What are the side effects of intravenous (IV) ferric carboxymaltose (FCM) in pregnant women with iron deficiency anemia?

Side Effects of Intravenous Ferric Carboxymaltose (FCM) in Pregnancy

Intravenous ferric carboxymaltose is generally safe and well-tolerated in pregnant women with iron deficiency anemia, with mild adverse events occurring in only 7-8% of patients and no serious treatment-related complications reported in multiple studies. 1, 2

Common Adverse Effects

The side effect profile of IV FCM in pregnancy is reassuringly benign:

• Mild adverse events occur in 7.8-20% of pregnant women, with most being non-serious and self-limiting 1, 2, 3
• Gastrointestinal symptoms are the most frequently reported, though significantly less common than with oral iron 2
• Minor infusion-related reactions may include transient discomfort at the infusion site 3
• No serious adverse drug reactions have been documented in large observational studies of pregnant women receiving FCM 1, 4

Serious but Rare Risks

While uncommon, clinicians must be aware of potentially life-threatening complications:

• Severe hypersensitivity reactions including anaphylaxis can occur, though they are extremely rare 5
• Fetal bradycardia may result from maternal severe hypersensitivity reactions or circulatory collapse, particularly in the second and third trimesters 5
• Hypotension and shock in the context of anaphylactic reactions represent the most serious maternal risk 5

Critical Safety Precautions

• Observe patients for at least 30 minutes following each IV injection for signs of adverse reactions 6
• Resuscitation facilities must be immediately available during all IV iron administrations 6
• Stop treatment immediately if signs of hypersensitivity develop 5

Treatment-Emergent Hypophosphatemia

A specific concern with FCM that differs from other IV iron formulations:

• FCM can cause significant hypophosphatemia through increased intact FGF23 (fibroblast growth factor 23), leading to renal phosphate wasting 6
• This side effect is unique to FCM compared to other IV iron preparations and has raised ongoing safety concerns 6
• Monitoring phosphate levels should be considered in patients requiring repeat courses within 3 months, though universal monitoring is not recommended 6
• Hypophosphatemia is typically asymptomatic and self-limiting in most patients, but any patient reporting bone pain should undergo imaging 6
• Phosphate supplementation should be avoided as it paradoxically worsens hypophosphatemia by raising parathyroid hormone 6

Contraindications in Pregnancy

FCM should not be used in the following situations:

• Known hypersensitivity to FCM or any of its excipients 5
• Previous serious hypersensitivity to other parenteral iron products 6
• Anemia not due to iron deficiency (e.g., other microcytic anemias) 6
• Evidence of iron overload or disturbances in iron utilization 6
• Hemoglobin levels >15 g/dL, as safety and efficacy have not been established in this population 6

Use with Caution

• Acute or chronic infection: Treatment should be stopped in patients with ongoing bacteremia 6
• First trimester: While not absolutely contraindicated, most studies have focused on second and third trimester use 1, 2, 4, 3, 7

Fetal Safety Profile

The evidence regarding fetal outcomes is reassuring:

• No adverse fetal outcomes were observed in comparative studies between FCM-treated and control groups 1
• Fetal heart rate monitoring during infusions showed no drug-related negative impact on the fetus 3
• No differences in fetal outcomes were found when comparing FCM to other iron treatments 7
• Published data are insufficient to definitively establish or exclude any drug-related risk for major birth defects or miscarriage, though available evidence is reassuring 5

Comparative Safety

When compared to alternatives:

• FCM has a comparable safety profile to iron sucrose but offers higher dosing convenience 2
• Both IV iron formulations are better tolerated than oral iron, which causes gastrointestinal side effects in up to 60% of patients 6
• Mild adverse events with FCM (7.8%) are actually lower than with iron sucrose (10.7%) in head-to-head comparisons 2

Clinical Context

Despite the theoretical risks, the real-world safety data is compelling:

• In a large retrospective study of 1,001 pregnant women, only 0.7% reported mild, non-serious adverse events 4
• No treatment-related adverse events were reported in a case-control study of 64 pregnant women receiving FCM 1
• The benefits of treating maternal iron deficiency anemia (preventing preterm delivery, low birth weight, postpartum anemia) must be weighed against the small risk of adverse reactions 5