What is the outpatient regimen for iron‑deficiency anemia?

Outpatient Oral Iron Regimen for Iron-Deficiency Anemia

Start with ferrous sulfate 200 mg (approximately 65 mg elemental iron) once daily, taken on an empty stomach in the morning, and continue for 3 months after hemoglobin normalizes to replenish iron stores. 1, 2

Initial Prescription

• Ferrous sulfate 200 mg once daily is the most cost-effective first-line option, providing 50–100 mg elemental iron per dose 1, 2
• Ferrous gluconate and ferrous fumarate are equally effective alternatives if ferrous sulfate is unavailable 1
• Once-daily dosing is superior to multiple daily doses because hepcidin rises after iron intake and remains elevated for 48 hours, blocking further absorption and increasing side effects without benefit 1, 2

Timing and Administration

• Take on an empty stomach in the morning to maximize absorption 1, 2
• If gastrointestinal intolerance occurs, the patient may take iron with meals (though absorption decreases) or consider taking with meat protein to enhance uptake 1
• Avoid tea or coffee within 1 hour of iron ingestion, as they markedly inhibit absorption 2

Vitamin C Supplementation

• Vitamin C is optional but may modestly improve absorption 1, 2
• If used, prescribe 500 mg vitamin C taken separately or advise consumption of vitamin C-rich foods 1, 2
• Earlier guidelines emphasized ascorbic acid enhancement, but recent evidence shows it is not essential for treatment success 1, 2

Alternate-Day Dosing Strategy

• Consider alternate-day dosing (120 mg elemental iron every other day) if the patient experiences significant nausea or gastrointestinal side effects 1, 2, 3
• Alternate-day dosing produces similar hemoglobin increments with markedly lower nausea rates (relative risk 0.56 for GI adverse events) 1, 3
• This regimen may be slightly slower for repleting iron stores but improves compliance 1, 3

Monitoring Schedule

• Check hemoglobin at 2 weeks: failure to achieve at least a 10 g/L (1 g/dL) rise predicts subsequent treatment failure with 90.1% sensitivity and 79.3% specificity 1, 2, 4
• Recheck hemoglobin every 4 weeks until values normalize 1, 2
• After hemoglobin correction, continue oral iron for an additional 2–3 months to replenish iron stores 1, 5
• Monitor hemoglobin and red cell indices every 3 months for the first year, then every 6–12 months thereafter to detect recurrence 1, 5

When to Switch to Intravenous Iron

Transition to IV iron if any of the following occur:

• Inadequate hemoglobin response (less than 10 g/L rise) after 2 weeks of oral therapy 1, 2, 4
• Intolerance to at least two different oral iron preparations 2
• Clinically active inflammatory bowel disease or other gastrointestinal inflammatory pathology where parenteral iron is more effective 1
• Hemoglobin below 100 g/L at presentation 1
• Chronic disease, ongoing blood loss, or malabsorption conditions 1, 2
• Patient preference in the setting of severe oral intolerance 1

Available IV formulations include ferric carboxymaltose (1000 mg single dose over 15 minutes), ferric derisomaltose, iron sucrose, and iron dextran 6

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses—this increases side effects without improving absorption due to hepcidin-mediated blockade 1, 2
• Do not switch between different ferrous salts (e.g., from ferrous sulfate to ferrous gluconate) for intolerance, as there is no evidence of superiority; instead, try alternate-day dosing, ferric maltol, or IV iron 1
• Always investigate the underlying cause of iron deficiency: menstrual loss, dietary insufficiency, celiac disease, Helicobacter pylori infection, or gastrointestinal blood loss 1
• Do not use modified-release preparations, as they are less suitable for prescribing 1
• Avoid faecal occult blood testing, which is insensitive and non-specific for diagnosing the cause of iron deficiency 1

Special Populations

• Premenopausal women with menorrhagia: Treat with oral iron as first-line; consider gynecologic evaluation if anemia persists despite adequate supplementation 1
• Inflammatory bowel disease patients: Use IV iron as first-line if disease is clinically active, hemoglobin is below 100 g/L, or previous oral intolerance occurred 1
• Patients with chronic kidney disease (non-dialysis): IV iron is often preferred, but oral iron may be trialed first in stable patients 6

Expected Response and Quality of Life

• Hemoglobin should rise by at least 10 g/L within 2 weeks and normalize within 4–8 weeks 1, 4
• Quality of life improves with correction of anemia, independent of underlying disease activity 1
• Fatigue reduction is a key benefit of successful iron repletion 4