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
- The absence of iron stores in the bone marrow remains the gold standard for diagnosis; however, its high invasiveness renders it less favorable.
- Iron deficiency (ID) is the most common cause of but can also present with
- Ferritin is the most
- levels are the hallmark of absolute ID.
- As a rule of thumb, a ferritin cut-off can be used to diagnose ID in a patient without inflammation.
- Iron deficiency in chronic inflammatory disorders
- Patients with chronic inflammation have
- 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 disorders.
- Instead of using established diagnostic cut-offs for ID, cut-off parameters for ferritin and TSAT should be for every patient, considering underlying inflammatory disorders and comorbidities.
- and ferritin 100-300 in inflammatory conditions (but this is largely from HF, CHF, CKD population)
- Patients with chronic inflammation have
-
- A time-limited therapeutic trial of iron can help interpret diagnostic cut-offs in patients with active inflammation.
- In a , a rise in over 2-4 weeks is highly sensitive for absolute ID.
Pearl 2: Oral vs IV iron repletion
- 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.
- is recommended for:
- Patients who were unable to tolerate oral iron despite adequate management of side effects
- Patients with active bleeding or blood losses
- Patients with
- Patients with limited ability to absorb oral iron
- Patients with , and rheumatologic disorders, among others.
- Conditions in which the administration of oral iron may be such as .
- of
Pearl 3: Considerations with oral iron repletion
- Oral Iron Formulations
- In terms of efficacy, all compounds are .
- 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
-
- 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 , 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.
- Prescribe it initially once daily with an adequate bowel regimen.
- Effect of Vitamin C and Orange Juice on Oral Iron Absorption
- A study evaluating the 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 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
- 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
- : # of Infusion Sitting to get 1g of iron
- 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 .
- The side effect profile appears to be similar for all formulations, but further comparisons are needed.
- However, there is a higher incidence of , one of the features of the 6H syndrome, with ferric .
- developes 1-2 weeks after infusion: Characterized by high FGF-23 levels, Hyperphosphaturia, Hypophospahtemia, Hypovitaminosis D, Hypocalcemia, and secondary Hyperparathyroidism
- Ferric carboxymaltose induces to increase, which leads to renal phosphate wasting, calcitriol deficiency, and secondary hyperparathyroidism.
- 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 is using 1 gram of iron without calculating the dose.
- However, the Ganzoni formula is available , easy to use, and can be helpful to avoid underdosing patients.
- Post-treatment Laboratories:
- should be checked after infusion.
- Checking before 6 weeks can be associated with 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 and repeat doses should be given if patients remain iron deficient.
Pearl 5: Complications and side effects of IV iron
- IV iron is a 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 administrations
- Inpatient treatment considerations.
- Recent evidence has demonstrated IV iron is and does not confer a higher risk of infections. It can be administered in patients with
- Avoid IV iron in patients with active .
- are minor and self-limited infusion reactions.
- Described by Dr. Fishbane, a nephrologist.
- Occurs in approximately 1 in 100 patients.
- 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
- 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 (BENADRYL) as there is a high risk for circulatory collapse.
Contributors
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*
Reviewers
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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