Iron dosing frequency (2024)

Clinical question

How does once-daily (QD) iron dosing compare with dosing every second day (QOD) or twice weekly (BIW)?

Bottom line

Once-daily dosing of iron results in similar or slightly better hemoglobin (Hb) levels (about 3 g/L) than QOD or BIW dosing during a 3-month period. Daily dosing increases serum ferritin levels similarly or by up to 12 µg/L better. Intermittent dosing reduces adverse events (like abdominal pain) by up to 30% (absolute).

Evidence

Five RCTs from Europe, India, and Iran (mean age 14-22; 50-100 mg of elemental iron) found the following:

• In 40 females taking ferritin (≤ 25 µg/L) QD for 14 days or for 28 days QOD,¹ base Hb levels of both groups were around 130 g/L and increased by 4 g/L. Serum ferritin levels increased by 15 µg/L (QD) and by 10 µg/L (QOD); not statistically different (P = .06).

• In 24 females taking ferritin (≤ 15 µg/L) either QD or BIW for 90 days,² Hb levels increased from about 124 g/L by 6 g/L (QD) and by 8 g/L (BIW); not statistically different. Serum ferritin levels increased by 16 µg/L (QD) versus 4 µg/L (BIW); statistically different.

• In 203 females with anemia taking iron either QD or BIW for 12 weeks,³ Hb levels increased approximately from 91 g/L by 32 g/L (QD) and by 29 g/L (BIW); statistically different.⁴

  - Abdominal pain (41% vs 5%), nausea (11% vs 1%), and vomiting (6% vs 0%) increased with QD dosing; statistically different, according to authors.

• In 223 females with anemia treated with iron and folic acid either QD for 3 months or BIW for 1 year,⁵ Hb levels increased approximately from 97 g/L by 23 g/L (QD) and by 31 g/L (BIW); statistics not reported. Serum ferritin levels in both groups increased by about 20 µg/L.

  - Adverse events: 39% versus 18% (BIW). Nausea, vomiting, and constipation were the most common.

  - All dropouts: 12% versus 4% (BIW); not statistically different (P = .053).

• In 204 females (49% with anemia) given 50 mg of iron either QD or BIW for 3 months,⁶ Hb levels increased 7.4 g/L (QD) versus 8.5 g/L (BIW); not statistically different.⁴ Serum ferritin levels increased more with daily iron dosing (numbers not provided).

Context

• Limitations: lack of blinding,^1-3,5,6 short¹ and imbalanced follow-up between groups,^1,5 and poor randomization.^1,5

• Trials show a trade-off with intermittent iron (QOD or BIW), leading to slightly lower improvement in Hb (≤ 3 g/L) and ferritin (12 µg/L) levels, but have fewer adverse events, which might promote adherence.

Implementation

A main barrier to effective iron replacement is nonadherence (up to 70% cases⁷) due to dose-dependent gastrointestinal side effects. Less frequent dosing improves tolerability,^1,3,5 but therapy duration might be longer than with QD dosing owing to lower Hb level increases. Ferrous gluconate or sulfate versus fumarate have been suggested for improved adherence.^8,9 Consolidation therapy for 3 months is recommended upon iron deficiency correction to replenish stores.¹⁰ Optimal iron replacement formulation, frequency, and duration should be discussed with patients to optimize treatment efficacy and adherence.

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.

• This article is eligible for Mainpro+ certified Self-Learning credits. To earn credits, go to www.cfp.ca and click on the Mainpro+ link.

• La traduction en français de cet article se trouve à www.cfp.ca dans la table des matières du numéro de juin 2021 à la page e142.

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