What is the recommended iron replacement regimen for patients with iron deficiency?

Iron Replacement Regimen

Start with oral ferrous sulfate 200 mg (65 mg elemental iron) once daily on an empty stomach, adding vitamin C to enhance absorption; if not tolerated or ineffective after 2 weeks, switch to intravenous iron rather than trying alternative oral formulations. 1, 2

First-Line Oral Iron Therapy

Preferred Agent and Dosing

• Ferrous sulfate is the recommended first-line agent because it is the least expensive option with no proven advantages of other formulations over it 1, 2
• Standard dose: 50-100 mg elemental iron once daily (one ferrous sulfate 200 mg tablet = 65 mg elemental iron) 1, 2
• Take on an empty stomach (1-2 hours before or after meals) to maximize absorption 2

Enhancing Absorption

• Add vitamin C (250-500 mg) with each iron dose to improve absorption by forming an iron chelate 1, 2
• Avoid taking iron with tea, coffee, or calcium-containing products which inhibit absorption 2

Alternative Dosing for Intolerance

• If daily dosing causes intolerable gastrointestinal side effects, switch to every-other-day dosing rather than multiple daily doses 1
• Alternate-day dosing leads to significantly increased fractional iron absorption compared to daily dosing and may be better tolerated 1, 2
• Do not prescribe multiple daily doses - this increases side effects without improving absorption due to hepcidin-mediated blockade of iron absorption for 48 hours after each dose 2

Monitoring Response

Early Assessment

• Check hemoglobin after 2 weeks of treatment - expect at least a 10 g/L (1 g/dL) increase if therapy is working 1, 2
• Absence of a 10 g/L rise after 2 weeks strongly predicts treatment failure (sensitivity 90.1%, specificity 79.3%) 1
• Recheck hemoglobin at 4 weeks to confirm ongoing response 1, 2

Duration of Treatment

• Continue oral iron for approximately 3 months after hemoglobin normalizes to replenish iron stores 1, 2
• After successful treatment, monitor blood count every 6 months initially to detect recurrent iron deficiency 1

When to Switch to Intravenous Iron

Absolute Indications

• Hemoglobin <100 g/L (10 g/dL) - IV iron should be first-line treatment 1
• Active inflammatory bowel disease - oral iron is poorly absorbed and may worsen inflammation 1
• Post-bariatric surgery patients with disrupted duodenal absorption 1
• Intolerance to oral iron despite dosing modifications 1
• Failure to respond to oral iron (ferritin not improving or no hemoglobin rise after 2 weeks) 1

Relative Indications

• Ongoing blood loss requiring rapid iron repletion 3
• Second or third trimester of pregnancy 3
• Chronic kidney disease, heart failure, or cancer with active inflammation 1, 3
• Need for erythropoiesis-stimulating agents 1

IV Iron Formulations

• Prefer formulations requiring 1-2 infusions over those requiring multiple doses 1
• Iron sucrose: 100-200 mg per dose for hemodialysis patients; up to 500 mg infusion for non-dialysis patients 4
• Ferric gluconate: 125 mg per dialysis session for adults; 1.5 mg/kg for pediatric patients 5
• All IV iron formulations have similar safety profiles - true anaphylaxis is very rare 1

Alternative Oral Formulations (Second-Line)

When Standard Ferrous Salts Fail

• Ferric maltol 30 mg twice daily may be considered for patients with previous intolerance to traditional iron salts, particularly in inflammatory bowel disease 1
• However, ferric maltol costs approximately £47.60 vs £1.00 for ferrous sulfate per 28-day supply, making it considerably more expensive 1
• Ferrous fumarate (69-106 mg elemental iron per tablet) or ferrous gluconate (37 mg elemental iron per tablet) are alternatives, though evidence does not support switching between traditional iron salts for intolerance 1, 2

Formulations to Avoid

• Modified-release preparations are less suitable for prescribing according to the British National Formulary 1
• Multivitamin preparations contain insufficient iron (typically ≤14 mg elemental iron) for treating iron deficiency anemia 1, 2

Special Populations

Inflammatory Bowel Disease

• Oral iron is first-line only if disease is clinically inactive, anemia is mild, and patient has not previously been intolerant to oral iron 1
• IV iron is first-line for active IBD, hemoglobin <100 g/L, or previous oral iron intolerance 1
• After successful IV iron treatment, re-treat when ferritin drops below 100 μg/L or hemoglobin falls below 120 g/L (women) or 130 g/L (men) 1

Cancer-Associated Anemia

• Baseline and periodic monitoring of iron parameters (ferritin, transferrin saturation, TIBC) is recommended for patients receiving erythropoiesis-stimulating agents 1
• Iron supplementation reduces RBC transfusion requirements in patients receiving ESAs, independent of baseline iron status 1
• Both oral and IV iron are acceptable; IV iron may be superior for improving hemoglobin but has higher costs and risk of hypotension 1

Common Pitfalls to Avoid

• Do not prescribe iron two or three times daily - once daily or alternate-day dosing is equally or more effective with fewer side effects 1, 2
• Do not switch between different ferrous salts for intolerance - this practice is not evidence-based; instead, try alternate-day dosing or switch to IV iron 1
• Do not delay iron replacement while awaiting diagnostic workup unless colonoscopy is imminent 1
• Do not use blood transfusion for iron deficiency anemia unless patient has severe symptomatic anemia or circulatory compromise - IV iron produces meaningful hemoglobin response within one week 1
• Do not continue oral iron beyond 2 weeks without documented hemoglobin response - this indicates malabsorption, continued bleeding, or other pathology requiring investigation 1