OtherPractice

Newer iron supplements for anemia

Samantha Moe, Allan K. Grill and G. Michael Allan
Canadian Family Physician August 2019, 65 (8) 556;

Clinical question

Are newer oral iron formulations (iron polysaccharide complex or heme iron polypeptide) better than ferrous salts for iron deficiency anemia (IDA)?

Bottom line

Newer iron formulations appear to be inferior. Ferrous salts improve hemoglobin (Hb) levels by up to 10 to 20 g/L more, with IDA resolution in perhaps 1 in 5 more patients at 3 months. Evidence that newer formulations have fewer adverse effects is inconsistent.

Evidence

The following evidence is from RCTs. Differences are statistically significant unless otherwise indicated.

  • Iron polysaccharide (Niferex) compared with ferrous fumarate (both about 150 mg/d elemental iron) in 80 patients (92% female, mean age 39)1: After 12 weeks, ferrous fumarate improved Hb levels (28.4 g/L) more than iron polysaccharide (6 g/L) did, and patients had better serum ferritin levels, mean corpuscular volume, and transferrin saturation but more nausea (31% vs 3%).

  • Iron polysaccharide (NovaFerrum) compared with ferrous sulfate (both 3 mg/kg/d elemental iron) in 80 children (mean age 23 months)2: After 12 weeks, ferrous sulfate improved Hb levels more (10 g/L), resolved IDA more often (29% vs 6%, number need to treat of 5), and caused less diarrhea (35% vs 58%).

  • Smaller trials of adults (n = 43)3 and premature infants (n = 32)4 comparing iron polysaccharide and ferrous salts found no differences in Hb improvement at 4 to 6 weeks.

  • Dialysis patients: At 6 months, ferrous salts were no different from newer formulations in transferrin saturation5,6 or proportion of iron-replete patients.5 Ferritin levels (about 160 µg/L) were better with ferrous sulfate than with heme iron (Proferrin ES).5

  • Post–gastric bypass (n = 14)7: Ferrous sulfate improved Hb levels after 8 weeks, but heme iron (Proferrin ES) did not.

  • Blood donors (n = 97)8 and pregnant patients (n = 90)9: Heme iron with ferrous fumarate (Hemofer) was no different from higher-dose ferrous fumarate alone8,9; ferrous fumarate alone caused more constipation (35% vs 14%).8

Context

  • Trials had multiple limitations: underpowered,2,4,6–9 multiple outcomes,1–9 and not intention-to-treat.1,2,5

  • Approximate costs per month for 100 mg of elemental iron per day10: ferrous fumarate or sulfate (generics, $5 to $10), ferrous fumarate (Palafer, $35), and iron polysaccharide complexes (Feramax, $35).

Implementation

The cause of IDA should be determined. Treatment with ferrous salts (100 to 200 mg/d elemental iron)11 might take up to 3 months to normalize Hb levels and replenish iron stores.12 Newer formulations are more expensive and do not appear to provide additional benefit. Gastrointestinal side effects are common; compliance might improve with lower doses, alternate-day dosing, or selecting ferrous gluconate or sulfate over fumarate.13 In patients who fail oral therapy or with poor oral absorption (eg, inflammatory bowel disease), intravenous iron can be considered.12,14

Notes

Tools for Practice articles in Canadian Family Physician are adapted from articles published on the Alberta College of Family Physicians (ACFP) website, summarizing medical evidence with a focus on topical issues and practice-modifying information. The ACFP summaries and the series in Canadian Family Physician are coordinated by Dr G. Michael Allan, and the summaries are co-authored by at least 1 practising family physician and are peer reviewed. Feedback is welcome and can be sent to toolsforpractice{at}cfpc.ca. Archived articles are available on the ACFP website: www.acfp.ca.

Footnotes

  • Competing interests

    None declared

  • The opinions expressed in Tools for Practice articles are those of the authors and do not necessarily mirror the perspective and policy of the Alberta College of Family Physicians.

References

  1. 1.↵
    1. Liu TC,
    2. Lin SF,
    3. Chang CS,
    4. Yang WC,
    5. Chen TP
    . Comparison of a combination ferrous fumarate product and a polysaccharide iron complex as oral treatments of iron deficiency anemia: a Taiwanese study. Int J Hematology 2004;80(5):416-20.
    OpenUrl
  2. 2.↵
    1. Piccinni L,
    2. Ricciotti M
    . Therapeutic effectiveness of an iron-polysaccharide complex in comparison with iron fumarate in the treatment of iron deficiency anemias. Panminerva Med 1982;24(3):213-20.
    OpenUrlPubMed
  3. 3.↵
    1. Powers JM,
    2. Buchanan GR,
    3. Adix L,
    4. Zhang S,
    5. Gao A,
    6. McCavit TL
    . Effect of low-dose ferrous sulfate vs iron polysaccharide complex on hemoglobin concentration in young children with nutritional iron-deficiency anemia: a randomized trial. JAMA 2017;317(22):2297-304.
    OpenUrlCrossRefPubMed
  4. 4.↵
    1. Naude S,
    2. Clijsen S,
    3. Naulaers G,
    4. Daniels H,
    5. Vanhole C,
    6. Devlieger H
    . Iron supplementation in preterm infants: a study comparing the effect and tolerance of a Fe2+ and a nonionic FeIII compound. J Clin Pharmcol 2000;40(12 Pt 2):1447-51.
    OpenUrl
  5. 5.↵
    1. Barraclough KA,
    2. Brown F,
    3. Hawley CM,
    4. Leary D,
    5. Noble E,
    6. Campbell SB,
    7. et al
    . A randomized controlled trial of oral heme iron polypeptide versus oral iron supplementation for the treatment of anaemia in peritoneal dialysis patients: HEMATOCRIT trial. Nephrol Dial Transpl 2012;27(11):4146-53. Epub 2012 Sep 7.
    OpenUrlCrossRefPubMed
  6. 6.↵
    1. Wingard RL,
    2. Parker RA,
    3. Ismail N,
    4. Hakim RM
    . Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin. Am J Kid Dis 1995;25(3):433-9.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Mischler RA,
    2. Armah SM,
    3. Craig BA,
    4. Rosen AD,
    5. Banerjee A,
    6. Selzer DJ,
    7. et al
    . Comparison of oral iron supplement formulations for normalization of iron status following Roux-EN-y gastric bypass surgery: a randomized trial. Obes Surg 2018;28(2):369-77.
    OpenUrl
  8. 8.↵
    1. Frykman E,
    2. Bystrom M,
    3. Jansson U,
    4. Edberg A,
    5. Hansen T
    . Side effects or iron supplements in blood donors: superior tolerance of heme iron. J Lab Clin Med 1994;123(4):561-4.
    OpenUrlPubMed
  9. 9.↵
    1. Eskeland B,
    2. Malterud K,
    3. Ulvik RJ,
    4. Hunskaar S
    . Iron supplementation in pregnancy: is less enough? A randomized, placebo controlled trial of low dose iron supplementation with and without heme iron. Acta Obstet Gynecol Scand 1997;76(9):822-8.
    OpenUrlCrossRefPubMed
  10. 10.↵
    1. Kolber MR,
    2. Lee J,
    3. Korownyk C,
    4. Allan GM,
    5. Nickonchuk T
    . Price comparison of commonly prescribed pharmaceuticals in Alberta 2018. Edmonton, AB: Alberta College of Family Physicians; 2018. Available from: https://acfp.ca/wp-content/uploads/2018/03/ACFPPricingDoc2018.pdf. Accessed 2019 May 25.
  11. 11.↵
    1. Towards Optimized Practice.
    Iron deficiency anemia (IDA). Clinical practice guideline. Edmonton, AB: Towards Optimized Practice; 2018. Available from: www.topalbertadoctors.org/download/2256/IDA%20CPG.pdf?_20190405124948. Accessed 2019 Feb 3.
  12. 12.↵
    1. Goddard A,
    2. James M,
    3. McIntyre A,
    4. Scott B
    . Guidelines for the management of iron deficiency anemia. Gut 2011;60(10):1309-16. Epub 2011 May 11.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Cancelo-Hidalgo MJ,
    2. Castelo-Branco C,
    3. Palacios S,
    4. Haya-Palazuelos J,
    5. Ciria-Recasens M,
    6. Manasanch J,
    7. et al
    . Tolerability of different oral iron supplements: a systematic review. Curr Med Res Opin 2013;29(4):291-303. Epub 2013 Feb 6.
    OpenUrlCrossRefPubMed
  14. 14.↵
    1. Johnson-Wimbley TD,
    2. Graham DY
    . Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol 2011;4(3):177-84.
    OpenUrlCrossRefPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Respond to this article
Newer iron supplements for anemia
Samantha Moe, Allan K. Grill, G. Michael Allan
Canadian Family Physician Aug 2019, 65 (8) 556;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo

Jump to section