What is the recommended treatment approach for a patient diagnosed with Iron Deficiency Anemia (IDA), considering their medical history and potential underlying conditions?

Treatment of Iron Deficiency Anemia

Start oral ferrous sulfate 200 mg (65 mg elemental iron) once daily on an empty stomach with vitamin C 500 mg, and continue for 3 months after hemoglobin normalizes to replenish iron stores. 1, 2

First-Line Oral Iron Therapy

Ferrous sulfate is the preferred formulation because it is the most cost-effective option with no therapeutic advantage of any other oral iron preparation over it. 2 Each 324 mg tablet contains 65 mg of elemental iron. 3

Dosing Strategy

• Prescribe once-daily dosing, never multiple times per day. 1, 2 Once-daily dosing improves tolerance while maintaining equal or better iron absorption compared to multiple daily doses because iron doses ≥60 mg stimulate hepcidin elevation that persists for 24 hours and blocks absorption of subsequent doses by 35-45%. 2, 4

• If gastrointestinal side effects occur, switch to every-other-day dosing rather than discontinuing therapy, as alternate-day dosing significantly increases fractional iron absorption and reduces side effects while maintaining efficacy. 2, 4

• Take on an empty stomach (1-2 hours before or after meals) for optimal absorption, though taking with small amounts of food is acceptable if GI symptoms are intolerable. 2, 4

• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, especially critical when response is suboptimal. 1, 2

• Avoid coffee, tea, and calcium-containing foods for at least 1-2 hours after taking iron, as these are powerful inhibitors of iron absorption. 2, 4

Alternative Oral Formulations

• Ferrous fumarate or ferrous gluconate are equally effective alternatives if ferrous sulfate is not tolerated, though they offer no therapeutic superiority and are typically more expensive. 1, 2

Expected Response and Monitoring

• Check hemoglobin at 4 weeks, expecting a rise of approximately 2 g/dL. 1, 2 The absence of a hemoglobin rise of at least 10 g/L after 2 weeks strongly predicts treatment failure. 4

• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores, not just correct anemia. 1, 2

• Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year to detect recurrent iron deficiency. 1, 2

When to Switch to Intravenous Iron

Switch to IV iron if any of the following criteria are met:

• Intolerance to at least two different oral iron preparations despite trying alternate-day dosing. 1, 2

• Failure of hemoglobin to rise after 4 weeks of adherent oral therapy. 1, 2

• Active inflammatory bowel disease with hemoglobin <10 g/dL, as oral iron absorption is severely impaired by intestinal inflammation and hepcidin elevation. 1, 2

• Post-bariatric surgery patients due to disrupted duodenal absorption mechanisms. 1, 2

• Celiac disease with inadequate response to oral iron despite strict adherence to gluten-free diet. 1, 2

• Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%). 1, 2

• Chronic heart failure with iron deficiency, as parenteral iron may improve symptoms and quality of life. 1, 2

IV Iron Formulations

• Prefer IV iron formulations that can replace iron deficits with 1-2 infusions rather than multiple infusions, such as ferric carboxymaltose or low molecular weight iron dextran. 2, 4

• All IV iron formulations have similar overall safety profiles; true anaphylaxis is very rare (0.6-0.7%), and most reactions are complement activation-related pseudo-allergy that respond to slowing the infusion rate. 2

Investigation of Underlying Cause

Do not defer iron replacement therapy while awaiting investigations unless colonoscopy is imminent. 1

• In men and postmenopausal women, gastroscopy and colonoscopy should generally be the first-line GI investigations to exclude malignancy and other pathology. 1

• In premenopausal women, assess menstrual blood loss first, as menorrhagia accounts for iron deficiency in 5-10% of menstruating women. 2

• Screen for celiac disease with tissue transglutaminase antibodies and IgA measurement, as this is a common cause of malabsorption. 1, 2

• If bidirectional endoscopy is negative and there is inadequate response to iron replacement or recurrent IDA, investigate the small bowel with capsule endoscopy and evaluate the renal tract. 1

Special Population Considerations

Inflammatory Bowel Disease

• Treat active inflammation first to enhance iron absorption and reduce iron depletion. 1, 2

• Use IV iron as first-line treatment when hemoglobin <10 g/dL with active inflammation, as intolerance and malabsorption of oral iron are particular problems in IBD. 1, 2

Elderly Patients

• Iron deficiency is often multifactorial in the elderly. 1 Carefully consider the risks and benefits of invasive endoscopic investigations in those with major comorbidities and/or limited performance status. 1

Chronic Kidney Disease and Heart Failure

• Functional iron deficiency is common in advanced CKD and chronic heart failure. 1

• Reference specialist published guidelines for management of iron deficiency associated with CKD or CHF. 1

Post-GI or Bariatric Surgery

• IDA is common following resection or bypass surgery involving the stomach and/or small bowel. 1 A history of GI or bariatric surgery should not preclude a search for other causes of IDA. 1

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron, as this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade. 1, 2, 4

• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores. 1, 2

• Do not continue oral iron indefinitely without response—reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise. 2, 4

• Do not overlook vitamin C supplementation when oral iron response is suboptimal, as this significantly enhances absorption. 1, 2

• Do not fail to identify and treat the underlying cause of iron deficiency while supplementing. 1, 2

• Do not use enteric-coated formulations, as they may improve tolerability but significantly decrease absorption. 4

Failure to Respond

If anemia does not resolve within 6 months despite appropriate iron therapy:

• Reassess for ongoing blood loss and consider repeat endoscopic evaluation. 1, 2

• Evaluate for malabsorption syndromes including celiac disease and inflammatory bowel disease. 1, 2

• Verify patient adherence to therapy and proper administration technique. 2, 4

• Consider hematology consultation for complex cases. 2

• Long-term iron replacement therapy may be appropriate when the cause of recurrent IDA is unknown or irreversible. 1, 4