What are the recommended iron supplements for treating iron deficiency or iron deficiency anemia, including over-the-counter (OTC) and prescription options, based on dosing, efficacy, side effects, and elemental iron content?

Iron Supplement Chart for Iron Deficiency and Iron Deficiency Anemia

For most patients with iron deficiency anemia, ferrous sulfate 200 mg once daily (providing 65 mg elemental iron) is the recommended first-line treatment due to its proven efficacy, low cost, and equivalent effectiveness to more expensive formulations. 1, 2

Oral Iron Supplements Available

Standard Ferrous Salts (First-Line Options)

| Formulation | Dose per Tablet/Capsule | Elemental Iron | Recommended Dosing | Cost (28 days) | Key Features | |---|---|---|---|---| | Ferrous Sulfate | 200 mg tablet | 65 mg | 50-100 mg elemental iron once daily | £1.00 | Gold standard; most cost-effective 1, 2 | | Ferrous Fumarate | 210 mg tablet | 69 mg | 50-100 mg elemental iron once daily | £1.33 | Alternative if ferrous sulfate not tolerated 1 | | Ferrous Fumarate | 322 mg tablet | 106 mg | 50-100 mg elemental iron once daily | £1.00 | Higher elemental iron per tablet 1 | | Ferrous Gluconate | 300 mg tablet | 37 mg | 50-100 mg elemental iron once daily | £2.18 | Lower elemental iron; may need multiple tablets 1 |

Novel Oral Formulations (Second-Line Options)

| Formulation | Dose per Tablet | Elemental Iron | Recommended Dosing | Cost (28 days) | Key Features | |---|---|---|---|---| | Ferric Maltol | 30 mg tablet | 30 mg | 30 mg twice daily | £47.60 | For patients intolerant to ferrous salts; better GI tolerability 1, 2 | | Sodium Feredate (liquid) | 190 mg/5 mL | 27.5 mg/5 mL | Once daily | £8.37 | Liquid formulation option 1 |

Modified-Release Preparations (NOT Recommended)

| Formulation | Dose | Elemental Iron | Cost (28 days) | Why NOT Recommended | |---|---|---|---| | Ferrous Sulfate MR | 325 mg | 105 mg | £2.58-£3.95 | Indicated as "less suitable for prescribing" by British National Formulary; iron released beyond optimal absorption sites 1 |

Multivitamins (NOT Adequate for Treatment)

| Formulation | Elemental Iron | Cost (28 days) | Why NOT Adequate | |---|---|---| | Various multivitamins | Up to 14 mg | ~£1.00 | Insufficient elemental iron content for treating iron deficiency anemia 1 |

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Prescription Intravenous Iron Formulations

When to Use IV Iron

Intravenous iron should be considered first-line in patients with clinically active inflammatory bowel disease, previous intolerance to oral iron, hemoglobin below 10 g/dL, or conditions impairing oral iron absorption. 1, 2

| Formulation | Maximum Single Dose | Minimum Infusion Time | Total Course Dose | Key Features | |---|---|---|---| | Ferric Carboxymaltose (Injectafer) | 1,000 mg (up to 20 mg/kg) | 15 minutes | 1,500 mg (two 750 mg doses separated by ≥7 days) | Rapid administration; risk of hypophosphatemia 3, 4 | | Iron Isomaltoside | 1,000 mg (up to 20 mg/kg) | 15 minutes (for ≤1,000 mg) | Variable based on calculation | Single high-dose administration possible 1 | | Iron Sucrose | 200-500 mg | 30-210 minutes | Requires multiple doses | Established safety profile; requires repeated dosing 1 | | Ferric Gluconate | 125 mg | 60 minutes | Requires multiple doses | Lower dose per infusion 1 |

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Efficacy Comparison

Expected Response to Oral Iron

• Hemoglobin should increase by at least 10 g/L after 2 weeks of daily oral iron therapy (sensitivity 90.1%, specificity 79.3% for predicting adequate response) 1, 2
• Target increase: approximately 1-2 g/dL within 3-4 weeks 1, 2
• Treatment duration: Continue for 3 months after hemoglobin normalization to replenish iron stores 1, 2

Oral vs. IV Iron Efficacy

• IV iron produces faster hemoglobin response and greater ferritin increment compared to oral iron 1
• IV iron can produce clinically meaningful hemoglobin response within 1 week 1
• Ferric maltol normalized hemoglobin in 63-66% of cases after 12 weeks, and 89% after 1 year 1

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Side Effects Profile

Oral Iron Side Effects (Dose-Dependent)

| Formulation Type | Common Side Effects | Frequency | Management Strategy | |---|---|---| | Ferrous Salts (sulfate, fumarate, gluconate) | Constipation, nausea, abdominal discomfort, dark stools | Higher with multiple daily doses 1, 2 | Switch to once-daily dosing or alternate-day dosing; take with food if needed 2 | | Ferric Maltol | GI side effects comparable to placebo 1 | Lower than ferrous salts 1 | Better tolerated; consider for patients intolerant to ferrous salts 1 |

IV Iron Side Effects

| Formulation | Serious Risks | Common Side Effects | Special Monitoring | |---|---|---| | Ferric Carboxymaltose | Hypersensitivity reactions (rare); hypophosphatemia | Injection site reactions, headache | Monitor serum phosphate levels, especially with repeat courses within 3 months 3, 4 | | Iron Dextran | Anaphylactic reactions (requires test dose) 1 | Injection site reactions | Test dose mandatory 1 | | Iron Sucrose, Iron Isomaltoside | Hypersensitivity reactions (rare) | Injection site reactions, nausea | Standard monitoring 1 |

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Optimal Dosing Strategies to Maximize Efficacy and Minimize Side Effects

Once-Daily Dosing (Preferred)

Take 50-100 mg elemental iron once daily in the morning on an empty stomach 1, 2

• Rationale: Hepcidin levels increase after iron intake and remain elevated for 48 hours, blocking further absorption 2
• Multiple daily doses increase side effects without improving absorption 2

Alternate-Day Dosing (If Daily Not Tolerated)

Consider 100-200 mg elemental iron every other day 1, 2

• Efficacy: Produces similar hemoglobin increment after equivalent total dose with significantly lower nausea rates 1
• Absorption: Significantly increased fractional iron absorption compared to daily dosing 2

Strategies to Enhance Absorption

• Take with vitamin C (250-500 mg) to enhance absorption by forming iron chelate 1, 2
• Avoid taking with tea, coffee, or calcium-containing foods/medications which inhibit absorption 2
• Take on empty stomach (1-2 hours before or after meals) for maximum absorption 2

If Standard Doses Not Tolerated

1. Reduce dose to 50 mg elemental iron once daily 2
2. Take with food (reduces absorption but improves tolerability) 2
3. Switch to ferric maltol (30 mg twice daily) 1, 2
4. Consider alternate-day dosing 1, 2
5. Switch to IV iron if oral modifications fail 1, 2

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Special Population Considerations

Chronic Kidney Disease (Not on Dialysis)

• Ferric citrate (Auryxia): 210 mg elemental iron, 1 tablet 3 times daily with meals 1
• Standard ferrous salts: 1,000 mg/day ferrous sulfate for IDA in CKD 1

Inflammatory Bowel Disease

• IV iron is first-line for clinically active disease 1
• Oral iron may be used only in mild anemia with clinically inactive disease (hemoglobin 11.0-12.9 g/dL in men, 11.0-11.9 g/dL in women) 1
• Avoid oral iron in active IBD due to potential mucosal harm and disease exacerbation 1

Cancer Patients

• Oral iron only for patients with absolute iron deficiency (ferritin <100 ng/mL) AND non-inflammatory conditions (CRP <5 mg/L) 1
• IV iron preferred for most cancer patients due to inflammation 1

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Critical Monitoring Parameters

Initial Response Assessment

• Check hemoglobin at 2 weeks: Failure to increase by ≥10 g/L predicts treatment failure 1, 2
• Check hemoglobin at 4 weeks: Expected increase of 1-2 g/dL 1, 2

Causes of Treatment Failure

1. Non-compliance (most common) 1
2. Continued blood loss 1
3. Malabsorption 1
4. Misdiagnosis 1
5. Concurrent B12 or folate deficiency 1

Long-Term Monitoring

• Continue treatment for 3 months after hemoglobin normalization 1, 2
• Monitor hemoglobin every 3 months for 1 year, then annually 1
• For IV iron: Monitor serum phosphate with repeat courses, especially within 3 months 3

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Common Pitfalls to Avoid

1. Prescribing multiple daily doses of oral iron – increases side effects without improving absorption due to hepcidin regulation 2
2. Using modified-release preparations – iron released beyond optimal absorption sites; less suitable for prescribing 1
3. Relying on multivitamins for treatment – insufficient elemental iron content (≤14 mg) 1
4. Administering IV iron during active infections – excluded from clinical trials; withhold until infection resolves 1
5. Not monitoring phosphate levels with ferric carboxymaltose – significant risk of hypophosphatemia, especially with repeat courses 3, 4
6. Taking iron with calcium, tea, or coffee – significantly reduces absorption 2
7. Stopping treatment when hemoglobin normalizes – must continue for 3 months to replenish iron stores 1, 2