What are the indications for intravenous (IV) iron therapy in patients with iron deficiency anemia, including those with chronic kidney disease, cancer, or heavy menstrual bleeding?

Indications for Intravenous Iron Therapy

Intravenous iron is indicated for iron deficiency anemia when oral iron is ineffective, not tolerated, or contraindicated, and is specifically approved for chronic kidney disease patients, with strong evidence supporting use in cancer-related anemia, heart failure, inflammatory bowel disease, pregnancy (second/third trimester), ongoing blood loss, and malabsorption conditions. 1, 2

Primary FDA-Approved Indication

• IV iron sucrose (and other IV iron formulations) are FDA-approved for treatment of iron deficiency anemia in patients with chronic kidney disease 1

Clinical Indications Based on Iron Deficiency Type

Absolute Iron Deficiency

• Use IV iron monotherapy when ferritin <30 ng/mL and transferrin saturation (TSAT) <15% in cancer patients 3
• For CKD patients, absolute iron deficiency is defined as TSAT ≤20% with ferritin ≤100 ng/mL (predialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis) 4
• IV iron is preferred over oral iron for all dialysis patients (CKD stage 5D) 4

Functional Iron Deficiency

• In cancer patients with chemotherapy-induced anemia and functional iron deficiency (ferritin ≤800 ng/mL, TSAT <20%), use IV iron combined with erythropoiesis-stimulating agents (ESAs) 3
• Functional iron deficiency occurs when adequate iron stores exist but insufficient iron is available for erythropoiesis, typically due to elevated hepcidin from inflammation 4

Condition-Specific Indications

Cancer-Related Anemia

• IV iron monotherapy for absolute iron deficiency (ferritin <30 ng/mL, TSAT <15%) 3
• IV iron plus ESA for functional iron deficiency during chemotherapy 3
• IV iron monotherapy reduced transfusion rates (9% vs 20%, P=0.005) in one major trial 3
• Do NOT administer IV iron during active infection or neutropenia due to risk of bacterial growth 3
• Consider avoiding IV iron on same day as anthracyclines due to theoretical cardiotoxicity risk 3

Chronic Kidney Disease

• IV iron is the preferred route for all hemodialysis patients 4
• Either IV or oral iron can be used for non-dialysis CKD (stages 3-5), though IV is often more effective 4
• Screen all CKD patients for anemia during initial evaluation 4

Pregnancy

• IV iron is indicated during second and third trimesters when oral iron fails or is not tolerated 2
• Up to 84% of pregnant women develop iron deficiency during third trimester in high-income countries 2

Heavy Menstrual Bleeding

• IV iron is appropriate when oral iron is ineffective or not tolerated in reproductive-age women with iron deficiency 5, 2
• Approximately 38% of nonpregnant reproductive-age women have iron deficiency without anemia, and 13% have iron-deficiency anemia 2

Inflammatory Bowel Disease

• IV iron is preferred over oral iron due to chronic inflammation causing functional iron deficiency 2
• Iron deficiency affects 13-90% of IBD patients 2

Heart Failure

• IV iron is indicated for symptomatic heart failure patients with iron deficiency (37-61% prevalence) 2
• Improves symptoms and quality of life even in absence of anemia 2

Hepatic Insufficiency

• Attempt oral iron first, even with portal hypertensive gastropathy 6
• IV iron is indicated when there is ongoing bleeding with inadequate response to oral iron 6
• No specific contraindications exist based solely on hepatic insufficiency 6
• Use ferritin <45 ng/mL as threshold in anemic patients, adjusted for liver inflammation 6

Oral Iron Failure Criteria

IV iron should be used when oral iron has failed, defined as: 5, 2, 7

• Intolerance to oral iron (gastrointestinal side effects)
• Inadequate hemoglobin response after adequate trial
• Malabsorption conditions (celiac disease, atrophic gastritis, post-bariatric surgery)
• Ongoing blood loss exceeding oral iron replacement capacity
• Chronic inflammatory conditions where oral iron is ineffective

Practical Administration Guidelines

Formulation Selection

• Choose high-dose formulations allowing complete repletion in 1-2 infusions (ferric carboxymaltose or iron isomaltoside) 6
• Avoid high-molecular-weight iron dextran (Dexferrum) due to increased anaphylaxis risk 3
• Low-molecular-weight iron dextran (INFeD) is acceptable if used 3
• Test doses required for iron dextran; strongly recommended for ferric gluconate or iron sucrose in patients with drug allergies 3

Safety Monitoring

• True anaphylaxis is extremely rare; most reactions are complement activation-related pseudo-allergy (infusion reactions) 6
• Manage infusion reactions by temporarily stopping and restarting at slower rate 6
• Avoid diphenhydramine for infusion reactions as side effects can mimic worsening reaction 6
• Common adverse events include hypotension, nausea, vomiting, diarrhea, pain, hypertension, dyspnea, pruritus, headache, dizziness 3

Response Assessment

• Check hemoglobin within 2 weeks; expect approximately 1 g/dL increase if responding appropriately 6
• In clinical trials, 81.1% of patients achieved ≥2.0 g/dL hemoglobin increase at week 5 with IV ferumoxytol versus 5.5% with placebo 7
• Mean hemoglobin increase was 2.7 g/dL with IV iron versus 0.1 g/dL with placebo at week 5 7

Critical Contraindications

• Active infection (theoretical risk of promoting bacterial growth) 3
• Neutropenia in cancer patients 3
• Known hypersensitivity to specific IV iron formulation
• Iron overload (ferritin >800 ng/mL and TSAT >50% in cancer patients) 3

Common Pitfalls to Avoid

• Do not withhold IV iron based solely on elevated ferritin in inflammatory conditions—use TSAT to guide decisions 3, 4
• Do not assume oral iron will be ineffective without attempting it first, except in clear contraindications 6
• In cancer patients, the Steensma trial showed no benefit when baseline TSAT was 22.5%, suggesting IV iron may not help when TSAT is already adequate 3
• Do not use IV iron as monotherapy for functional iron deficiency in cancer patients receiving chemotherapy—combine with ESA 3