British Columbia Drug and Poison Information Centre (BC DPIC)

By Shelina Rayani, B.Sc.(Pharm.), R.Ph., CSPI, Drug and Poison Information Pharmacist, BC Drug and Poison Information Centre
Reviewed by C. Laird Birmingham, MD, M.H.Sc., FRCPC

BACKGROUND

Iron is an essential mineral required for the synthesis of hemoglobin, cytochromes and myoglobin. Seventy percent of total body iron is present in hemoglobin, 25% in ferritin, 5% in myoglobin and < 0.5% in tissue enzymes and plasma transferrin.^1,2

Dietary iron is either "heme" iron from red meat, fish and poultry, which is well absorbed (15-35%) or "non-heme" iron from fruits, vegetables, cereals and dairy, which is poorly absorbed (2-5%).⁴ Supplements may have either form of iron.

Normally, 1 to 2 mg of iron is absorbed by and lost from the body daily.¹ Ferrous iron is absorbed in the small intestine, oxidized to ferric iron and bound to ferritin.² Iron is released from ferritin into the plasma where it binds to transferrin.² Transferrin transports the ferric iron necessary for erythropoiesis in the bone marrow.² Iron is not actively excreted. Approximately 1 mg is lost daily from the intestine, sweat and urine.^1-3 Menstruating women lose another 1 mg of iron daily.³

DEFICIENCY

Iron deficiency can cause anemia, developmental delay, cognitive and intellectual impairment, adverse pregnancy outcomes, impaired immune function and hair loss.^4,5 Supplements are used to prevent and treat deficiency, and during pregnancy when requirements are higher. General dosing guidelines are listed in Table I.^4,6 Iron is available in various forms, each providing a different elemental iron content and absorption profile (Table II). Dosages should be calculated based on the elemental iron content.

A hematology profile should be measured once after 2 to 4 weeks of treatment, then as needed.⁴ The hemoglobin usually normalizes within 2 to 4 months with appropriate dosing, treatment of concurrent deficiencies and correction of the underlying cause.⁴ Continuing therapy for 4 to 6 months after the hemoglobin normalizes is necessary to fully replete iron stores.⁴ A low maintenance dose and dietary modification may be required.⁴

• Consider both adequate dosage and patient tolerance when choosing a preparation
• Ingest in upright position with plenty of fluids and avoid lying down for 10 minutes
• To maximize absorption:
  • Take on an empty stomach
  • Divide doses over the day
  • Take with orange juice or Vitamin C
  • Avoid antacids, calcium, high fiber foods, milk and caffeinated beverages within 2 hours

• Oral supplements may cause:
  • Nausea   • Dyspepsia   • Diarrhea
  • Vomiting   • Constipation   • Dark stools

• With the exception of dark stools, side effects usually subside with continued therapy
• To minimize side effects:
  • Initiate low dose and increase over 4 to 5 days
  • Try iron salt with less elemental iron
  • Take with food

• Liquid preparations may stain teeth - mix with juice/water and drink through a straw. Brushing teeth with sodium bicarbonate removes existing stains.
• Store supplements safely! The tablet's bright colouring may attract children.

TOXICITY
When transferrin's binding capacity is exceeded, excess iron circulates in its free form.² Iron in this state readily accepts and donates electrons, causing iron to alternate between ferric (Fe2+) and ferrous (Fe3+) forms.¹ This can catalyze production of hydroxyl radicals in tissues causing cellular injury and organ failure.^1,2,13

Symptoms of Iron toxicity begin a few hours post ingestion.¹³ Serious toxicity can include vomiting, gastrointestinal bleeding, hypotension, metabolic acidosis, shock and hepatic failure.¹³ Death can occur within 48 to 96 hours in severe cases.¹³ An acute ingestion of < 40 mg/kg elemental iron is unlikely to produce serious toxicity.¹³ However, an acute ingestion of > 40 mg/kg should be assessed at a hospital emergency room.¹³

*There are a myriad of diverse iron formulations. These are listed for information purposes. One preparation is not preferred over another. Patient tolerance should be the guide.

REFERENCES

1. Andrews NC. Disorders of Iron Metabolism. NEJM. 1999 Dec 23;341(26):1986-1995.
2. Lacouture P. Iron. Clinical Toxicology Review. 1979 Jul;1 (10):1-4.
3. Alldredge BK, Corelli RL, Ernst ME, Guglielmo BJ, Jacobson PA, Kradjan WA et al. Koda-Kimble & Young's Applied Therapeutics - The Clinical Use of Drugs. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2013.
4. Guidelines & Protocols Advisory Committee (GPAC). Iron Deficiency - Investigation and Management [Internet]. 2010 June 15. Available from: http://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/iron-deficiency.
5. Abdulla K, Zlotkin S, Parkin P, Grenier D. Iron-deficiency anemia in children [Internet]. Canadian Paediatric Surveillance Program Resources. 2011 January. Available from: http://www.cpsp.cps.ca/uploads/publications/RA-iron-deficiency-anemia.pdf
6. Dipchand A, Friedman J, Bismilla Z, Gupta S, Lam C. The Hospital for Sick Children - Handbook of Pediatrics. 11th ed. Toronto: Elsevier Canada; 2009.
7. Tom W. Comparison of Oral Iron Supplements. Pharmacist's Letter/Prescriber's Letter 2008;24(8):240811
8. Ibrahim D. Oral Iron Supplements: A Review Feb 14, 2003. Saskatchewan Drug Information Service: University of Saskatchewan 2007. 3p.
9. Wiebe A, Ricci P, Geall B, Gross L, Dumont Z. Iron Management: Chronic Kidney Disease - Iron Deficiency Anemia (CKD-IDA) [Internet]. Saskatoon: Saskatoon Health Region; 2015 Jul. Available from: http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-anemia-iron-products.pdf
10. Short MW, Domagalski JE. Iron Deficiency Anemia: Evaluation and Management. Am Fam Physician 2013 Jan 15;87(2):98-104.
11. Schrier SL, Auerbach M, Mentzer WC, Tirnauer JS. Treatment of the adult with iron deficiency anemia. In: UpToDate, Post, TW (Ed). UpToDate, Waltham, MA, 2015.
12. MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US); [updated 2005 Aug 12]. Taking iron supplements; [updated 2013 May 13; cited 2015 Nov 18]; [about 2p.]. Available from: https://www.nlm.nih.gov/medlineplus/ency/article/007478.htm
13. Poison Management Manual. Vancouver: BC Drug and Poison Information Centre; 2015 March. Iron [3p].
14. Licensed Natural Health Products Database [Internet] 2015 [cited 2015 Nov 19]. Available from: http://www.hc-sc.gc.ca/dhp-mps/prodnatur/applications/licen-prod/lnhpd-bdpsnh-eng.php.
15. BC Pharmacare Low Cost Alternative and Reference Drug Program [Internet] 2015. [updated 2015 Nov 5; cited 2015 Nov 19]. Available from: http://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/pharmacare/pharmacies/low-cost-alternative-lca-and-reference-drug-program-rdp-data-files
16. Proferrin Heme Iron Polypeptide [Internet] 2015 [cited 2015 Nov 19]. Available from: http://proferrin.ca/
17. Feramax Oral Iron Supplement [Internet] 2013 [cited 2015 Nov 19]. Available from: http://www.feramax.com/feramax150patient/feramax150patient-faq.html
18. Verbal communication with Selina, Customer Service, BioSyent Pharma Inc. re: Feramax powder dosing in adults 2015 Nov 17.
19. BC College of Pharmacists Drug Schedules [Internet] 2015 [updated 2015 Oct; cited 2015 Nov 19]. Available from: http://www.bclaws.ca/civix/document/id/complete/statreg/9_98

A version of this article was published in BCPhA's The Tablet. 2016; 25(1): 8-9.