Best Medication to Replenish Low Iron
Oral ferrous sulfate 200 mg (65 mg elemental iron) once daily is the best first-line medication to replenish low iron, as it is the most cost-effective, equally efficacious as all other oral formulations, and recommended by major guidelines. 1, 2
First-Line Oral Iron Therapy
Start with ferrous sulfate 200 mg once daily immediately upon diagnosis. This formulation contains 65 mg of elemental iron and is the gold standard due to its proven effectiveness and lowest cost among all oral iron preparations. 1, 2, 3
Optimal Dosing Strategy
Take once daily, never multiple times per day. Once-daily dosing improves gastrointestinal tolerance while maintaining equal or better iron absorption compared to multiple daily doses due to hepcidin regulation. 1, 4
Add vitamin C (ascorbic acid) 500 mg with each iron dose to significantly enhance iron absorption, particularly critical when iron stores are severely depleted. 1, 3
Take on an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur. 1
Consider alternate-day dosing if daily dosing is not tolerated, as this increases fractional iron absorption and improves tolerance with similar efficacy. 1, 4
Alternative Oral Formulations
If ferrous sulfate is not tolerated, ferrous fumarate (106 mg elemental iron per 325 mg tablet) or ferrous gluconate (38 mg elemental iron per 325 mg tablet) are equally effective alternatives, though typically more expensive. 1, 5, 6 No single oral iron formulation has any therapeutic advantage over another—the choice is purely economic. 1
Expected Response and Treatment Duration
Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment. Check hemoglobin at 4 weeks to confirm response. 7, 1
Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores. Total treatment typically requires 6-7 months. 1, 3
Monitor hemoglobin and red cell indices every 3 months for the first year, then again after another year. 1
When to Switch to Intravenous Iron
Intravenous iron should replace oral therapy in specific clinical scenarios:
Absolute Indications for IV Iron
Intolerance to at least two different oral iron preparations despite trying ferrous sulfate, ferrous fumarate, and ferrous gluconate. 7, 1
Active inflammatory bowel disease with hemoglobin <10 g/dL, as inflammation-induced hepcidin elevation severely impairs oral iron absorption. 7
Post-bariatric surgery patients due to disrupted duodenal absorption mechanisms. 7, 1
Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence. 7, 1
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. 7, 3
Chronic kidney disease with functional iron deficiency (ferritin 100-300 ng/mL with transferrin saturation <20%). 1, 3
Ongoing gastrointestinal blood loss exceeding oral replacement capacity, such as with intestinal angiodysplasia. 7, 8
Second and third trimesters of pregnancy when rapid iron repletion is needed. 3
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. 7, 1 Ferric carboxymaltose (500-1000 mg single doses delivered within 15 minutes) is a preferred formulation. 1, 6
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 (infusion reactions) that respond to slowing the infusion rate. 7, 1
Special Population Considerations
Inflammatory Bowel Disease
**IV iron is first-line treatment when hemoglobin <10 g/dL with active inflammation**, as oral iron is poorly absorbed and may worsen inflammation. 7 For mild anemia (hemoglobin >10 g/dL) with clinically inactive disease, oral iron may be appropriate. 7
Pregnant Women
Start oral low-dose iron 30 mg/day at first prenatal visit for prevention. Treat anemia with 60-120 mg/day elemental iron. 1, 3 Refer pregnant women with hemoglobin <9.0 g/dL for further medical evaluation. 1
Celiac Disease
Ensure strict adherence to gluten-free diet to improve iron absorption before escalating therapy. Many patients respond to diet alone, though response can be slow. 7, 1 Progress to IV iron if oral supplementation fails despite dietary compliance. 7, 1
Portal Hypertensive Gastropathy
Start with oral iron supplementation initially, as there is no known malabsorptive defect. Switch to IV iron if profound anemia or ongoing bleeding without response to oral therapy. 7
Critical 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, 4
Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores. 1, 3
Do not overlook vitamin C supplementation when oral iron response is suboptimal, as it significantly enhances absorption. 1, 3
Do not delay treatment while awaiting diagnostic workup unless colonoscopy is scheduled within days. 1
Do not fail to identify and treat the underlying cause of iron deficiency while supplementing. 1, 8
Failure to Respond
If hemoglobin fails to rise by 2 g/dL after 4 weeks, assess for non-adherence, continued blood loss, or malabsorption. 1, 3 If anemia does not resolve within 6 months despite appropriate therapy, reassess for ongoing blood loss, evaluate for malabsorption syndromes, and consider further gastrointestinal investigation. 1