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#234 Iron-ing Out the Wrinkles in Anemia Management

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

Newer iron formulations appear inferior to older ferrous salts.  Ferrous salts improve hemoglobin up to 10-20g/L more and perhaps one in five more attaining IDA resolution at 3 months.  Evidence that newer formulations have less adverse effects is inconsistent.  

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Randomized controlled trials. Differences statistically significant unless indicated. 
  • General population adults: 
    • 80 patients (92% female, mean age 39):1 iron polysaccharide (Niferex™) versus ferrous fumarate, both ~150mg/day elemental iron. After 12 weeks: 
      • Ferrous fumarate improved hemoglobin (28.4g/L) more than iron polysaccharide (6g/L), and had better serum ferritin, mean corpuscular volume, and transferrin saturation but more nausea (31% versus 3%). 
    • 80 children (mean age 23 months):2 Iron polysaccharide (NovaFerrum™) versus ferrous sulfate, both 3mg/kg/day elemental iron. 
      • At 12 weeks, ferrous sulphate improved hemoglobin more (10g/L), resolved IDA (29% vs 6%, Number Needed to Treat=5), caused less diarrhea (35% versus 58%). 
    • Smaller trials of adults (n=43)3 and premature infants (n=32)4: iron polysaccharide and ferrous salts were no different in hemoglobin improvement after 4-6 weeks. 
  • Subgroups: 
    • Dialysis patients: At 6 months, ferrous salts no different from newer formulations on transferrin saturation5,6 or proportion of iron-replete patients.5 
      • Ferritin ~(160µg/L) better with ferrous sulfate than heme iron (Proferrin ES™).5 
    • Post-gastric bypass (n=14):7 Ferrous sulfate improved hemoglobin 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) no different from higher doses ferrous fumarate alone in achieving anemia outcomes; 8,9 ferrous fumarate alone caused more constipation (35% versus 14%).8 
  • Multiple limitations including underpowered,2,4,6-9 multiple outcomes,1-9 non-intention-to-treat.1,2,5 
  • Approximate costs/month for 100mg elemental iron/day10: ferrous fumarate/sulphate (generics $5-10), ferrous fumarate (Palafer™ $35), iron polysaccharide complexes (Feramax™ $35). 
  • To reduce iron-related gastrointestinal upset: lower dose11; use another ferrous salt (incidence of adverse effects: ferrous gluconate 30%, sulfate 32%, fumarate 47%);12 alternate day dosing.13 

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  • Samantha Moe PharmD
  • G. Michael Allan MD CCFP

1. Liu TC, Lin SF, Chang CS, et al. Int J Hematology. 2004;80:416-20.

2. Piccinni L, Ricciotti M. Panminerva Medica. 1982 24:213-20.

3. Powers JM, Buchanan GR, Adix L, et al. JAMA. 2017; 317:2297-304.

4. Naude S, Clijsen S, Naulaers G, et al. J Clin Pharmcol. 2000; 40:1447-51.

5. Barraclough KA, Brown F, Hawley CM, et al. Nephrol Dial Transpl. 2012; 27:4146-53.

6. Wingard RL, Parker RA, Ismail N, Hakim RM. Am J Kid Dis. 1995;433-9.

7. Mischler RA, Armah SM, Craig BA, et al. Obes Surg. 2018; 28:369-77.

8. Frykman E, Bystrom M, Jansson U, et al. J Lab Clin Med. 1994; 123:561-4.

9. Eskeland B, Malterud K, Ulvik RJ, et al. Acta Obstetricia et Gynecologica Scandinavica 1997; 76: 822-8.

10. Kolber MR, Lee J, Allan GM, et al. Price Comparison of Commonly Prescribed Pharmaceuticals in Alberta 2018. Available at

11. Lindblad AJ, Cotton C, Allan GM. Can Fam Physician. 2015; 61:159.

12. Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S, et al. Curr Med Res Opin. 2013; 29:291-303.

13. Stoffel NU, Cercamondi C, Brittenham G, et al. Lancet Hematol. 2017; 4:E524-33.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.