Tools for Practice


#284 Iron dosing frequency: Is less more or just less?


CLINICAL QUESTION
How does once daily iron dosing compare with dosing every second day or twice weekly?

BOTTOM LINE
Once daily dosing of iron yields similar or slightly better hemoglobin (~3 g/L) versus twice weekly or alternate day over ~3 months. Daily dosing increased ferritin similarly or up to 12 mg/L better. Adverse events (like abdominal pain) are reduced by up to 30% (absolute) with intermittent dosing. Research focused on females aged 14-22.


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EVIDENCE
5 randomized controlled trials (RCT) from Europe, India, and Iran, mean age 14-22 given 50-100 mg of elemental iron.
  • 40 females with ferritin ≤25µg/L, daily x14 days or alternating days x28 days.1
    • Hemoglobin started ~130g/L: both groups increased 4g/L.
    • Ferritin increased: 15µg/L versus 10µg/L (alternating day dosing), not quite statistically different (p=0.06).
  • 24 females with ferritin ≤15µg/L, daily or twice/week x90 days.2
    • Hemoglobin started ~124g/L: increased 6g/L versus 8g/L (twice/week dosing), not statistically different.
    • Ferritin increased: 16µg/L versus 4µg/L (twice/week dosing), statistically different.
  • 203 anemic females, daily or twice/week x12 weeks.3
    • Hemoglobin started ~91g/L: increased ~32g/L versus ~29g/L (twice/week dosing), statistically different.4
    • Abdominal pain (41% versus 5%), nausea (11% versus 1%), and vomiting (6% versus 0%) increased with daily dosing (statistically different, by authors).
  • 223 anemic females, daily x3 months or twice/week x1 year.5
    • Hemoglobin started ~97g/L: increased ~23g/L versus ~31g/L (twice/week dosing), statistics not reported.
    • Ferritin: both groups increased ~20 µg/L.
    • Total adverse events higher in once daily (39%) versus twice/week dosing (18%). Nausea, vomiting, and constipation most common.
    • All dropouts: 12% versus 4% (twice/weekly), not quite statistically different (p=0.053).
  • 204 females (49% anemic), daily or twice/week x3 months.6
    • Hemoglobin increased 7.4g/L versus 8.5g/L (twice/week), not statistically different.4
    • Ferritin improved more with daily iron (numbers not provided).
Context:
  • Overall limitations include lack of blinding,1-3,5,6 imbalanced follow-up duration between study groups,1,5 poor randomization,1,5 and short follow-up.1
  • Trials demonstrate a trade-off with intermittent iron (every second day or twice/week): leading to slightly lower improvement in hemoglobin (≤3 g/L) and ferritin (12 µg/L) but less adverse events that may promote adherence.
February 22, 2021

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Author(s):

  • G. Michael Allan MD CCFP
  • Holly Lee MD FRCPC
  • Man-Chiu Poon MD FRCPC

1. Stoffel NU, Cercamondi CI, Brittenham G, et al. Lancet Haematol. 2017; 4(11):e524- e533.

2. Ruivard M, Feillet-Coudray C, Rambeau M, et al. Clin Biochem. 2006; 39:700-7.

3. Shobha S, Sharada D. Indian Pediatr. 2003; 40:1186-90.

4. Fernández-Gaxiola AC, De-Regil LM. Cochrane Database Syst Rev. 2019; 1:CD009218.

5. Gupta A, Parashar A, Thakur A, et al. Int J Prev Med. 2014; 5:1475-9.

6. Kianfar H, Kimiagar M, Ghaffarpour M. Int J Vitam Nutr Res 2000; 70:172-7

Authors do not have any conflicts of interest to declare.