What are the contraindications and potential side effects of iron infusion that need to be discussed with a patient (pt)?

Contraindications and Side Effects of Iron Infusion

Iron infusion should be avoided in patients with active severe infection and those with a history of serious hypersensitivity reactions to parenteral iron products, while patients must be counseled about the risk of acute infusion reactions (occurring in approximately 4% of cases), hypophosphatemia (affecting 50-74% with certain formulations), and rare but potentially life-threatening anaphylaxis. 1, 2

Absolute Contraindications

Active severe infection is the primary contraindication for intravenous iron therapy:

• Animal studies demonstrate that intravenous iron is harmful in the presence of severe infection, and it should be used with extreme caution, if at all, in patients with active infection 1
• While observational studies in hemodialysis patients showed associations between ferritin levels >4500 ng/ml and infections, randomized trials have not confirmed increased infection rates with IV iron, though these studies had limited power 1

Known hypersensitivity to the specific iron formulation or its components:

• Patients with prior serious reactions to parenteral iron products should not receive the same formulation 3, 4
• Iron dextran carries a boxed FDA warning regarding anaphylaxis risk and requires a test dose prior to full administration 1

Major Side Effects to Discuss

Acute Infusion Reactions (Most Common)

Infusion-related adverse events occur in approximately 4.3% of patients receiving intravenous iron 1:

• Anaphylactoid reactions (hypersensitivity-mediated, though not true IgE-mediated anaphylaxis in most cases) 1
• Hypotension requiring fluid resuscitation 1, 3, 5
• Shortness of breath and dyspnea 1, 3
• Chills and flushing 1, 3
• Nausea, vomiting, and abdominal pain 3
• Chest pain and paresthesias 3, 5

Iron dextran (especially high-molecular-weight formulations) carries the highest risk of anaphylactoid reactions compared to non-dextran preparations like ferric gluconate or iron sucrose 1. Modern formulations (ferric carboxymaltose, iron sucrose, ferric gluconate) have severe infusion reaction rates affecting <1% of patients in prospective trials 2, 6.

Hypophosphatemia (Emerging Concern)

Ferric carboxymaltose specifically causes hypophosphatemia in 50-74% of patients in prospective clinical trials 2:

• This represents the "6H syndrome": hyperphosphaturic hypophosphatemia triggered by high fibroblast growth factor 23 (FGF23) 2
• Leads to hypovitaminosis D, hypocalcemia, and secondary hyperparathyroidism 2
• Can cause severe clinical complications including bone pain, osteomalacia, and fractures that may be irreversible 2
• This formulation-specific toxicity should prompt consideration of alternative IV iron preparations when repeated dosing is anticipated 2, 6

Rare but Serious Complications

True anaphylaxis is very rare but potentially life-threatening 1, 7, 2:

• Resuscitation facilities must be available when administering IV iron 8
• Patients should be monitored for 60 minutes after initial infusion 8
• Symptoms include severe hypotension, shock, loss of consciousness, and generalized convulsions 3

Cardiovascular events reported in post-marketing surveillance 3:

• Acute myocardial ischemia with or without myocardial infarction 3
• In-stent thrombosis in the context of hypersensitivity reactions 3
• Fetal bradycardia in pregnant women (particularly second and third trimesters) 3

Other notable adverse effects:

• Skin discoloration and staining at injection sites 3, 6
• Superficial thrombophlebitis 3
• Dysgeusia (taste disturbance) 3

Formulation-Specific Considerations

Iron dextran requires special precautions:

• FDA boxed warning for anaphylaxis 1
• Mandatory test dose before full administration 1, 9
• Higher incidence of severe reactions compared to non-dextran formulations 1

Non-dextran preparations (iron sucrose, ferric gluconate, ferric carboxymaltose):

• No test dose required 1
• Lower risk of anaphylactoid reactions 1
• Iron sucrose and ferric gluconate have excellent safety profiles in primary care settings 5
• Ferric carboxymaltose has unique hypophosphatemia risk 2, 6

Special Population Warnings

Pregnancy:

• Severe hypersensitivity reactions can cause fetal bradycardia and circulatory failure 3
• Benzyl alcohol (preservative in some formulations like ferric gluconate) should be avoided due to risks in premature neonates 3
• Consider alternative iron formulations without benzyl alcohol 3

Pediatric patients:

• Ferric gluconate is not approved for neonates or infants due to benzyl alcohol toxicity risk 3
• "Gasping syndrome" has occurred in premature neonates receiving benzyl alcohol-containing drugs 3

Clinical Monitoring Requirements

Before administration:

• Screen for active infection (defer treatment if present) 1
• Obtain history of prior reactions to parenteral iron 3, 4
• Ensure resuscitation equipment is immediately available 8

During infusion:

• Monitor vital signs and observe for signs of hypersensitivity 3, 4
• Slow infusion rate if flushing or paresthesias develop 5
• Have emergency medications readily accessible 8

Post-infusion:

• Observe for at least 60 minutes after initial dose 8
• Monitor phosphate levels when using ferric carboxymaltose 2, 6
• Avoid iron overload by monitoring transferrin saturation (target <50%) and ferritin (target <800 μg/L) 9