Is Ferrous Sulfate 325 mg Safe for Daily Dosing?
Yes, ferrous sulfate 325 mg (containing 65 mg elemental iron) is safe for daily dosing in adults with iron deficiency anemia, and current guidelines recommend once-daily dosing as the optimal regimen. 1, 2
Recommended Dosing Strategy
The preferred approach is 50-100 mg elemental iron once daily, taken on an empty stomach, which translates to one ferrous sulfate 325 mg tablet (65 mg elemental iron) daily. 1, 2 This represents a shift from older recommendations that advocated for multiple daily doses or higher total daily amounts.
Key Dosing Principles:
Once-daily dosing is superior to multiple daily doses because divided doses increase serum hepcidin levels, which paradoxically reduces iron absorption from subsequent doses throughout the day 1, 3
Alternate-day dosing may be equally or more effective than consecutive daily dosing with better tolerability, as it allows hepcidin levels to normalize between doses and results in 21.8% fractional absorption versus 16.3% with daily dosing 1, 3
Taking iron in the fasting state maximizes absorption, as food can reduce absorption by up to 50% 2
Adding vitamin C to oral iron supplementation improves absorption and should be considered 1
Safety Profile
Ferrous sulfate 325 mg daily is well-tolerated with minimal serious adverse effects:
No grade 3 or 4 adverse events were reported in controlled trials of daily ferrous sulfate dosing 3
Common side effects are gastrointestinal (nausea, flatulence, diarrhea, gastric discomfort) but are generally mild and can be managed by switching to alternate-day dosing if needed 1
The 325 mg tablet provides 362% of the U.S. recommended daily intake, but this is appropriate for treating iron deficiency anemia, not for routine supplementation 4
Monitoring and Duration
Treatment should continue for approximately 3 months after hemoglobin normalization to adequately replenish iron stores 2, 5
Monitoring Schedule:
Check hemoglobin after 2-4 weeks of treatment to assess response 2
Absence of a hemoglobin rise of at least 10 g/L after 2 weeks is strongly predictive of treatment failure (sensitivity 90.1%, specificity 79.3%) and warrants investigation for non-compliance, malabsorption, ongoing bleeding, or consideration of intravenous iron 1
After successful treatment, monitor blood counts every 6 months initially to detect recurrent iron deficiency 1, 2
When to Switch to Intravenous Iron
Intravenous iron should be used instead of oral iron in specific circumstances: 1
- Patient does not tolerate oral iron despite alternate-day dosing attempts
- Ferritin levels do not improve after an adequate trial of oral iron (typically 2 weeks)
- Severe anemia (hemoglobin <10 g/dL or 100 g/L) 1
- Conditions impairing absorption: inflammatory bowel disease with active inflammation, celiac disease, post-bariatric surgery 1
- Ongoing significant blood loss
- Pregnancy (second and third trimesters) 5
Common Pitfalls to Avoid
Do not prescribe modified-release or enteric-coated preparations as they are less suitable for prescribing, more expensive, and may release iron beyond the duodenum where absorption is optimal 1
Do not automatically switch to a different oral iron salt (ferrous gluconate, ferrous fumarate) if the patient reports side effects, as there is no evidence this improves tolerability; instead, try alternate-day dosing 1
Do not take iron with food, calcium supplements, antacids, or proton pump inhibitors as these significantly reduce absorption 2
Do not continue oral iron indefinitely without monitoring response, as failure to respond may indicate underlying pathology requiring investigation 1
Cost Considerations
Ferrous sulfate is the most cost-effective oral iron preparation at approximately £2.50 for 28 days of treatment, compared to ferrous fumarate (£1.00-£4.00) or ferric maltol (£47.60) 1