What is the recommended treatment regimen for intravenous (IV) iron infusion in patients with heart failure and iron deficiency?

IV Iron Infusion in Heart Failure

Intravenous ferric carboxymaltose (FCM) should be administered to symptomatic patients with heart failure with reduced ejection fraction (LVEF <40%) who have iron deficiency, as this improves functional capacity, quality of life, and reduces heart failure hospitalizations. 1

Patient Selection Criteria

Who qualifies for IV iron therapy:

• Symptomatic chronic heart failure with LVEF ≤45% (Class IIa recommendation, Level A evidence) 1
• Iron deficiency defined as:
  • Serum ferritin <100 μg/L, OR
  • Serum ferritin 100-299 μg/L when transferrin saturation (TSAT) <20% 1

Important caveat: While guidelines use ferritin <100 μg/L as a cutoff, emerging evidence suggests patients with TSAT <20% (most of whom are also anemic) are more likely to benefit from IV iron therapy 2. The current ferritin-based definition has significant limitations in identifying responders 2.

Limited or no evidence exists for:

• Heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%) 1
• Heart failure with mid-range ejection fraction (HFmrEF, LVEF 40-49%) 1

Dosing Regimen

For Iron Deficiency Anemia in Heart Failure

Standard dosing (body weight ≥50 kg):

• FCM 750 mg IV in two doses separated by at least 7 days
• Total cumulative dose: 1,500 mg iron per course 3

Alternative single-dose regimen:

• FCM 15 mg/kg body weight (maximum 1,000 mg) as a single dose 3

For patients <50 kg:

• FCM 15 mg/kg body weight in two doses separated by at least 7 days 3

For Iron Deficiency in Heart Failure (Without Anemia Focus)

Weight-based and hemoglobin-stratified dosing: 3

Patients <70 kg:

• Hb <10 g/dL: 1,000 mg on Day 1, then 500 mg at Week 6
• Hb 10-14 g/dL: 1,000 mg on Day 1, no additional dose at Week 6
• Hb >14 to <15 g/dL: 500 mg on Day 1, no additional dose at Week 6

Patients ≥70 kg:

• Hb <10 g/dL: 1,000 mg on Day 1, then 1,000 mg at Week 6
• Hb 10-14 g/dL: 1,000 mg on Day 1, then 500 mg at Week 6
• Hb >14 to <15 g/dL: 500 mg on Day 1, no additional dose at Week 6

Maintenance dosing:

• Administer 500 mg at 12,24, and 36 weeks if serum ferritin <100 ng/mL OR ferritin 100-300 ng/mL with TSAT <20% 3

Maximum weekly dose: 1,000 mg iron (20 mL FCM) per week 1

Administration Technique

FCM can be given as either:

Undiluted Slow IV Push

• Rate: 100 mg/min (approximately 2 mL/min) 1
• For 1,000 mg dose: administer over 15 minutes 1, 3

IV Infusion (requires dilution)

• 500 mg dose: Dilute 10 mL FCM in maximum 100 mL sterile 0.9% sodium chloride; infuse over minimum 6 minutes 1
• 1,000 mg dose: Dilute 20 mL FCM in maximum 250 mL sterile 0.9% sodium chloride; infuse over minimum 15 minutes 1, 3

Critical dilution requirement: Do not over-dilute; concentration must not be less than 2 mg iron/mL to maintain drug stability 1, 3

Post-administration monitoring: Observe patients for adverse effects for at least 30 minutes following each injection 1, 4, 3

Monitoring Strategy

Initial reassessment:

• Re-evaluate iron status at 3 months after correction dose 1
• Provide further iron repletion as needed 1

Avoid early testing:

• Do not check iron status within 4 weeks of IV iron administration, as ferritin levels increase markedly and cannot accurately reflect iron stores during this period 1

Routine follow-up:

• Re-evaluate iron parameters (ferritin and TSAT) 1-2 times per year in patients with known heart failure 1
• Check iron status when symptoms persist despite optimal heart failure medications 1
• Reassess if hemoglobin levels decrease 1

If no response or hemoglobin decreases:

• Investigate for occult blood loss and other underlying causes 1

Absolute Contraindications

Do not administer FCM in patients with: 1, 4, 3

• Hypersensitivity to FCM or its excipients
• Known serious hypersensitivity to other parenteral iron products
• Anemia not attributed to iron deficiency (e.g., other microcytic anemias)
• Evidence of iron overload or disturbances in iron utilization
• Hemoglobin levels >15 g/dL (efficacy and safety not established) 1, 4

High-Risk Situations Requiring Caution

Use with extreme caution or avoid in: 1, 4

• Acute or chronic infection: Use clinical judgment; stop FCM immediately in patients with ongoing bacteremia
• History of severe allergies: Patients with severe asthma, eczema, or other atopic allergies have increased hypersensitivity risk
• Immune/inflammatory conditions: Systemic lupus erythematosus, rheumatoid arthritis patients have increased hypersensitivity risk
• Known drug allergies: Increased risk of hypersensitivity reactions

Pediatric limitation: FCM not studied in children under 14 years of age 4

Safety Profile and Adverse Events

Common side effects (≥1% to <10%): 1

• Dizziness, headache
• Hypertension
• Hypophosphatemia
• Injection-site reactions
• Nausea

Serious hypersensitivity reactions:

• Anaphylactic/anaphylactoid reactions occur in 0.1% of patients 3
• Other serious hypersensitivity reactions (pruritus, rash, urticaria, wheezing, hypotension) in 1.5% 3
• If anaphylaxis occurs: Immediately discontinue infusion and administer epinephrine 4

Extravasation risk:

• Brown skin discoloration may be long-lasting 3
• Monitor for extravasation; discontinue immediately if occurs 3
• Ensure proper IV line placement and care 1

Clinical Benefits

Proven improvements in HFrEF patients (LVEF ≤45%): 1

• Functional capacity and exercise tolerance
• Heart failure symptoms
• Health-related quality of life
• Potential reduction in heart failure-related hospitalizations

Meta-analysis findings: IV iron therapy significantly reduces composite outcomes (RR 0.84) and heart failure hospitalizations (RR 0.74) compared to standard care 5

Mortality data: Clinical trials were not designed or powered to evaluate survival effects; no demonstrated mortality benefit to date 1, 5

Oral Iron: Not Recommended

Oral iron therapy is not effective for iron deficiency in heart failure: 1

• The IRONOUT HF trial showed oral iron minimally replenished iron stores and did not improve exercise capacity or symptoms
• Gastrointestinal side effects occur in up to 60% of patients
• Poor absorption requires >6 months for iron repletion
• No randomized trials comparing IV versus oral iron in heart failure exist

Administration Setting

FCM can be administered in: 1

• Hospital setting
• Community setting

Requirements: Staff must be trained and equipped to monitor for and manage hypersensitivity reactions 1

Repeat Treatment Considerations

When to repeat: 3

• May repeat if iron deficiency anemia or iron deficiency in heart failure recurs
• Check serum phosphate levels in patients at risk for low phosphate who require repeat treatment
• Check phosphate for any patient receiving repeat treatment within 3 months
• Treat hypophosphatemia as medically indicated