Iron Deficiency Treatment: 5 Pearls Segment

Core IM

In this episode of Core IM the team tackles understanding the nuances of oral and intravenous approaches, addressing special considerations regarding different formulations, managing patients with chronic inflammatory disorders, and recognizing associated complications and side effects of treatment.  Join them for Iron Deficiency Treatment: 5 Pearls Segment!

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Pearl 1: Spaced repetition from our Gray Matters Episode.

Iron deficiency diagnosis and workup

  • Iron deficiency diagnosis
  • Iron deficiency in chronic inflammatory disorders
    • Patients with chronic inflammation have elevated cytokines and acute-phase reactants.
      • As hepcidin levels rise, ferroportin degradation occurs in duodenal enterocytes.
      • Iron remains trapped within enterocytes and is also sequestered in macrophages.
    • A decrease in circulating iron leads to a lower saturation of the iron carrier protein, transferrin.
    • Thus, a low transferrin saturation (TSAT) (TSAT = (Serum Fe/TIBC) × 100) can aid with the diagnosis of ID in chronic inflammatory disorders.
    • Instead of using established diagnostic cut-offs for ID, cut-off parameters for ferritin and TSAT should be individualized for every patient, considering underlying inflammatory disorders and comorbidities.
      • TSAT <20% and ferritin 100-300 in inflammatory conditions (but this is largely from HF, CHF, CKD population)
    • A time-limited therapeutic trial of iron can help interpret diagnostic cut-offs in patients with active inflammation.
    • In a therapeutic trial of iron, a rise in hemoglobin > 1 g/dl over 2-4 weeks is highly sensitive for absolute ID.

Pearl 2: Oral vs IV iron repletion

  • Oral iron therapy is recommended for:
    • Patients who can tolerate oral iron
    • Patients without active bleeding
    • No evidence of severe symptomatic anemia
    • Patients without absorption disorders known to be unresponsive to oral iron
    • Patients who do not have chronic inflammatory disorders.

Pearl 3: Considerations with oral iron repletion

  • Oral Iron Formulations
    • In terms of efficacy, all compounds are essentially equivalent.
    • The most important component of a formulation is the amount of elemental iron.
      • Be aware of formulations that claim to have fewer side effects. They often have a lower amount of elemental iron and may not be as effective.
    • Common formulations include
        • Ferrous sulfate (65 mg  elemental iron per tablet-325 mg)
        • Ferrous gluconate (37.5 mg  elemental iron per tablet-325 mg)
        • Ferrous fumarate (106 mg elemental iron per tablet-325 mg).
    • Choose an affordable formulation.
  • Prescription and Absorption
    • Prescribe it initially once daily with an adequate bowel regimen.
      • If the patient has GI side effects, try iron every other day.
    • For better absorption, iron should be ingested
      • at least 30 minutes before a meal
      • 1 to 2 hours before taking additional medications.
      • Avoid taking iron with milk, calcium, caffeine, anti-acids, and tea.
        • Tailor patient instructions. Too many instructions may lead some patients to forget to take their iron all together.
    • Oral iron therapy should be continued for 6-12 months to replenish iron stores.
  • Effect of Vitamin C and Orange Juice on Oral Iron Absorption
    • A study evaluating the effect of Vitamin C supplementation, in 1994 on 25 women who were not anemic but had iron deficiency anemia, found a slightly increased serum ferritin in patients who received vitamin C supplementation.
    • In 2020, a JAMA RCT that included 440 adults with iron deficiency anemia showed no difference in the mean change in hemoglobin level after 2 weeks, for patients using oral iron supplementation alone versus a vitamin C-supplemented oral iron regimen.
    • Orange juice is often enriched with calcium, which can compete with iron absorption.
  • Post-treatment Labs
    • Post-treatment labs can be checked 6 months after initiating treatment.
    • Post-treatment target levels depend on how anemic the patient was to begin with but in general, we should target:
      •  Ferritin levels above 30-50
      •  TSAT levels above 20.

Pearl 4: Considerations with IV iron repletion

  • 1 infusion sitting:
    • Low-molecular-weight iron dextran
    • Ferumoxytol (faraheme)
      • can be 1-2 visits
    • Iron desiromaltose (monoferic)
  • 2 infusion sittings:
    • Ferric carboxymaltose comes in 2 different  presentations
  • 5 or more infusion sittings:
    • Ferrous gluconate and Iron sucrose
  • Formulations are similar in efficacy.
  • The side effect profile appears to be similar for all formulations, but further head-to-head comparisons are needed.
  • However, there is a higher incidence of hypophosphatemia, one of the features of the 6H syndrome, with ferric carboxymaltose.
    • 6H syndrome developes 1-2 weeks after infusion: Characterized by high FGF-23 levels, Hyperphosphaturia, Hypophospahtemia, Hypovitaminosis D, Hypocalcemia, and secondary Hyperparathyroidism
    • Ferric carboxymaltose induces FGF23 to increase, which leads to renal phosphate wasting, calcitriol deficiency, and secondary hyperparathyroidism.
    • Complications from the 6H syndrome include: osteomalacia, bone fractures, muscle weakness, and respiratory failure.
  • Dose calculation
    • The optimal IV iron dose can be estimated or calculated using the Ganzoni formula.
    • A practical approach is using 1 gram of iron without calculating the dose.
    • However, the Ganzoni formula is available online, easy to use, and can be helpful to avoid underdosing patients.
  • Post-treatment Laboratories:
    • Post-treatment labs should be checked 6 weeks after infusion.
    • Checking before 6 weeks can be associated with falsely high levels of ferritin.
      • Repeat doses are indicated if the ferritin level is not above 30-50 and TSAT above 20%.
    • During pregnancy, iron parameters should be checked every trimester and repeat doses should be given if patients remain iron deficient.

Pearl 5: Complications and side effects of IV iron

  • IV iron is a safe treatment option.
  • Severe reactions with IV iron are rare after the withdrawal of high-molecular-weight-dextran from the market.
    • Anaphylaxis in particular is estimated to occur in less than 1 per 250,000 administrations
  • Inpatient treatment considerations.
  • Fishbane reactions are minor and self-limited infusion reactions.
    • Described by Dr. Fishbane, a nephrologist.
    • Occurs in approximately 1 in 100 patients.
    • Characterized by flushing, arthralgias, myalgias, back and chest pain
    • Absence of anaphylactic symptoms.
      • Fishbane is not an allergic reaction. Not IgE mediated. The mechanism is suspected to be related to labile iron.
      • No increase in serum tryptase
    • Symptoms recover spontaneously and quickly after stopping the infusion
      • Infusion should be restarted at a slower rate.
      • Symptoms do not recur after restarting the infusion at a slower rate.
    • Do NOT administer EPINEPHRINE OR ANTIHISTAMINES (BENADRYL) as there is a high risk for circulatory collapse.



Shreya Trivedi, MD, ACP Member – Author
Nicholas Villano, MD – Host, Editor
Maria Fernandez, MD - Host/Editor
Jason Freed, MD – Guest Expert
Michael Auerbach, MD, FACP – Guest Expert*


Layla Van Doren, MD, MBA*
Jonathan Berry, MD

Layla Van Doren, MD, MBA
Consultant: Pharmacosmos Therapeutics, Inc., Sanofi and Genzyme US Companies
Other: Daiichi Sankyo, Inc, Global Blood Therapeutics, Inc., Pharmacosmos Therapeutics, Inc., Sobi, Inc

Michael Auerbach, MD, FACP
Grant/ Contract: Covis Pharma GmbH
Other: Pharmacosmos Therapeutics, Inc

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date: March 27, 2024

Expiration Date: March 26, 2027

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