaltose (FDI) having a lower risk compared to ferric carboxymaltose (FCM) and iron sucrose (IS) 4
• Modern iron formulations, such as iron dextran, iron derisomaltose, ferric carboxymaltose, ferumoxytol, iron sucrose, and sodium ferric gluconate, are associated with a risk of severe infusion reactions, although the risk is generally low (<1%) 5
• Hypophosphatemia is a potential complication of IV iron therapy, particularly with FCM, affecting 50-74% of patients in prospective clinical trials 5
• Severe adverse events, such as those requiring epinephrine, are rare, with only 2 documented cases associated with iron dextran in a study of over 12,000 patients 6
• Premedication and test doses are not necessary for IV iron infusions, and their use may be associated with a higher risk of adverse events 6
• The safety of recommencing an infusion or subsequent rechallenge following an infusion reaction to IV iron is generally good, with most patients tolerating the infusion or rechallenge 8

Comparison of Iron Formulations

• FCM is associated with a higher risk of hypersensitivity reactions compared to IS, but shows no significant difference in severe adverse events 7
• FDI has a lower risk of HSRs compared to FCM and IS 4
• Ferumoxytol and ferric carboxymaltose have a lower risk of adverse events compared to iron sucrose and iron dextran 6

Management of Infusion Reactions

• Recommencement of the index infusion is safe for patients with mild or moderate hypersensitivity reactions, and subsequent rechallenge to an alternative formulation is generally tolerated 8
• Rechallenge to the same formulation may be considered in some cases, depending on the risk-benefit profile 8