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Iron Supplementation

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Iron Supplementation, Iron Replacement, Ferrous Sulfate, Iron Sulfate, Ferrous Gluconate, Feosol, Fer-In-Sol, Ferrous Fumarate, Hemocyte, Ferric Compounds

  • See also
  1. Dietary Iron
  2. Iron
  3. Hemochromatosis
  4. Iron Deficiency Anemia
  5. Acute Iron Toxicity
  • Indications
  1. Iron Deficiency Anemia
  • Physiology
  1. Daily Iron absorption and utilization is limited
    1. Bone Marrow response limited to 20 mg/day elemental iron
    2. Hepcidin is secreted by the liver in response to oral iron intake
      1. Hepcidin suppresses iron absorption for the next 24-48 hours after Iron Ingestion
      2. Hepcidin triggers ferroportin degradation in enterocytes and Macrophages
      3. Hepcidin is also increased in chronic disease (e.g. CHF, CKD, infection)
      4. Iron intake more than once daily is unlikely to significantly raise body iron stores
        1. Iron taken every other day may be just as effective as once daily iron intake
  2. Iron absorption is reduced with medications and supplements
    1. Iron absorption reduced up to 40% when taken with meals (also reduced with Calcium, tea, coffee)
    2. Further absorption is reduced with gastric acid hyposecretion (e.g. Proton Pump Inhibitor use)
  • Precautions
  1. Iron supplements in overdosage may be lethal in children (FDA black box warning)
    1. See Iron Ingestion
  2. Ferrous Sulfate and Ferrous Fumarate are preferred preparations
    1. Delivers highest elemental iron amounts
    2. Ferrous Gluconate supplies only 50% of the elemntal iron
  3. Formulations with risk of lower iron absorption
    1. Extended release or enteric coated iron formulations
  4. Formulations with no evidence of benefit
    1. Polysaccharide-iron complex (e.g. Ferrex 150)
    2. Carbonyl iron (ICAR)
    3. Heme Iron Polypeptide (Proferrin ES)
  5. Some guidelines recommend avoiding every other day dosing
    1. Reasoning
      1. When same dose is taken every other day instead of daily, does not decrease gastrointestinal side effects
      2. Although absorption may increase with every day dosing, the total time for replacement is still twice as long
      3. Compliance decreases with every other day dosing
    2. However, physiologically, Hepcidin inhibits iron utilization for 24-48 hours after ingestion (see physiology above)
      1. Therefore, every other day dosing may actually be reasonable
  6. References
    1. (2017) Presc Lett 24(3)
    2. (2020) Presc Lett 27(9): 52-3
  • Preparations
  1. Ferrous Fumarate (33% elemental iron)
    1. Elemental Iron: 106 mg per 325 mg tablet (or 29.5 mg per 90 mg tablet)
  2. Ferrous Sulfate (FeSO4, 20% elemental iron)
    1. Elemental Iron: 15 mg per 75 mg/0.6 ml Dropper
    2. Elemental Iron: 60 mg per 300 mg/5 ml Syrup
    3. Elemental Iron: 44 mg per 220 mg/5 ml Elixir/Liquid
    4. Elemental Iron: 65 mg per 325 mg Tablet (or 60 mg per 300 mg tablet)
  3. Ferrous Gluconate (Fergon, 12% elemental iron)
    1. May be better tolerated that other forms, but supplies only 50% of the iron in other formulations
    2. Elemental Iron: 36 mg per 325 mg tablet (or 27 mg per 240 mg tablet)
    3. Elemental Iron: 30 mg per 300 mg/5 ml syrup
  4. Parenteral Iron
    1. See Parenteral Iron
    2. Iron sucrose (Venofer)
    3. Iron Dextran (Imferon)
    4. Sodium Ferric Gluconate (Ferrlecit)
    5. Ferumoxytol (Feraheme)
    6. Ferric Carboxymaltose (Injectafer)
  • Dosing
  1. General Anemia management (adults)
    1. Ferrous Sulfate
      1. Standard Dose: 325 mg orally daily (65 to 100 mg elemental iron daily)
      2. Lower dose: 15-20 mg elemental iron
        1. Low dose (15-20 mg) is as effective as 65-130 mg/day with less adverse effects
        2. Lo (2023) Eur J Haematol 110(2):123-30 +PMID: 36336470 [PubMed]
  2. Pediatric Anemia
    1. Severe Pediatric Anemia
      1. Ferrous Sulfate 4-6 mg/kg/day PO tid
    2. Mild Pediatric Anemia or Prophylaxis
      1. Ferrous Sulfate 1-2 mg/kg/day PO qd-bid
    3. Overall daily dietary requirements (or supplementation) in non-anemic children
      1. Preterm Infants (born <37 weeks) age <12 months
        1. Exclusively Breast fed: 2 mg/kg/day
        2. Iron-fortified formula: 1 mg/kg/day
      2. Term infants age <12 months
        1. Exclusively Breast fed: 1 mg/kg/day
        2. Iron-fortified formula: No additional needed
      3. Children age 1 to 3 years
        1. Requirement: 7 mg/day elemental iron total via diet or supplementation
      4. Children age 4 to 8 years
        1. Requirement: 10 mg/day elemental iron total via diet or supplementation
  3. Postpartum Iron Deficiency Anemia (older protocol, replaced by lower dosing, less frequently as above)
    1. Hemoglobin 7-9
      1. Ferrous Sulfate 325 mg orally three times daily
    2. Hemoglobin 9-10
      1. Ferrous Sulfate 325mg orally twice daily
    3. Hemoglobin >10
      1. Ferrous Sulfate 325mg orally twice daily
  • Drug Interactions
  1. Food and drugs reducing iron absorption
    1. Antacids (raise pH, low acidity)
      1. Tums, Maalox, or Mylanta
      2. Histamine H2 Receptor Blockers (e.g. Ranitidine)
      3. Proton Pump Inhibitors (e.g. Prilosec)
    2. Inhibitors of iron absorption
      1. Polyphenol (in vegetables)
      2. Tannins (in tea)
      3. Phytate (in bran, cereal)
      4. Calcium (dairy products)
  2. Drugs increasing iron absorption
    1. Vitamin C (Ascorbic Acid) 200 mg or orange juice 8 ounces increases iron absorption by 10% (minimal)
  3. Drugs with decreased absorption when taken with iron
    1. Levodopa
    2. Methyldopa
    3. Penicillamine
    4. Quinolones
    5. Tetracyclines
  • Adverse Effects
  1. Gastrointestinal distress
    1. Ferrous iron causes mucosal irritation
    2. Start with once daily dosing and titrate to two to three times daily if needed
    3. Tolerance is directly related to iron concentration
      1. Start with normal concentration elemental iron
        1. Decrease to lower concentrations as needed
      2. Lower elemental iron concentration better tolerated
        1. Ferrous Gluconate
        2. More expensive iron preparations
        3. Consider 15 mg elemental iron liquid dissolved in orange juice
    4. Enteric coated Iron has decreased absorption
    5. Liquid formulations may be better tolerated
  2. Thick, green or black stools
  3. Metallic Taste
  4. Altered stool consistency (Constipation is most common, esp. in pregnancy)
  5. Abdominal cramping
  6. Hemochromatosis
    1. Prolonged, excessive Iron Supplementation
  • References
  1. Little (1999) Am Fam Physician 59(6):1598-604 [PubMed]