What is the recommended iron supplementation regimen for confirmed iron deficiency anemia, including dosing, administration, and monitoring?

Iron Supplementation for Confirmed Iron Deficiency Anemia

Start oral ferrous sulfate 200 mg (≈65 mg elemental iron) once daily immediately upon diagnosis, add vitamin C 500 mg with each dose, and continue for 3 months after hemoglobin normalizes—typically 6–7 months total. 1

First-Line Oral Iron Regimen

• Ferrous sulfate 200 mg once daily is the preferred first-line treatment because it provides the most cost-effective option with efficacy equal to all other oral iron formulations. 1, 2
• Once-daily dosing is superior to multiple daily doses because hepcidin remains elevated for approximately 48 hours after iron intake, blocking further absorption and increasing gastrointestinal side effects without improving hemoglobin response. 1, 2
• Take the dose on an empty stomach for optimal absorption; if gastrointestinal intolerance occurs, taking with food is acceptable. 1
• Add vitamin C 500 mg with each iron dose to markedly enhance absorption, especially critical when transferrin saturation is severely low. 1, 2
• Avoid tea and coffee within 1 hour of taking iron, as these beverages strongly inhibit absorption. 1
• Alternative formulations (ferrous fumarate ≈106 mg elemental iron or ferrous gluconate ≈38 mg elemental iron) are equally effective if ferrous sulfate is not tolerated, though typically more expensive. 1, 2

Expected Response and Monitoring Protocol

• Check hemoglobin at 4 weeks—expect a rise of approximately 2 g/dL (≥10 g/L). 1, 2
• Failure to achieve ≥10 g/L rise by 2 weeks predicts overall treatment failure with 90.1% sensitivity and 79.3% specificity. 1
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores; total treatment duration is typically 6–7 months. 1, 2
• Monitor hemoglobin and red-cell indices every 3 months during the first year, then again after the second year. 1, 2
• Do not check iron parameters within 4 weeks of starting therapy, as circulating iron interferes with assays leading to spurious results. 2

Absolute Indications for Switching to Intravenous Iron

Switch to IV iron when oral therapy fails or is contraindicated—do not persist with ineffective oral iron beyond 4 weeks. 1

• Intolerance to at least two different oral iron preparations (e.g., ferrous sulfate and ferrous fumarate or gluconate). 1, 2
• Ferritin fails to improve after 4 weeks of compliant oral therapy. 1, 2
• Hemoglobin fails to rise by ≥1 g/dL after 4 weeks despite adherence. 1
• Active inflammatory bowel disease with hemoglobin <10 g/dL—IV iron is first-line because inflammation-driven hepcidin markedly impairs oral absorption. 1, 2
• Post-bariatric surgery patients due to disrupted duodenal iron absorption mechanisms. 1, 2
• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence. 1, 2
• Chronic heart failure with iron deficiency (ferritin <100 ng/mL or 100–300 ng/mL with transferrin saturation <20%), where IV iron improves symptoms and quality of life. 1, 2
• Ongoing gastrointestinal blood loss that exceeds oral replacement capacity. 1
• Pregnancy during second and third trimesters when oral iron fails to correct anemia. 1, 3

Preferred Intravenous Iron Formulations

Choose IV iron products that can replenish the iron deficit in 1–2 infusions to minimize infusion-related risk and improve convenience. 1, 2

• Ferric carboxymaltose: 750–1000 mg administered over 15 minutes; two doses given ≥7 days apart provide a total of 1500 mg. 1, 2, 4
• Ferric derisomaltose (iron dextran): 1000 mg can be delivered as a single infusion; this is the only formulation with FDA approval for total dose infusion. 2, 4
• Avoid iron dextran as first-line because it carries a higher risk of anaphylaxis (≈0.6–0.7%); true anaphylaxis with any IV iron is rare. 1, 2
• Most infusion reactions are complement-activation pseudo-allergies (CARPA) that respond to slowing the infusion rate rather than true anaphylaxis requiring epinephrine. 1, 2
• All IV iron administrations must occur in a setting equipped with resuscitation facilities, with monitoring for at least 30 minutes after completion. 1, 2, 4

Diagnostic Workup for Underlying Cause

Do not delay iron therapy while awaiting diagnostic workup, unless colonoscopy is scheduled within days—iron can impair endoscopic visualization. 1, 2

• All adult men and postmenopausal women require bidirectional endoscopy (upper endoscopy + colonoscopy) to exclude gastrointestinal malignancy. 1, 2, 5
• Premenopausal women: Assess menstrual blood loss first—menorrhagia, pregnancy, and breastfeeding account for iron deficiency in 5–10% of menstruating women. 1, 6, 3
• Screen for celiac disease with tissue transglutaminase IgA antibodies and total IgA measurement—celiac disease is present in 3–5% of iron-deficiency cases. 1, 5
• Test for Helicobacter pylori using stool antigen or urea-breath test and eradicate if positive. 1
• Reserve endoscopy in premenopausal women for those ≥50 years, with gastrointestinal symptoms, alarm features, or strong family history of colorectal cancer. 1

Special Population Considerations

Inflammatory Bowel Disease

• IV iron is first-line when hemoglobin <10 g/dL with active inflammation, as oral iron is poorly absorbed and may worsen inflammation. 1, 2
• For mild anemia (hemoglobin >10 g/dL) with quiescent disease, oral iron may be used if disease is truly inactive. 1
• Elemental iron doses should not exceed 100 mg per day in IBD patients, as higher doses may trigger intestinal inflammation. 1
• Re-initiate iron therapy when ferritin drops below 100 ng/mL or hemoglobin falls below 12 g/dL (women) or 13 g/dL (men). 1

Chronic Kidney Disease

• IV iron is preferred for hemodialysis patients; either IV or oral iron for non-dialysis CKD stages 3–5. 1
• Functional iron deficiency is defined by ferritin 100–300 ng/mL with transferrin saturation <20%. 1

Pregnancy

• Start oral low-dose iron 30 mg/day at first prenatal visit for prevention. 1, 2
• Treat anemia with 60–120 mg/day elemental iron; IV iron is safe and effective during second and third trimesters when oral iron fails. 1, 2, 3
• Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation. 1, 2

Critically Ill Patients

• In anemic critically ill patients with iron deficiency confirmed by low hepcidin levels, administer 1 g of IV iron as a single dose using carbohydrate-bound formulations. 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. 1, 2
• Do not discontinue iron therapy when hemoglobin normalizes—continue for an additional 3 months to restore iron stores. 1, 2
• Do not persist with oral iron beyond 4 weeks without a hemoglobin rise—reassess for malabsorption, ongoing loss, or need for IV iron. 1, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal. 1, 2
• Do not fail to identify and treat the underlying cause of iron deficiency while providing supplementation. 1, 5
• Do not use oral iron in active IBD patients with hemoglobin <10 g/dL—IV iron is the appropriate first-line option. 1, 2
• Do not miss celiac disease screening—its prevalence of 3–5% in iron-deficiency cases can lead to treatment failure if undetected. 1, 5

Failure-to-Respond Algorithm

If anemia does not resolve within 6 months despite appropriate iron therapy, reassess systematically: 1

• Step 1: Verify adherence to oral therapy
• Step 2: Evaluate for ongoing blood loss (repeat endoscopy or video-capsule endoscopy)
• Step 3: Consider malabsorption syndromes (celiac disease, IBD, post-bariatric surgery)
• Step 4: Check for concurrent vitamin B12 or folate deficiency
• Step 5: Assess for systemic disease, bone-marrow pathology, or hemolysis
• Step 6: Seek hematology consultation for complex or refractory cases