What intravenous (IV) iron repletion protocol should be used for an adult with iron‑deficiency anemia (low hemoglobin, low ferritin) who cannot tolerate oral iron or requires rapid repletion (e.g., chronic kidney disease (CKD), heart failure (HF), peri‑operative preparation, or persistent symptomatic anemia)?

IV Iron Repletion Protocol for Iron Deficiency Anemia

For adults with iron deficiency anemia requiring IV iron, administer ferric carboxymaltose 750 mg intravenously in two doses separated by at least 7 days (total cumulative dose 1,500 mg per course), or alternatively 15 mg/kg up to a maximum of 1,000 mg as a single dose for patients ≥50 kg. 1

Indications for IV Iron Over Oral Iron

IV iron should be used as first-line therapy in the following clinical scenarios:

• Patients on hemodialysis or receiving erythropoiesis-stimulating agents (ESAs) 2, 3
• Oral iron intolerance, ineffectiveness, or malabsorption 4, 5, 1
• Severe anemia requiring rapid repletion 4
• Chronic kidney disease (CKD) patients, particularly those on dialysis 2, 3
• Heart failure patients with iron deficiency (even without anemia) 4, 1, 6
• Patients with chronic inflammatory conditions where oral iron absorption is impaired 5

Specific Dosing Protocols by Formulation

Ferric Carboxymaltose (Injectafer) - Preferred for Rapid Repletion

For patients ≥50 kg:

• Standard protocol: 750 mg IV × 2 doses separated by ≥7 days (total 1,500 mg per course) 1
• Alternative single-dose protocol: 15 mg/kg up to maximum 1,000 mg IV as single dose 1

For patients <50 kg:

• 15 mg/kg IV × 2 doses separated by ≥7 days 1

For heart failure patients with iron deficiency:

• Dosing varies based on body weight and hemoglobin (see FDA label Table 1) 1
• Treatment improves exercise capacity in NYHA class II/III heart failure 4, 1

Alternative IV Iron Formulations

Iron sucrose:

• Maximum 200 mg per dose, given as slow IV infusion 4
• Requires multiple visits (up to 5 doses for 1,000 mg total) 6
• No test dose required 4
• Approved for CKD patients 4

Ferric derisomaltose:

• Single 1,000 mg infusion 6
• Associated with fewer cardiovascular adverse events compared to iron sucrose in CKD patients 6

Low molecular weight iron dextran (Infed):

• Can administer >1,000 mg by infusion 4
• Requires mandatory test dose due to anaphylaxis risk (boxed warning) 4
• Lower cost but higher risk profile 4

Iron gluconate:

• Maximum 125 mg per dose 4
• No test dose required 4

Ferumoxytol:

• 510 mg × 2 doses 4
• Must be given as slow infusion (not rapid) due to postmarketing adverse events 4

Calculating Total Iron Deficit

Use the Ganzoni formula to calculate total iron deficit, or provide an empiric total dose of 1,000 mg with interval reassessment. 4

Ganzoni formula:

• Total iron deficit (mg) = Body weight (kg) × (Target Hb - Actual Hb) (g/dL) × 2.4 + 500 mg (for iron stores)

Monitoring Protocol

Assess response at 1 month after IV iron administration:

• Adequate response: Hemoglobin rise ≥1.0 g/dL (≥10 g/L) 4, 5
• Normalization of ferritin and transferrin saturation 4

For CKD patients, monitor using:

• Red blood cell markers (percentage hypochromic RBCs >6%, reticulocyte hemoglobin content) - most cost-effective 2
• If RBC markers unavailable: transferrin saturation <20% AND ferritin <100 ng/mL (non-dialysis) or <200 ng/mL (hemodialysis) indicates iron deficiency 2, 3

Monitor serum phosphate levels in patients at risk for hypophosphatemia who require repeat courses 1

Maintenance Therapy

Regularly-scheduled iron infusions should be expected unless chronic bleeding is halted through systemic therapies or procedural interventions. 4

For CKD patients on hemodialysis:

• High-dose low-frequency administration is recommended for most adults 2
• Low-dose high-frequency administration may be more appropriate for children and some adults receiving in-center hemodialysis 2

Repeat courses when iron deficiency anemia or iron deficiency in heart failure recurs. 1

Safety Monitoring

Observe patients for hypersensitivity reactions during and for at least 30 minutes after administration until clinically stable. 1

Monitor for:

• Hypertension - most common adverse reaction (>2% incidence) 1
• Hypophosphatemia - particularly common in pediatric patients (≥4% incidence) 1
• Injection site reactions, flushing, nausea, dizziness 1

Contraindications:

• Known hypersensitivity to ferric carboxymaltose or any inactive components 1

Special Clinical Scenarios

Heart Failure Patients

• IV iron improves exercise capacity, NYHA class, quality of life, and fatigue scores even in non-anemic patients with iron deficiency 4
• Benefits sustained to 52 weeks with ferric carboxymaltose 4
• Associated with reduced hospitalization rates for worsening heart failure 4

CKD Patients

• Absolute iron deficiency: TSAT ≤20% and ferritin ≤100 ng/mL (non-dialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis) 3
• Functional iron deficiency: TSAT ≤20% with elevated ferritin (due to increased hepcidin) 3
• IV iron preferred over oral for all dialysis patients and those receiving ESAs 2, 3

Pregnancy

• Risk of hypersensitivity reactions which may have serious consequences for the fetus 1
• Careful risk-benefit assessment required 1

Common Pitfalls to Avoid

• Do not use high molecular weight iron dextran (Dexferrum) - removed from market due to high adverse reaction rates 4
• Do not omit test dose when using low molecular weight iron dextran - anaphylaxis risk requires mandatory testing 4
• Do not use rapid infusion rates for ferumoxytol - associated with increased adverse events 4
• Do not withhold IV iron during inflammation, but withhold during acute infection 7
• Do not rely on ferritin or transferrin saturation alone in CKD patients - use RBC markers when available 2
• Do not assume oral iron will work in CKD patients on ESAs or dialysis - IV iron is superior 2, 3