What is the recommended dose of ferric carboxymaltose (intravenous iron replacement therapy) for treating iron deficiency anemia?

Ferric Carboxymaltose Dosing

For iron deficiency anemia in adults weighing ≥50 kg, administer ferric carboxymaltose 750 mg intravenously on two occasions separated by at least 7 days for a total cumulative dose of 1,500 mg per course, or alternatively, a single dose of 15 mg/kg (maximum 1,000 mg) can be given. 1

Standard Dosing for Iron Deficiency Anemia

Weight-Based Dosing

• Patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg per course) 1
• Alternative for patients ≥50 kg: Single dose of 15 mg/kg up to maximum 1,000 mg 1
• Patients <50 kg: 15 mg/kg IV in two doses separated by at least 7 days 1

Regional Variations

• United States: Distributed as 750 mg vials with labeling for two doses 1 week apart 2, 3
• Europe and Asia: Routinely administered as 1,000 mg single infusion 2, 3
• Perioperative setting: 15 mg/kg (maximum 1,000 mg) as single dose over 15 minutes produces mean hemoglobin increase of 8 g/L over 8 days 2

Heart Failure with Iron Deficiency Dosing

For patients with heart failure and iron deficiency (ferritin <100 μg/L or ferritin 100-299 μg/L with transferrin saturation <20%), dosing is stratified by weight and hemoglobin level. 1, 4

Initial Dosing Algorithm (Table)

Weight	Hemoglobin <10 g/dL	Hemoglobin 10-14 g/dL	Hemoglobin >14 to <15 g/dL
<70 kg	Day 1: 1,000 mg Week 6: 500 mg	Day 1: 1,000 mg Week 6: No dose	Day 1: 500 mg Week 6: No dose
≥70 kg	Day 1: 1,000 mg Week 6: 1,000 mg	Day 1: 1,000 mg Week 6: 500 mg	Day 1: 500 mg Week 6: No dose

1

Maintenance Dosing for Heart Failure

• Administer 500 mg at 12,24, and 36 weeks if serum ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 1
• No data available to guide dosing beyond 36 weeks or with hemoglobin ≥15 g/dL 1
• Do not administer if hemoglobin >15 g/dL 3

Administration Technique

Preparation

• Dilute in 100 mL of normal saline (0.9% sodium chloride) 2, 3, 1
• Do not dilute to concentrations less than 2 mg iron/mL to maintain stability 1
• Solution is stable for 72 hours at room temperature when diluted to 2-4 mg iron/mL 1

Infusion Methods

• Standard infusion: Administer over 15-30 minutes 2, 3
• Slow IV push (500-750 mg): Approximately 100 mg (2 mL) per minute 1
• Slow IV push (1,000 mg): Administer over 15 minutes 1
• Rapid undiluted bolus: Up to 1,000 mg can be given as rapid bolus injection (well tolerated in Phase II study, though not standard FDA-labeled administration) 5

Monitoring During Administration

• Observe patients for adverse effects for at least 30 minutes following each IV injection 3
• Monitor for extravasation; if occurs, discontinue administration at that site (brown discoloration may be long-lasting) 1
• Have resuscitation facilities available 2

Laboratory Monitoring and Expected Response

Timing of Laboratory Assessment

• Do not check iron parameters within 4 weeks of administration as circulating iron interferes with assays leading to inaccurate results 3
• Check CBC and iron parameters (ferritin, transferrin saturation) 4-8 weeks after last infusion 2, 3
• For heart failure patients, re-evaluate iron status at 3 months after initial treatment 4

Expected Hemoglobin Response

• Hemoglobin should increase within 1-2 weeks of treatment 3
• Expected increase of 1-2 g/dL within 4-8 weeks 3
• Reticulocytosis occurs at 3-5 days after administration 2
• Mean hemoglobin increase of 8 g/L over 8 days with single 15 mg/kg dose 2

Expected Iron Parameter Changes

• Mean ferritin increase of 264 ng/mL (perioperative patients) and 432 ng/mL (CKD patients) 1, 6
• Mean transferrin saturation increase of 13-20% 1, 6

Repeat Dosing Considerations

When to Repeat Treatment

• Treatment may be repeated if iron deficiency anemia or iron deficiency in heart failure recurs 1
• Frequency depends on underlying etiology: single dose sufficient if cause eliminated; multiple administrations necessary for ongoing losses (heavy menstrual bleeding, inflammatory bowel disease) or malabsorption 2

Critical Precaution for Repeat Dosing

• Check serum phosphate levels in patients requiring repeat course or any patient receiving repeat course within 3 months 1
• Ferric carboxymaltose is associated with treatment-emergent hypophosphatemia and should be avoided in patients requiring frequent repeat infusions 2, 3
• Hypophosphatemia rates are 58% with ferric carboxymaltose versus 4% with iron derisomaltose and 1% with iron sucrose 3
• Most hypophosphatemia is biochemically moderate (0.32-0.64 mmol/L) and asymptomatic, resolving without intervention 3

Contraindications and Cautions

Absolute Contraindications

• Hypersensitivity to ferric carboxymaltose or its excipients 3, 4, 1
• Known serious hypersensitivity to other parenteral iron products 3, 4, 1
• Anemia not attributed to iron deficiency 3, 4, 1
• Evidence of iron overload 3, 4, 1

Use with Caution

• Acute or chronic infection (stop treatment in patients with bacteremia) 3, 4
• Known drug allergies, especially history of severe asthma, eczema, or atopic allergies 3, 4
• Immune or inflammatory conditions 4

Safety Profile

• Serious adverse reaction rate: 38 incidents per million episodes of administration 2
• Acute reactions mediated via complement activation due to nanoparticles rather than IgE-mediated response 2
• Treatment-related adverse events significantly fewer than oral iron (2.7% vs 26.2%) 6
• No anaphylaxis reported in initial trials 2

Clinical Efficacy Context

Advantages Over Oral Iron

• More effective than oral iron at restoring hemoglobin concentrations in both iron deficiency anemia and anemia of chronic disease 2
• Oral iron ineffective in inflammatory conditions due to hepcidin activation blocking iron absorption 2
• Oral iron shown ineffective in heart failure patients with iron deficiency (IRONOUT HF trial) 4

Cardiovascular Benefits

• First IV iron formulation associated with fewer cardiovascular events and hospitalizations in heart failure patients 2, 3
• Significantly improves exercise capacity (6-minute walk test), NYHA functional class, quality of life measures, and Patient Global Assessment scores 4
• May reduce heart failure hospitalizations 4