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Daily versus alternate day oral iron therapy in iron deficiency anemia: a systematic review

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Daily administration of oral iron is considered the current treatment standard for treating iron deficiency anemia due to availability and reduced cost compared to intravenous iron therapy. But adverse effects like epigastric pain, heartburn, and constipation reduce compliance to daily oral iron. There is scanty evidence regarding compliance and efficacy with alternate-day iron therapy. As per our knowledge, this is the first systematic review to compare daily with alternate-day oral iron therapy. Six electronic databases including PubMed and EMBASE were searched for randomized controlled trials, quasi-experimental studies published between January 2000 to March 2023 that compared daily with alternate day iron therapy in individuals diagnosed with iron deficiency anemia. The primary outcome analyzed was a change in hemoglobin. The other hematological parameters were assessed as secondary outcomes. Risk of bias was assessed regarding randomization process, deviation from intended intervention, missing outcome data, measurement of the outcome, and selection of the reported result. Out of the 9 full-text articles, 2 were not included as one was an ongoing trial and the second one had a different study design. The reviewed trials involved 594 participants, and the study participants ranged from 19 to 200. The mean age of the participants in the reported trials was 21 ± 2 to 49 ± 16 years. There is no significant increase in hemoglobin level and also the iron indices namely ferritin, hepcidin, total iron binding capacity, and reticulocyte count between daily and alternate-day dosing of iron. However, the frequency of adverse effects especially nausea, metallic taste, and altered bowel habits are reduced with alternate-day dosing. Oral iron given daily or on alternate days did not have a significant difference in the hemoglobin levels though iron absorption may be affected in the initial few days.

Trial registration: The review protocol was registered with PROSPERO (Prospero2023CRD42023393095).

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No grant was received from any funding agency either from government or private sector for the conduct of the study.

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SK and VN conceived and designed the study. SK and EM developed the search strategy and did the literature search. SK, VN, RS, SH, and EM conducted the data extraction. SK, VN, and SH conducted the quality assessment of the selected studies. SK and VN wrote the initial draft of the manuscript. SK, VN, AB, EM, RS, and SH did the writing—review and editing. AB has provided valuable comments and clinical inputs to the manuscript. All authors have helped in drafting and approving the final version of the manuscript. The authors confirm that no paper mill and artificial intelligence was used.

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Correspondence to Veena Nayak.

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Kamath, S., Parveen, R.S., Hegde, S. et al. Daily versus alternate day oral iron therapy in iron deficiency anemia: a systematic review. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2701–2714 (2024).

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