What is the risk of seizure with iron infusion?

From the Guidelines

The risk of seizures with iron infusions is very low but does exist as a rare adverse event, with an estimated incidence of less than 1% of all infusions, as reported in recent studies 1. Seizures are most commonly associated with rapid administration of iron dextran or iron sucrose. Patients with a history of seizure disorders, neurological conditions, or electrolyte abnormalities may be at higher risk. The mechanism behind iron infusion-related seizures likely involves rapid changes in serum iron levels or hypersensitivity reactions that affect the central nervous system. To minimize this risk, healthcare providers should administer iron infusions at the recommended rate, perform test doses when indicated (particularly with iron dextran), and closely monitor patients during and after administration. Some key points to consider when administering iron infusions include:

• Newer iron formulations such as ferric carboxymaltose (Injectafer) and ferumoxytol (Feraheme) appear to have lower rates of seizure complications compared to older preparations 1.
• If a patient experiences neurological symptoms during an infusion, the administration should be stopped immediately and appropriate medical intervention provided.
• The use of intravenous iron has become an essential component for the treatment of iron deficiency and iron deficiency anemia, with newer formulations allowing for a total dose infusion in 15 to 60 min, obviating multiple unnecessary visits for the same clinical benefit without added toxicity 1. It is essential to follow the recommended guidelines for the administration of intravenous iron, including pre- and post-infusion monitoring, identification, and classification of infusion reactions, and recognition and management of treatment-emergent hypophosphatemia 1.

From the FDA Drug Label

Nervous System: loss of consciousness, generalized convulsion, hypoesthesia The risk of seizure with iron infusion is noted in the drug label as generalized convulsion, which is a type of seizure. This adverse event has been identified with the use of Ferrlecit from postmarketing spontaneous reports 2.

• Seizure risk: The label does mention generalized convulsion as a possible adverse reaction, indicating a risk of seizure with iron infusion.
• Key consideration: Individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events, including those affecting the nervous system.

From the Research

Risk of Seizure with Iron Infusion

• The risk of seizure with iron infusion is not directly addressed in most of the provided studies, which focus on hypersensitivity reactions, hypophosphatemia, and the treatment of iron deficiency anemia in various patient populations 3, 4, 5.
• However, one study suggests that iron itself may play a role in the development of seizures, as cortical iron injection induced recurrent seizures in animal models 6.
• Another study found that iron deficiency and iron deficiency anemia were more frequent in children with seizures, suggesting a possible link between iron status and seizure risk 7.
• It is essential to note that the provided studies do not establish a direct causal relationship between iron infusion and seizure risk, and more research is needed to fully understand this potential association 3, 4, 5, 6, 7.

Hypersensitivity Reactions and Iron Infusion

• Hypersensitivity reactions to intravenous iron are rare but can be life-threatening, and major risk factors include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases 3.
• The management of iron infusions requires meticulous observation, and prompt recognition and severity-related interventions by well-trained medical and nursing staff are crucial in the event of an adverse reaction 3.

Iron Deficiency and Seizure Risk

• Iron deficiency and iron deficiency anemia may be more frequent in children with seizures, and evaluating iron status in children with a first attack of febrile or afebrile seizures is recommended 7.
• The exact mechanism by which iron deficiency may contribute to seizure risk is not fully understood and requires further investigation 7.