Is Twice-Daily Ferrex Safe?
No, twice-daily dosing of Ferrex (iron polysaccharide) is not recommended and offers no advantage over once-daily dosing—in fact, it reduces absorption efficiency and increases side effects without improving outcomes. The FDA-approved labeling for iron polysaccharide explicitly states "One capsule daily" as the recommended dose, not twice daily. 1
Why Once-Daily Dosing Is Superior
Hepcidin blocks subsequent iron absorption: When you take ≥60 mg elemental iron in a single dose, your body releases hepcidin, a regulatory hormone that remains elevated for approximately 24 hours and blocks further iron uptake by 35–45%. 2, 3
Twice-daily dosing wastes the second dose: Taking iron more frequently than once daily provides diminishing returns—the second dose is absorbed at only 55–65% the efficiency of the first dose due to hepcidin-mediated blockade. 2
Gastrointestinal side effects increase: Multiple daily doses significantly increase nausea, constipation, and abdominal discomfort compared to single daily dosing, without improving hemoglobin response. 4, 2
Evidence Comparing Ferrex to Standard Ferrous Salts
The highest-quality head-to-head trial demonstrates that ferrous sulfate is superior to iron polysaccharide complex in every measurable outcome:
In a 2017 randomized controlled trial in children with iron-deficiency anemia, ferrous sulfate produced a 1.0 g/dL greater increase in hemoglobin at 12 weeks compared to iron polysaccharide complex (11.9 vs 11.1 g/dL; P < .001). 5
Ferrous sulfate achieved complete resolution of anemia in 29% vs only 6% with iron polysaccharide (P = .04). 5
Ferrous sulfate increased ferritin by 10.2 ng/mL more than iron polysaccharide (P < .001), indicating superior iron store repletion. 5
Iron polysaccharide caused more diarrhea (58% vs 35%; P = .04), contradicting the common belief that it is better tolerated. 5
A 2004 Taiwanese study similarly found ferrous fumarate "significantly more effective" than iron polysaccharide complex for both hemoglobin and ferritin endpoints. 6
What You Should Prescribe Instead
Switch to ferrous sulfate 325 mg (65 mg elemental iron) once daily, taken on an empty stomach in the morning, 1–2 hours before meals. 2, 3
Ferrous sulfate is the gold-standard, most cost-effective formulation (£1.00 vs £47.60 per 28 days for alternative formulations). 4, 2
Once-daily dosing of 50–100 mg elemental iron is the evidence-based standard recommended by the British Society of Gastroenterology. 4, 2
If gastrointestinal side effects occur with daily dosing, switch to alternate-day dosing (every other day) with 100–200 mg elemental iron—this markedly increases fractional absorption and reduces side effects while preserving efficacy. 4, 2
Monitoring for Treatment Success
Check hemoglobin 2 weeks after starting therapy—an increase of ≥10 g/L predicts treatment success with 90% sensitivity and 79% specificity. 4, 2
Failure to achieve this 10 g/L rise strongly predicts eventual treatment failure and warrants investigation for non-adherence, malabsorption, ongoing blood loss, or concurrent vitamin B12/folate deficiency. 2, 7
After hemoglobin normalizes, continue iron for 3 additional months to fully replenish bone marrow iron stores. 2, 7
Common Pitfalls to Avoid
Do not prescribe modified-release iron preparations—they release iron beyond the duodenum where absorption is optimal and are marked "less suitable for prescribing" by the British National Formulary. 4, 2
Do not rely on multivitamin preparations containing ≤14 mg elemental iron—these are insufficient for treating iron-deficiency anemia. 2, 7
Do not continue oral iron indefinitely without monitoring—failure to respond may indicate a need for intravenous iron, which produces a clinically meaningful hemoglobin response within one week. 4, 2