When should oral iron supplementation versus intravenous (IV) iron supplementation be used in patients with iron deficiency anemia, particularly those with chronic kidney disease (CKD), inflammatory bowel disease (IBD), or cancer?

When to Use Oral vs Intravenous Iron Supplementation

Oral iron (ferrous sulfate 200 mg once daily) is first-line treatment for patients with mild anemia (Hb >10 g/dL), clinically inactive disease, and no prior oral iron intolerance, while intravenous iron should be used as first-line therapy for patients with active inflammatory conditions, hemoglobin <10 g/dL, previous oral iron intolerance, or malabsorption conditions. 1

Indications for Oral Iron as First-Line Treatment

Use oral iron when ALL of the following criteria are met:

• Mild anemia (Hb 11.0-11.9 g/dL in non-pregnant women; 11.0-12.9 g/dL in men) 1
• Clinically inactive disease (no active inflammation) 1
• No previous intolerance to oral iron preparations 1
• No malabsorption conditions affecting iron absorption 2

Oral Iron Dosing Protocol

• Ferrous sulfate 200 mg (65 mg elemental iron) once daily is the preferred formulation due to effectiveness and low cost 2
• Once-daily dosing is superior to multiple daily doses—it improves tolerance while maintaining equal or better absorption due to hepcidin regulation 2
• Add vitamin C 500 mg with each iron dose to enhance absorption, especially when transferrin saturation is low 2
• Continue for 3 months after hemoglobin normalizes to fully replenish iron stores 2
• Alternative formulations (ferrous gluconate, ferrous fumarate) are equally effective if ferrous sulfate is not tolerated 2

Indications for Intravenous Iron as First-Line Treatment

Use IV iron as first-line when ANY of the following are present:

Active Inflammatory Conditions

• Active inflammatory bowel disease (IBD) with Hb <10 g/dL 1
• Clinically active IBD regardless of hemoglobin level 1
• Inflammation-induced hepcidin elevation severely impairs oral iron absorption, making oral therapy ineffective 1

Severe Anemia

• Hemoglobin <10 g/dL (100 g/L) in any patient population 1
• This threshold indicates need for more rapid correction than oral iron can provide 1

Previous Oral Iron Intolerance

• Intolerance to at least two different oral iron preparations (e.g., ferrous sulfate, ferrous gluconate, ferrous fumarate) 1, 2
• Common side effects include constipation, diarrhea, nausea, and abdominal discomfort 3

Malabsorption Conditions

• Post-bariatric surgery patients due to disrupted duodenal absorption mechanisms 2
• Celiac disease with inadequate response to oral iron despite gluten-free diet adherence 2
• Active IBD where luminal iron may exacerbate disease activity 1

Need for Erythropoiesis-Stimulating Agents (ESAs)

• Patients requiring ESA therapy should receive IV iron to optimize response 1

Chronic Kidney Disease

• Hemodialysis patients (CKD stage 5D): IV iron is preferred 4
• Non-dialysis CKD (stages 3-5): Either IV or oral iron acceptable, but IV preferred for functional iron deficiency 4
• Functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%) often requires IV iron 4

Preferred IV Iron Formulations

Choose IV iron preparations that replace iron deficits in 1-2 infusions rather than multiple infusions to minimize risk and improve convenience 2

Recommended Formulations:

• Ferric carboxymaltose: 500-1000 mg single doses, delivered within 15 minutes 1
• Iron isomaltoside 1000: Large single-dose capability 1
• Iron sucrose: Requires multiple visits (200-300 mg per infusion) 1, 5

Avoid:

• Iron dextran preparations carry higher risk of anaphylaxis and require test doses 1

IV Iron Dosing Based on Hemoglobin and Body Weight

For IBD patients 1:

Hemoglobin (g/dL)	Body Weight <70 kg	Body Weight ≥70 kg
10-12 (women) / 10-13 (men)	1000 mg	1500 mg
7-10	1500 mg	2000 mg

Expected Response and Monitoring

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment with either oral or IV iron 1, 2
• Check hemoglobin at 4 weeks: Failure to rise indicates poor compliance, continued blood loss, or malabsorption 2
• Monitor every 3 months for the first year, then again after another year 2

Special Population Considerations

Inflammatory Bowel Disease

• IV iron is more effective (odds ratio 1.57 for achieving 2.0 g/dL hemoglobin increase) and better tolerated than oral iron 1
• Oral iron may worsen disease activity in active IBD through effects on intestinal microbiota and mucosal inflammation 1
• Oral iron acceptable only if: disease is clinically inactive, anemia is mild (Hb >10 g/dL), and no prior intolerance 1
• Limit oral iron to ≤100 mg elemental iron daily in IBD patients to minimize potential inflammatory effects 1

Chronic Kidney Disease

• Dialysis patients: IV iron is preferred route 4
• Non-dialysis CKD: Either IV or oral acceptable, but IV preferred for functional iron deficiency 4
• Different diagnostic criteria: Absolute iron deficiency defined as TSAT ≤20% with ferritin ≤100 ng/mL (predialysis/peritoneal dialysis) or ≤200 ng/mL (hemodialysis) 4

Pregnant Women

• Oral iron is first-line: 30 mg/day for prevention, 60-120 mg/day for treatment 2
• IV iron indicated during second and third trimesters if oral iron fails or is not tolerated 2

Critical Pitfalls to Avoid

• Do NOT prescribe multiple daily doses of oral iron—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 2
• Do NOT continue oral iron in active IBD with Hb <10 g/dL—this is ineffective and potentially harmful 1
• Do NOT stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 2
• Do NOT overlook vitamin C supplementation when oral iron response is suboptimal 2
• Do NOT use iron dextran as first-line IV formulation due to higher anaphylaxis risk 1
• Do NOT delay IV iron in patients with clear indications (active inflammation, severe anemia, malabsorption) 1

Safety Considerations for IV Iron

• True anaphylaxis is very rare (0.6-0.7% with iron dextran, even lower with newer formulations) 2
• Most reactions are infusion reactions (complement activation-related pseudo-allergy) that respond to slowing the infusion rate 2, 5
• Resuscitation facilities must be available when administering any IV iron formulation 1, 5
• Monitor for hypophosphatemia with ferric carboxymaltose 6
• Upper limits for therapy: Transferrin saturation >50% and ferritin >800 μg/L should guide cessation to avoid iron overload 1

Algorithm for Route Selection

1. Assess disease activity and inflammation: If active IBD or inflammatory condition → IV iron 1
2. Check hemoglobin level: If Hb <10 g/dL → IV iron 1
3. Evaluate prior oral iron trials: If intolerant to ≥2 formulations → IV iron 2
4. Assess absorption capacity: If post-bariatric surgery, celiac disease with ongoing exposure, or other malabsorption → IV iron 2
5. If none of above apply AND disease is inactive with mild anemia → Oral iron 1