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Not Just a Vitamin: Iron Toxicity and Management

Abstract Dietary supplements Iron Pill with FE Element

Take Home Points

  • Although the frequency has reduced significantly, iron toxicity still occurs and can be life-threatening
  • Severe toxicity is characterized by profuse vomiting and diarrhea, hypotension, acidosis, liver injury, and coma
  • It is important to note what iron product was ingested to determine the amount of elemental iron
  • Only a serum iron is useful in assessing acute toxicity. Ferritin and TIBC have no role in overdose.
  • Deferoxamine is indicated in severe iron toxicity, and whole bowel irrigation may be indicated if tablets can be seen on KUB.
  • Call the Utah Poison Control Center at 1-800-222-1222 at any time 24/7 for assistance in managing iron toxicity

Although iron ingestion is no longer the leading cause of poisoning deaths, it is not uncommon and can be a potentially fatal toxicologic emergency. In 2020, 4688 single cases of iron ingestion (as iron or iron salt formulations) were reported to US poison centers, with 2004 of those cases being in children under the age of 5 years. Also in 2020, there were about 8800 single cases of ingestion of a multivitamin formulation containing iron.1

Iron can cause direct injury to gastrointestinal mucosa, vasodilation, and impairment of cellular metabolism in the heart, liver, and central nervous system by disrupting oxidative phosphorylation and formation of free radicals.2 The toxicity of iron depends on the amount of elemental iron ingested, and elemental iron amounts vary between products. In addition, there are enteric-coated formulations that may delay absorption. The following iron salts are commonly found over-the-counter: ferrous sulfate (20% elemental iron), ferrous gluconate (12% elemental iron), and ferrous fumarate (33% elemental iron).3 As an example, a 325 mg tablet of ferrous sulfate contains 65 mg of elemental iron. Patients who ingest 20-60 mg/kg of elemental iron may develop nausea and vomiting but are at a low-risk for severe toxicity, while > 60 mg/kg is associated with a high-risk for severe toxicity and death.2

Iron toxicity is divided into 5 stages, although patients may not experience every stage and may skip stages as well. The first stage is within the first 6 hours after ingestion and consists of primarily GI symptoms including abdominal pain, nausea, vomiting, and diarrhea. Hematemesis and hematochezia may occur in more severe cases. In the second stage (6-24 hours post-ingestion), GI symptoms resolve but patients may have volume depletion and metabolic acidosis. In the third stage (6-72 hours post-ingestion) GI symptoms can return in addition to worsening metabolic acidosis and shock. In the fourth stage (12-96 hours), AST and ALT start to increase and may progress to liver failure. In the final stage (2-8 weeks post-ingestion) the patient may experience gastrointestinal scarring and obstruction.3

The most important lab value to be obtained is a serum iron concentration, ideally 4-6 hours post-ingestion to allow for absorption. Levels > 500 mcg/dL represents a higher risk of severe toxicity. Other important labs to order include renal function, electrolytes, complete blood count, coagulation studies, and hepatic panel.3 It is important to note that total iron binding capacity (TIBC) is not equivalent to a serum iron level and should not be used as a surrogate lab.4

All patients with a concern for iron toxicity should receive IV fluids, get a serum iron concentration 4-hours post ingestion, cardiac monitoring, and serial vital signs. A KUB can be obtained to assess for iron tablets and the potential for ongoing absorption. If tablets are seen, whole bowel irrigation can be considered also. There is no role for activated charcoal as it does not adsorb iron.

For patients who have a serum iron > 500 mcg/dL or > 350 mcg/dL AND persistent vomiting, acidosis, tachycardia, hypotension, lethargy, or tablets on KUB, deferoxamine is indicated. If a serum iron concentration is not available, it is appropriate to administer deferoxamine in severe toxicity (patients with signs of shock or metabolic acidosis in addition to lethargy, toxic appearance, hypotension, or persistent vomiting).4 Deferoxamine binds ferric ions in the blood to form ferrioxamine, which is renally excreted in urine. It does not remove iron bound to hemoglobin or transferrin, but rather the free iron that causes cell dysfunction.5 Deferoxamine should be infused at 5 mg/kg/hr and titrated up by 5 mg/kg/hr every 15 minutes to a goal rate of 15 mg/kg/hr. The patient should be reassessed after infusion of 1000 mg. If toxicity is ongoing, the generally recommended maximum dose is approximately 6-8 grams in 24 hours.6 Vitals, blood gas, chemistry panel, and iron levels should be obtained every 4 hours. A baseline urine sample in addition to urine samples every 4 hours can be obtained to measure urine color change, since deferoxamine can change urine to a pink, reddish, or orange color. Color changes, however, are not indicative of either efficacy or lack of efficacy of deferoxamine.5

Call the Utah Poison Control Center at 1-800-222-1222 at any time 24/7 for assistance in managing iron toxicity.

References

  1. Gummin DD, et al. 2020 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Tox. 2021; 59(12):1282-1501.
  2. Yuen HW, er al. Iron Toxicity. 2021 Jul 5. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK459224.
  3. O’Malley GF, et al. Iron Poisoning. 2020 Apr. MerckManuals.
  4. Nelson LS, et al. Goldfrank’s Toxicologic Emergencies, 11e. McGraw Hill; 2019. https://accessemergencymedicine.mhmedical.com/content.aspx?bookid=2569&sectionid=210256528
  5. Deferoxamine. In: Lexi-Drugs. Lexi-Comp, Inc. Updated 2022 Mar 8. Accessed 2022 Feb 12. https://online-lexi com.intermountain.proxy.liblynxgateway.com/lco/action/doc/retrieve/docid/patch_f/6699?cesid=6jzkbucC0Kq&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3Ddeferoxamine%26t%3Dname%26va%3Ddeferoxamine
Author: Ku’ulei Stuhr, PharmD, PGY2 Emergency Medicine Pharmacy Resident, Intermountain Medical Center