Ferric Carboxymaltose for Iron Deficiency Anemia
Primary Recommendation
Ferric carboxymaltose is the preferred first-line intravenous iron formulation for treating iron deficiency anemia when oral iron fails, is not tolerated, or in patients with chronic heart failure, inflammatory bowel disease, chronic kidney disease, or hemoglobin below 10 g/dL requiring rapid correction. 1, 2
When to Use Ferric Carboxymaltose Over Oral Iron
Absolute indications for FCM include:
- Intolerance to oral iron (gastrointestinal side effects are common with oral preparations) 1, 2
- Inadequate response to oral iron after adequate trial (hemoglobin increase <1 g/dL after 14 days) 1, 3
- Severe anemia with hemoglobin <10 g/dL requiring more rapid correction than oral iron can provide 1, 2
- Active inflammatory bowel disease where hepcidin activation impairs oral iron absorption 1, 2
- Chronic heart failure with iron deficiency (oral iron proven ineffective in this population) 1, 2
- Chronic kidney disease (non-dialysis dependent) 1, 4
- Heavy uterine bleeding or postpartum iron deficiency 1, 5
Diagnostic Criteria Before Treatment
Confirm iron deficiency using one of these criteria before initiating FCM:
- Serum ferritin <100 ng/mL, OR 2
- Serum ferritin 100-300 ng/mL with transferrin saturation <20% 2
- Alternative general population criteria: ferritin <30 ng/mL or transferrin saturation <20% 2
Do not administer if hemoglobin >15 g/dL 1, 2
Dosing Protocol
Standard dosing regimen:
- Maximum single dose: 1000 mg iron per administration 1, 2, 6
- Standard protocol: 15 mg/kg body weight up to maximum 750 mg per dose (US labeling) or 1000 mg (European practice) 1, 6
- Typical total dose: 1000-1500 mg restores iron stores to normal 1
Weight and hemoglobin-based dosing for heart failure patients:
- Hemoglobin <10 g/dL: 500 mg (<35 kg), 1500 mg (35-70 kg), 2000 mg (≥70 kg) 1
- Hemoglobin 10-14 g/dL: 500 mg (<35 kg), 1000 mg (35-70 kg), 1500 mg (≥70 kg) 1
- Hemoglobin 14-15 g/dL: 500 mg regardless of weight 1
If total calculated dose exceeds 1000 mg, administer in divided doses separated by at least 7 days 1, 6
Administration Procedure
Preparation and infusion:
- Dilute FCM in 100 mL normal saline before administration 1
- Infuse over 15-30 minutes (minimum 15 minutes) 1, 2, 6
- Alternative: undiluted slow IV bolus over 15 minutes for doses up to 1000 mg 1
Safety requirements:
- Ensure resuscitation facilities are immediately available due to potential anaphylaxis risk 2, 7
- Observe patients for adverse effects for at least 30 minutes following each IV injection 1, 2
- Confirm proper IV line placement to avoid extravasation and skin staining 1
Monitoring and Follow-Up
Immediate monitoring:
Laboratory evaluation timing:
- Do not check iron parameters within 4 weeks of administration as circulating iron interferes with assay leading to inaccurate results 1
- Obtain complete blood count and iron parameters (ferritin, transferrin saturation) 4-8 weeks after the last infusion 1
- Re-evaluate iron status at 3 months after initial treatment 1, 2
Expected response:
- Reticulocytosis occurs at 3-5 days post-administration 1
- Hemoglobin concentrations increase within 1-2 weeks of treatment 1
- Hemoglobin should increase by 1-2 g/dL within 4-8 weeks 1
- Mean hemoglobin increase of 8 g/L over 8 days following single dose 1
Clinical Efficacy Evidence
Superior to oral iron:
- FCM produces mean hemoglobin increase of 1.57 g/dL versus 0.80 g/dL with oral iron in patients with inadequate oral response 3
- In chronic kidney disease, 60.4% of FCM patients achieved hemoglobin increase ≥1 g/dL versus 34.7% with oral iron 4
Heart failure outcomes:
- AFFIRM-AHF trial showed 26% reduction in heart failure hospitalizations (RR 0.74; 95% CI 0.58-0.94) 1
- Significant improvements in NYHA functional class, 6-minute walk test (mean increase 18 meters vs -7 meters with placebo), and quality of life 1, 2, 6
- Benefits occur independent of anemia presence 1
Critical Safety Considerations
Absolute contraindications:
- Hypersensitivity to FCM or its excipients 1, 2
- Known serious hypersensitivity to other parenteral iron products 1, 2
- Anemia not attributed to iron deficiency 1, 2
- Evidence of iron overload 1
- Hemoglobin >15 g/dL 1, 2
Use with caution in:
- Acute or chronic infection (stop treatment in patients with bacteremia) 1, 2
- Known drug allergies, especially severe asthma, eczema, or atopic allergies 1, 2
- Immune or inflammatory conditions 1, 2
Hypophosphatemia risk:
- FCM causes treatment-emergent hypophosphatemia in 47-75% of patients (58% with FCM vs 4% with iron derisomaltose vs 1% with iron sucrose) 1
- Most cases are biochemically moderate (serum phosphate 0.32-0.64 mmol/L) and asymptomatic, resolving without intervention 1
- Avoid FCM in patients requiring repeat infusions within 3 months; use alternative formulations instead 1, 7
Anaphylaxis risk:
- True anaphylaxis is very rare (<0.1-1.0% frequency) 1
- Lower risk compared to iron dextran, with no reported cases of true anaphylaxis to date 1
- Complement activation-related pseudo-allergy (infusion reactions) can occur 1
Maintenance Therapy for Inflammatory Bowel Disease
Proactive maintenance approach:
- Assess serum ferritin every 2 months 2
- Administer 500 mg FCM when ferritin falls below 100 μg/L 2
- This prevents anemia recurrence (27% vs 40% becoming anemic, hazard ratio 0.62) 1
- Gastrointestinal symptoms and IBD flares are less frequent with FCM maintenance 1
Advantages Over Other IV Iron Formulations
Practical benefits:
- High single-dose capacity (1000 mg vs 200 mg for iron sucrose) with fewer clinic visits required (1-2 infusions vs 4-7 visits) 1
- Rapid administration (15-30 minutes vs 4-6 hours for low molecular weight iron-dextran) 1
- Lower anaphylaxis risk compared to iron dextran 1, 7
Cost-effectiveness:
- Despite higher acquisition cost (£217.50 per gram vs £70.80 for iron sucrose), overall cost savings occur due to fewer clinic visits 1
- Average annual healthcare costs reduced in anemic IBD patients (USD 19,113 vs USD 7,678) 1
Management of Allergic Reactions
If hypersensitivity reaction occurs:
- Administer standard anaphylaxis management including epinephrine, antihistamines, corticosteroids, and supportive care 7
Alternative IV iron formulations after FCM allergy:
- Iron sucrose: most studied preparation, 200 mg maximum per infusion over 10 minutes, rare severe adverse events 7
- Ferric derisomaltose: allows total dose infusion up to 1500 mg, FDA-labeled for single-dose administration 7
- Low molecular weight iron dextran: permits total dose infusion of 20 mg/kg over 6 hours, but carries 0.6-0.7% risk of serious reactions 7
Special Populations
Pregnancy:
- Avoid all IV iron formulations prior to 13 weeks gestation 7
- FCM effective and well-tolerated for postpartum iron deficiency 1, 5
Chronic kidney disease:
- For dialysis patients, iron sucrose may be preferred due to ease of administration through dialysis line 1
- For non-dialysis dependent CKD, FCM is superior to oral iron (mean hemoglobin increase 0.95 g/dL vs 0.50 g/dL at Day 42) 4
Post-transfusion timing:
- FCM can be administered immediately after packed red blood cell transfusion if clinically indicated 1
- Wait until post-transfusion hemoglobin is measured to ensure it remains ≤15 g/dL 1
- Confirm hemodynamic stability post-transfusion 1
- Delay if active bacteremia or ongoing infection present 1
Common Pitfalls to Avoid
- Do not recheck iron parameters within 4 weeks of FCM administration as ferritin levels increase markedly and cannot be used as accurate indicator 1
- Do not use FCM for repeat infusions within 3 months due to cumulative hypophosphatemia risk 1, 7
- Do not calculate total iron need based on ferritin or TSAT levels; use body weight and hemoglobin levels 1
- Question all patients about prior reactions to parenteral iron products before any IV iron administration 7