Can Patients Take Ferrous Sulfate 325 mg Daily?
Yes, patients with iron deficiency can safely take ferrous sulfate 325 mg once daily, which provides 65 mg of elemental iron—this is now the preferred dosing regimen based on current evidence showing once-daily dosing is as effective as multiple daily doses while improving tolerability. 1, 2, 3
Recommended Dosing Strategy
Standard Once-Daily Dosing (Preferred)
- Take ferrous sulfate 325 mg (65 mg elemental iron) once daily for treatment of iron deficiency anemia 1, 2
- This dosing is supported by recent evidence showing that 60 mg elemental iron taken once daily stimulates hepcidin levels, which reduces subsequent iron absorption by 35-45% when taken more frequently 1, 4
- The overall iron absorption from 60 mg elemental iron once daily is similar to 60 mg taken twice daily, making multiple daily doses unnecessary 1, 4
Alternative Dosing for Specific Situations
- For patients with moderate to severe anemia requiring faster correction: 50-100 mg elemental iron daily remains appropriate 1
- For patients experiencing gastrointestinal side effects: Consider alternate-day dosing, which leads to significantly increased fractional iron absorption compared to daily dosing 1
- For patients on erythropoietin therapy (dialysis or cancer): Higher doses up to 325 mg three times daily (195 mg elemental iron total) may be needed, though this is a specialized indication 1, 5
Evidence Supporting Once-Daily Dosing
The British Society of Gastroenterology (2021) guidelines represent the most recent high-quality evidence and recommend once-daily dosing as standard practice 1. This is a significant shift from older practices that recommended multiple daily doses.
Key physiological rationale: Iron absorption triggers hepcidin production, which blocks further iron absorption for approximately 24 hours 1, 4. Taking iron more frequently than once daily therefore provides diminishing returns.
Duration of Treatment
- Continue treatment for 2 months to normalize hemoglobin 6
- Then continue for an additional 2-3 months to replenish iron stores 1, 6
- Monitor hemoglobin approximately every 4 weeks until normalized 4
- After normalization and store repletion, monitor blood counts every 6 months to detect recurrent iron deficiency 1
Important Clinical Considerations
Monitoring Response
- Expect hemoglobin to rise by at least 10 g/L within 2 weeks of starting daily oral iron therapy 4
- Absence of this rise strongly predicts subsequent treatment failure and should prompt investigation for non-adherence, malabsorption, or ongoing blood loss 4
- Ferritin levels should increase within one month in adherent patients 7
Common Pitfalls to Avoid
Do not prescribe modified-release (MR) preparations: These are considered less suitable for prescribing because iron is released beyond the duodenum and proximal jejunum where absorption is optimal 1
Avoid concurrent intake with absorption inhibitors: Patients should not take iron with dairy products, tea, coffee, or calcium-containing foods, as these significantly reduce absorption 7
Do not assume higher doses are better: Studies in cancer patients receiving erythropoietin showed that oral iron 325 mg twice daily (130 mg elemental iron) was no more effective than no iron supplementation, while IV iron was superior 1. This suggests oral iron has an absorption ceiling.
Safety Profile
Ferrous sulfate 325 mg once daily is generally well-tolerated 1. In a randomized trial comparing ferrous sulfate to iron polysaccharide complex, ferrous sulfate was actually associated with less diarrhea (35% vs 58%) and superior efficacy 8.
For patients with chronic kidney disease not on dialysis, oral ferrous sulfate is safer than IV iron, which was associated with a 2.5-fold increased risk of serious cardiovascular events and a 2.1-fold increased risk of infections requiring hospitalization 9.
When Once-Daily Dosing May Be Insufficient
Consider IV iron or higher oral doses when:
- Patient is on erythropoietin-stimulating agents (ESAs) for cancer or kidney disease 1
- Transferrin saturation remains <20% and ferritin <30 ng/mL despite oral therapy 5
- Hemoglobin fails to rise by 10 g/L after 2 weeks of adherent therapy 4
- Patient has documented malabsorption (inflammatory bowel disease, celiac disease, gastric bypass) 1