What is the difference between ferrous (iron) sulphate and ferrous (iron) fumarate for treating iron deficiency in a teenager?

Ferrous Sulfate vs Ferrous Fumarate for Iron Deficiency in Teenagers

Ferrous sulfate is the preferred first-line treatment for iron deficiency in teenagers because it is the least expensive formulation with equivalent efficacy to ferrous fumarate, and no evidence demonstrates any therapeutic advantage of one over the other. 1, 2

Key Differences Between the Two Formulations

Elemental Iron Content

• Ferrous sulfate 325 mg tablets contain 65 mg elemental iron 2
• Ferrous fumarate 325 mg tablets contain 106 mg elemental iron 2
• Despite the higher elemental iron content in ferrous fumarate, this does not translate to superior clinical outcomes 1, 2

Cost-Effectiveness

• Ferrous sulfate is consistently the least expensive oral iron formulation available, making it the most cost-effective choice for treating iron deficiency 1, 2
• Ferrous fumarate is typically more expensive with no proven therapeutic benefit to justify the additional cost 2

Absorption and Bioavailability

• In iron-sufficient adolescents and adults, ferrous fumarate and ferrous sulfate have equivalent absorption (relative bioavailability 86-106%) 3
• However, in iron-deficient young children, ferrous fumarate may be absorbed only 30% as well as ferrous sulfate 4
• The mechanism for this age-related difference is unclear but may relate to reduced gastric acid secretion in younger children or differential upregulation of iron absorption pathways 4
• For teenagers, this absorption difference is likely not clinically significant, as they have adult-like gastric physiology 3

Tolerability and Side Effects

• Both formulations have similar gastrointestinal side effect profiles, including constipation (12%), diarrhea (8%), and nausea (11%) 1
• Some studies suggest slightly fewer gastrointestinal side effects with ferrous fumarate, but the difference is minimal and not consistently demonstrated across trials 5, 6
• No evidence supports that ferrous fumarate is better tolerated than ferrous sulfate in clinical practice 1, 2

Clinical Efficacy

• Both formulations produce similar increases in hemoglobin levels (approximately 2 g/dL after 3-4 weeks of treatment) 1, 2, 6
• No single oral iron formulation has any therapeutic advantage over another—the choice is purely economic 2

Recommended Treatment Approach for Teenagers

First-Line Therapy

• Prescribe ferrous sulfate 200 mg (65 mg elemental iron) once daily 1, 2
• Once-daily dosing is superior to multiple daily doses because hepcidin levels remain elevated for 48 hours after iron intake, blocking further absorption 1, 2
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption 1, 2

If Ferrous Sulfate Is Not Tolerated

• Switch to ferrous fumarate as an alternative formulation, recognizing it is equally effective but typically more expensive 1, 2
• Alternatively, consider ferrous gluconate (38 mg elemental iron per 325 mg tablet) 2

Expected Response and Monitoring

• Check hemoglobin at 4 weeks, expecting a rise of approximately 2 g/dL 1, 2
• Continue oral iron for 3 months after hemoglobin normalizes to fully replenish iron stores 1, 2

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses—this increases side effects without improving efficacy due to hepcidin-mediated absorption blockade 1, 2
• Do not assume ferrous fumarate is better tolerated based on its higher elemental iron content—clinical evidence does not support this 1, 2
• Do not stop iron therapy when hemoglobin normalizes—continue for 3 months to replenish stores 1, 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1, 2

When to Consider Intravenous Iron

Switch to IV iron if the teenager meets any of these criteria:

• Intolerance to at least two different oral iron preparations 1, 2
• Failure of ferritin levels to improve after 4 weeks of compliant oral therapy 2
• Active inflammatory bowel disease with hemoglobin <10 g/dL 1, 2
• Post-bariatric surgery with disrupted duodenal absorption 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2