What are the risks associated with intravenous (IV) iron infusions?

From the Guidelines

Intravenous iron infusions carry risks, including infusion reactions, allergic reactions, and hypophosphatemia, but the vast majority of reactions are complement activation-related pseudo-allergy, which should be treated as such, and true anaphylaxis is very rare 1.

Risks Associated with IV Iron Infusions

The most common side effects of IV iron infusions include:

• Nausea
• Vomiting
• Headache
• Joint or muscle pain
• Temporary changes in taste At the injection site, patients may experience:
• Pain
• Redness
• Swelling
• Bruising More serious but less common risks include:
• Allergic reactions ranging from mild (itching, rash) to severe anaphylaxis (difficulty breathing, swelling of the face or throat, and drop in blood pressure) Some patients develop hypophosphatemia (low phosphate levels), which can cause weakness and bone pain, particularly with repeated dosing of iron carboxymaltose 1.

Management of Risks

To minimize the risks associated with IV iron infusions, it is essential to:

• Assess the risk of reaction before initiating the infusion, particularly in patients with a history of severe asthma or eczema, mastocytosis, multiple drug allergies, or prior reaction to IV iron 1
• Initiate the iron infusion at a slow rate, as slower infusion rates have been associated with lower infusion reactions 1
• Monitor the patient closely during the first 10 minutes of the infusion, as immediate infusion reactions occur during this time 1
• Be prepared to stop the infusion and seek medical attention if symptoms of a reaction occur 1

Special Considerations

Certain IV iron formulations have unique considerations, such as:

• Ferumoxytol, which is also approved as a magnetic resonance imaging contrast agent, and radiology should be notified if magnetic resonance imaging is obtained within 3 months after infusion 1
• Iron carboxymaltose, which has been associated with hypophosphatemia, particularly with repeated dosing, and should be used with great care in patients with poor absorption or nutrition 1

From the FDA Drug Label

The following additional adverse reactions have been identified with the use of Ferrlecit from postmarketing spontaneous reports: Cardiovascular System: shock, fetal bradycardia, injection site superficial thrombophlebitis, phlebitis, acute myocardial ischemia with or without myocardial infarction or with in-stent thrombosis in the context of a hypersensitivity reaction Gastrointestinal System: dysgeusia. Immune System: anaphylactic-type reactions. Nervous System: loss of consciousness, generalized convulsion, hypoesthesia. Skin and Appendages: skin discoloration, pallor. Individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events based on information from postmarketing spontaneous reports These adverse events included hypotension, nausea, vomiting, abdominal pain, diarrhea, dizziness, dyspnea, urticaria, chest pain, paresthesia, and peripheral swelling.

The risks associated with intravenous (IV) iron infusions include:

• Hypersensitivity reactions, such as anaphylaxis, which can be severe and life-threatening
• Cardiovascular events, including shock, fetal bradycardia, and acute myocardial ischemia
• Gastrointestinal symptoms, such as nausea, vomiting, and abdominal pain
• Nervous system effects, including loss of consciousness, generalized convulsion, and hypoesthesia
• Skin and appendage disorders, such as skin discoloration and pallor
• Increased risk of adverse events with individual doses exceeding 125 mg 2

From the Research

Risks Associated with Intravenous (IV) Iron Infusions

The use of intravenous iron has increased significantly in the last decade, but concerns remain about indications and administration 3. Some of the risks associated with IV iron infusions include:

• Hypersensitivity reactions, which can be life-threatening 4, 5, 6
• Anaphylaxis, which is a rare but serious adverse effect 4, 7
• Complement activation-related pseudo-allergy, which is a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response 4
• Minor infusion reactions, which are self-limited and due to labile iron 5
• Hypotension, which can occur during IV iron infusion and may be due to hypersensitivity or vascular reaction to labile iron 5

Risk Factors for Hypersensitivity Reactions

Several risk factors have been identified for hypersensitivity reactions to IV iron infusions, including:

• Previous reaction to an iron infusion 4, 6
• Fast iron infusion rate 4, 6
• Multiple drug allergies 4, 6
• Atopic diseases, such as asthma and urticaria 4, 6
• High serum tryptase levels 6
• Systemic inflammatory diseases 4

Management of IV Iron Infusions

To minimize the risks associated with IV iron infusions, it is recommended that:

• Patients be informed about infusion reactions and identified for increased risk of hypersensitivity or contraindications for IV iron 5
• Infusion be started at a low rate for a few minutes 5
• Staff be trained to evaluate and manage adverse reactions 5
• An algorithm be used to scale the intensity of treatment to the clinical picture and/or response to therapy 5