How is iron replaced in a patient with iron deficiency anemia?

Iron Replacement in Iron Deficiency Anemia

Start with oral ferrous sulfate 200 mg once daily as first-line therapy for most patients with iron deficiency anemia, and switch to intravenous iron if oral therapy fails, is not tolerated, or in specific clinical situations requiring rapid repletion. 1

Oral Iron Therapy: First-Line Treatment

Choice of Formulation

• Ferrous sulfate is the preferred oral iron preparation because it is the least expensive and equally effective as other formulations 1
• No single oral iron formulation has proven superiority over others in effectiveness or tolerance 1
• Alternative ferrous salts (ferrous fumarate, ferrous gluconate) are equally effective if ferrous sulfate is not tolerated 1
• Each ferrous sulfate 324 mg tablet contains 65 mg of elemental iron 2

Optimal Dosing Strategy

• Give oral iron once daily at most—taking iron more frequently increases side effects without improving absorption because hepcidin levels remain elevated for up to 48 hours after each dose 1
• Consider every-other-day dosing for patients with poor tolerance, as this may improve adherence with similar absorption rates 1
• Traditional dosing of 200 mg three times daily is outdated; lower doses are equally effective and better tolerated 1

Enhancing Absorption

• Add vitamin C (80-500 mg) to improve iron absorption, particularly when taken on an empty stomach 1
• Avoid tea and coffee within one hour of taking iron as they powerfully inhibit absorption 1
• Taking iron on an empty stomach optimizes absorption, though food may be necessary if gastrointestinal side effects occur 1

Expected Response and Duration

• Hemoglobin should increase by 1-2 g/dL within 2-4 weeks of starting therapy 1
• Ferritin levels should rise within one month in adherent patients 1
• Continue oral iron for 3 months after anemia correction to replenish iron stores 1

Common Side Effects

• Constipation occurs in 12% of patients, diarrhea in 8%, and nausea in 11% 1
• Side effects are the primary reason for non-adherence 1

Intravenous Iron: When to Switch

Clear Indications for IV Iron

Use intravenous iron as first-line therapy in the following situations: 1

• Intolerance to oral iron (after trying at least two different oral formulations) 1
• Failure to respond to oral iron: hemoglobin not increasing by 1 g/dL within 2 weeks or ferritin not rising within one month 1
• Active inflammatory bowel disease with compromised absorption 1
• Post-bariatric surgery patients with disrupted duodenal absorption 1
• Hemoglobin below 100 g/L (10 g/dL) 1
• Ongoing blood loss exceeding oral iron absorption capacity 1
• Need for rapid correction prior to surgery or other urgent situations 3

IV Iron Formulations

• Prefer formulations that can replace iron deficits in 1-2 infusions rather than multiple doses 1
• Ferric carboxymaltose and ferric derisomaltose allow high single doses (500-1000 mg) 1, 3
• Iron sucrose requires multiple smaller doses (200 mg maximum per infusion) 1
• All IV formulations have similar overall efficacy and safety profiles 1

Safety Considerations

• True anaphylaxis to IV iron is extremely rare (approximately 1:200,000) 1
• Most reactions are complement activation-related pseudo-allergy (infusion reactions), not true allergies 1
• For mild reactions: stop the infusion and restart 15 minutes later at a slower rate 1
• For severe reactions: consider corticosteroids; avoid diphenhydramine as its side effects can mimic worsening reactions 1
• Monitor phosphate levels, especially with ferric carboxymaltose, due to risk of hypophosphatemia 3
• Always administer in facilities equipped for managing hypersensitivity reactions 1, 3

Special Populations

Inflammatory Bowel Disease

• Oral iron may be used in patients with mild anemia and clinically inactive disease who have not previously been intolerant 1
• IV iron is first-line for active IBD regardless of hemoglobin level 1
• Treat active inflammation to enhance iron absorption and reduce depletion 1

Post-Bariatric Surgery

• IV iron is preferred due to disrupted duodenal absorption mechanisms 1

Premenopausal Women

• Menstrual loss is the most common cause of iron deficiency in this population 1
• Oral iron is typically appropriate as first-line therapy 1

Monitoring and Follow-Up

• Monitor hemoglobin and red cell indices every 3 months for the first year, then annually 1
• Check ferritin if hemoglobin or MCV falls below normal 1
• After successful IV iron treatment, reinitiate therapy when ferritin drops below 100 μg/L or hemoglobin falls below gender-specific thresholds (12 g/dL for women, 13 g/dL for men) 1

Critical Pitfalls to Avoid

• Do not prescribe iron more than once daily—this increases side effects without improving absorption due to hepcidin elevation 1
• Do not use parenteral iron as first-line unless specific indications exist—it is substantially more expensive than oral formulations 1
• Do not assume all IV iron reactions are allergies—most are infusion reactions that can be managed by slowing the rate 1
• Do not stop iron therapy once hemoglobin normalizes—continue for 3 months to replenish stores 1
• Do not forget to address the underlying cause of iron deficiency while replacing iron 1