Can FCM Injection Cause Anaphylaxis?
Yes, ferric carboxymaltose (FCM) can cause anaphylaxis, but this is an extremely rare occurrence. 1 Like all intravenous iron formulations, FCM carries a risk of severe life-threatening reactions including anaphylaxis, which constitutes a true medical emergency requiring immediate management with epinephrine. 1
Risk Profile and Incidence
Anaphylaxis with FCM is exceedingly uncommon. In a large randomized trial comparing FCM to ferumoxytol involving nearly 2,000 patients, no cases of anaphylaxis were reported in either treatment group. 2
The overall incidence of moderate-to-severe hypersensitivity reactions (HSRs) with FCM is approximately 0.7%, which is comparable to other modern intravenous iron formulations. 2
FCM demonstrates a favorable safety profile compared to iron dextran formulations. In direct comparative trials, FCM resulted in significantly fewer immune system disorders (0% vs 10.3%, P=0.003) and skin disorders (7.3% vs 24.4%, P=0.004) compared to iron dextran. 3
Contraindications and High-Risk Populations
FCM is contraindicated in patients with: 1
- Known hypersensitivity to FCM or any of its excipients
- Known serious hypersensitivity to other parenteral iron products
- Evidence of iron overload or disturbances in iron utilization
Patients at increased risk for hypersensitivity reactions include: 1
- Those with known drug allergies, particularly severe asthma, eczema, or other atopic allergies
- Patients with immune or inflammatory conditions (systemic lupus erythematosus, rheumatoid arthritis)
- Those with a history of previous reactions to iron preparations
Administration and Monitoring Requirements
Proper administration technique is critical to minimize reaction risk: 1
- FCM should be administered in settings where staff are trained and equipped to monitor for and manage hypersensitivity reactions
- Patients must be observed for adverse effects for at least 30 minutes following each intravenous injection 1
- The maximum recommended cumulative dose is 1000 mg of iron per week 1
However, the 30-minute observation period lacks physiological justification, as intravenous iron is not associated with severe delayed reactions. 1 Patients should instead be informed about possible delayed infusion reactions (flu-like symptoms, arthralgias, myalgias, fever) that can occur hours to days after infusion and typically resolve within 24 hours with NSAIDs. 1
Management of Anaphylaxis
If anaphylaxis occurs with FCM, it should be managed identically to anaphylaxis from any cause: 1
- Immediate administration of epinephrine is the drug of choice 4
- Discontinue the infusion immediately
- Provide supportive care as needed
- Document the reaction thoroughly for future reference 1
Important Clinical Caveat: Hypophosphatemia Risk
While anaphylaxis is rare, FCM carries a significant and unique risk of treatment-emergent hypophosphatemia that clinicians must recognize: 1
- The incidence of hypophosphatemia with FCM ranges between 47-75%, compared to <10% with other formulations 1
- In the PHOSPHARE-IBD trial, 51% of FCM-treated patients developed hypophosphatemia (<2 mg/dL) by Day 35 1
- FCM should be avoided in patients requiring repeat infusions (recurrent blood loss, malabsorptive disorders, inflammatory bowel disease, bariatric surgery) as it may lead to osteomalacia and fractures 1
- Hypophosphatemia with FCM can be severe and prolonged, lasting up to 6 months 1
Desensitization Option
For patients with a documented history of hypersensitivity reactions to iron preparations who require FCM, successful desensitization protocols exist. 5 A one-bag 8-step desensitization protocol with 500 mg FCM has been successfully completed in patients with prior anaphylaxis to iron preparations, with no hypersensitivity reactions observed during or after the procedure. 5