View source for Iron supplement

{{Short description|Iron formulation used to prevent or treat iron deficiency anemia}}
{{See also|Ferrous sulfate}}
{{Use dmy dates|date=October 2024}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image             = Dr Williams' 'Pink Pills', London, England, 1850-1920 Wellcome L0058211.jpg
| alt               = 
| caption           = Iron supplement from the late 19th and early 20th century

<!-- Clinical data -->
| pronounce         =
| tradename         = Feosol, Feostat, Feratab, others
| Drugs.com         = {{ubl
  | {{drugs.com|monograph|iron-preparations-oral}}
  | {{drugs.com|monograph|iron-dextran}}
  }}
| MedlinePlus       = 
| DailyMedID        = Iron
| pregnancy_AU      = B3
| pregnancy_AU_comment = 
| pregnancy_category= 
| routes_of_administration = [[By mouth]], [[intravenous]], [[intramuscular]]
| class             = 
| ATC_prefix        = B03
| ATC_suffix        = A
| ATC_supplemental  = 

<!-- Legal status -->
| legal_AU          = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment  = 
| legal_BR          = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment  = 
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Ferinject Product information | website=[[Health Canada]] | date=11 March 2024 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=103479 | access-date=21 June 2024}}</ref><ref>{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=[[Health Canada]] | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}</ref><ref>{{cite web | title=Summary Basis of Decision for Ferinject | website=[[Health Canada]] | date=10 September 2024 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1725979957573 | access-date=12 October 2024}}</ref><ref>{{cite web | title=Notice: Multiple additions to the Prescription Drug List (PDL) [2024-10-18] | website=[[Health Canada]] | date=18 October 2024 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/prescription-drug-list/notices-changes/multiple-additions-2024-10-18.html | access-date=25 October 2024}}</ref>
| legal_DE          = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment  = 
| legal_NZ          = <!-- Class A, B, C -->
| legal_NZ_comment  = 
| legal_UK          = [[OTC drug|OTC]] / POM
| legal_UK_comment  = <ref>{{cite web | title=About ferrous fumarate | website=[[NHS.UK]] | date=8 August 2022 | url=https://www.nhs.uk/medicines/ferrous-fumarate/about-ferrous-fumarate/#:~:text=About%20ferrous%20fumarate%20Brand%20names,and%20to%20buy%20from%20pharmacies. | access-date=22 November 2024}}</ref><ref>{{cite web | title=About ferrous sulfate | website=[[NHS.UK]] | date=9 February 2023 | url=https://www.nhs.uk/medicines/ferrous-fumarate/about-ferrous-fumarate/#:~:text=About%20ferrous%20fumarate%20Brand%20names,and%20to%20buy%20from%20pharmacies. | access-date=22 November 2024}}</ref><ref name="Cosmofer SmPC" /><ref name="Ferinject SmPC" />
| legal_US = OTC
| legal_US_comment  = /&nbsp;Rx-only<ref name="Injectafer FDA label" /><ref name="Drug Approval Package: Accrufer" />
| legal_EU          = 
| legal_EU_comment  = 
| legal_UN          = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment  = 
| legal_status      = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability   = 
| protein_bound     = 
| metabolism        = 
| metabolites       = 
| onset             = 
| elimination_half-life = 
| duration_of_action = 
| excretion         = 

<!-- Identifiers -->
| CAS_number        = 1332-96-3
| CAS_supplemental  = 
| PubChem           = 
| IUPHAR_ligand     = 
| DrugBank          = 
| ChemSpiderID      = None
| UNII              = 
| KEGG              = 
| ChEBI             = 
| ChEMBL            = 
| NIAID_ChemDB      = 
| PDB_ligand        = 
| synonyms          = Iron pills, iron salts, ferrous salts, ferric salts

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| IUPAC_name        = 
| chemical_formula_ref =
| chemical_formula  = 
| C= | H= | Ag= | Al= | As= | Au= | B= | Bi= | Br= | Ca= | Cl= | Co= | F= | Fe= | Gd= | I= 
| K= | Li= | Mg= | Mn= | N= | Na= | O= | P= | Pt= | S= | Sb= | Se= | Sr= | Tc= | Zn= | charge= 
| molecular_weight  = 
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}}

<!-- Definition and medical uses -->
'''Iron supplements''', also known as '''iron salts''' and '''iron pills''', are a number of [[iron]] formulations used to treat and prevent [[iron deficiency]] including [[iron-deficiency anemia]].<ref name=Ric2015>{{cite book| vauthors = Hamilton R |title=Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition|date=2015|publisher=Jones & Bartlett Learning|isbn=9781284057560|page=217}}</ref><ref name=BNF69>{{cite book|title=British National Formulary: BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=660–664|edition=69}}</ref> For prevention they are only recommended in those with [[malabsorption|poor absorption]], [[heavy menstrual periods]], [[pregnancy]], [[hemodialysis]], or a diet low in iron.<ref name=BNF69/><ref name=WHO2008/> Prevention may also be used in [[low birth weight]] babies.<ref name=BNF69/> They are taken by mouth, [[injection into a vein]], or [[injection into a muscle]].<ref name=BNF69/> While benefits may be seen in days, up to two months may be required until iron levels return to normal.<ref name=AHFS2017/>

<!-- Side effects and mechanism -->
Common side effects include [[constipation]], abdominal pain, dark stools, and [[diarrhea]].<ref name=AHFS2017>{{cite web|title=Iron Preparations, Oral|url=https://www.drugs.com/monograph/iron-preparations-oral.html|publisher=The American Society of Health-System Pharmacists|access-date=8 January 2017|url-status=live|archive-url=https://web.archive.org/web/20160522031233/http://www.drugs.com/monograph/iron-preparations-oral.html|archive-date=22 May 2016}}</ref> Other side effects, which may occur with excessive use, include [[iron overload]] and [[iron toxicity]].<ref name=Ric2015/><ref name=WHO2008/> Ferrous salts used as supplements by mouth include [[ferrous fumarate]], [[ferrous gluconate]], [[ferrous succinate]], and [[ferrous sulfate]].<ref name=WHO2008/> Injectable forms include [[iron dextran]] and [[iron sucrose]].<ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free | pages=247–250 }}</ref> They work by providing the iron needed for [[erythropoiesis|making red blood cells]].<ref name=AHFS2017/>

<!-- History and culture -->
Iron pills have been used medically since at least 1681, with an easy-to-use formulation being created in 1832 using chicken [[liver]] extracts and the majority from plants.<ref>{{cite book| vauthors = Upfal J |title=Australian Drug Guide|date=2006|publisher=Black Inc.|isbn=9781863951746|pages=378–379|url=https://books.google.com/books?id=7O9kiqN2q2YC&pg=PA379|language=en|url-status=live|archive-url=https://web.archive.org/web/20170918183856/https://books.google.com/books?id=7O9kiqN2q2YC&pg=PA379|archive-date=18 September 2017}}</ref> Ferrous salt is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Ferrous salts are available as a [[generic medication]] and [[over the counter]].<ref name=Ric2015/> [[Slow release|Slow-release]] formulations, while available, are not recommended.<ref name=BNF69/> In 2021, ferrous sulfate was the 105th most commonly prescribed medication in the United States, with more than 6{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Ferrous Sulfate - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/FerrousSulfate | access-date = 14 January 2024}}</ref>

==Medical uses==
Iron supplements are used to treat or prevent [[iron deficiency]] and [[iron-deficiency anemia]];<ref name="Ferinject SmPC">{{cite web | url = https://www.medicines.org.uk/emc/product/5910 | title = Ferinject 50 mg iron/mL dispersion for injection/infusion | work = emc }}</ref> parenteral irons can also be used to treat functional iron deficiency, where requirements for iron are greater than the body's ability to supply iron such as in inflammatory states. The main criterion is that other causes of anemia have also been investigated, such as [[Pernicious anemia|vitamin B<sub>12</sub>]] or [[folate deficiency]], drug induced or due to other poisons such as lead, as often the anemia has more than one underlying cause.<ref>{{cite web | url = https://www.farbefirma.org/post/the-iron-battle | title = Ferric carboxymaltose | date = 28 June 2023 | quote= It consists of a complex of ferric iron (Fe3+) and carboxymaltose, a carbohydrate molecule. It is a colloidal solution. | publisher = Farbe Firma Pvt Ltd }}</ref>

Iron deficiency anemia is classically a microcytic, hypochromic anemia. Generally, in the UK oral preparations are trialled before using parenteral delivery,<ref name="pmid21561874">{{cite journal | vauthors = Goddard AF, James MW, McIntyre AS, Scott BB | collaboration = British Society of Gastroenterology | title = Guidelines for the management of iron deficiency anaemia | journal = Gut | volume = 60 | issue = 10 | pages = 1309–16 | date = October 2011 | pmid = 21561874 | doi = 10.1136/gut.2010.228874 | s2cid = 52804934 | url = http://www.bsg.org.uk/pdf_word_docs/iron_def.pdf | archive-url = https://web.archive.org/web/20120422205151/http://www.bsg.org.uk/pdf_word_docs/iron_def.pdf | archive-date = 22 April 2012 }}</ref> unless there is a requirement for a rapid response, previous intolerance to oral iron, or likely failure to respond. Intravenous iron may decrease the need for [[blood transfusions]] however it increases the risk of infections when compared to oral iron.<ref>{{cite journal | vauthors = Litton E, Xiao J, Ho KM | title = Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials | journal = BMJ | volume = 347 | pages = f4822 | date = August 2013 | pmid = 23950195 | pmc = 3805480 | doi = 10.1136/bmj.f4822 }}</ref> Daily oral supplementation of iron during pregnancy reduces the risk of maternal anemia, and the effects on infant and other maternal outcomes are not clear.<ref>{{cite journal |vauthors=Finkelstein JL, Cuthbert A, Weeks J, Venkatramanan S, Larvie DY, De-Regil LM, Garcia-Casal MN |date=15 Aug 2024 |title=Daily oral iron supplementation during pregnancy |journal=The Cochrane Database of Systematic Reviews |volume= 2024|issue= 8|pages= CD004736|doi=10.1002/14651858.CD004736.pub6 |pmc=11325660 |pmid=39145520|pmc-embargo-date=August 15, 2025 }}</ref> Another review found tentative evidence that intermittent iron supplements by mouth for mothers and babies are similar to daily supplementation with fewer side effects.<ref name="Cochrane Review on Intermittent Iron Supplementation in Pregnancy">{{cite journal | vauthors = Peña-Rosas JP, De-Regil LM, Gomez Malave H, Flores-Urrutia MC, Dowswell T | title = Intermittent oral iron supplementation during pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 10 | pages = CD009997 | date = October 2015 | pmid = 26482110 | pmc = 7092533 | doi = 10.1002/14651858.CD009997.pub2 }}</ref> Supplements by mouth should be taken on an empty stomach, optionally with a small amount of food to reduce discomfort.<ref>{{Cite encyclopedia|url=https://medlineplus.gov/ency/article/007478.htm|title=Taking iron supplements | encyclopedia = MedlinePlus Medical Encyclopedia| publisher = U.S. National Library of Medicine |language=en|access-date=11 August 2018}}</ref>

===Athletes===
Athletes may be at elevated risk of iron deficiency and so benefit from supplementation, but the circumstances vary between individuals, and dosage should be based on tested [[ferritin]] levels, since in some cases supplementation may be harmful.<ref name=ferr>{{cite journal | vauthors = Clénin G, Cordes M, Huber A, Schumacher YO, Noack P, Scales J, Kriemler S | title = Iron deficiency in sports - definition, influence on performance and therapy | journal = [[Swiss Medical Weekly]] | volume = 145 | pages = w14196 | year = 2015 | pmid = 26512429 | doi = 10.4414/smw.2015.14196 | doi-access = free | type = Review }}</ref>

===Frequent blood donors===
{{main|Blood donation}}
Frequent blood donors may be advised to take iron supplements. [[Canadian Blood Services]] recommends discussing "taking iron supplements with your doctor or pharmacist" as "the amount of iron in most multivitamins may not meet your needs and iron supplements may be necessary".<ref>{{cite web |title=What you need to know about iron |url=https://www.blood.ca/en/blood/am-i-eligible/abcs-eligibility/iron |website=Canadian Blood Services |access-date=30 May 2022}}</ref> The [[American Red Cross]] recommends "taking a multivitamin with 18 mg of iron or an iron supplement with 18–38 mg of elemental iron for 60 days after each blood donation, for 120 days after each power red donation or after frequent platelet donations".<ref>{{cite web |title=Frequent Blood Donors and the Importance of Iron |url=https://www.redcrossblood.org/donate-blood/blood-donation-process/before-during-after/iron-blood-donation/iron-informationforfrequentdonors.html |website=American Red Cross Blood Services |access-date=30 May 2022}}</ref> A 2014 [[Cochrane Review]] found that blood donors were less likely to be deferred for low hemoglobin levels if they were taking oral iron supplements, although 29% of those who took them experienced side effects in contrast to the 17% who took a placebo. It is unknown what the long-term effects of iron supplementation for blood donors may be.<ref>{{cite journal | vauthors = Smith GA, Fisher SA, Doree C, Di Angelantonio E, Roberts DJ | title = Oral or parenteral iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD009532 | date = July 2014 | pmid = 24990381 | doi = 10.1002/14651858.CD009532.pub2 | s2cid = 205200473 | pmc = 11019466 }}</ref>

==Side effects==
Side effects of therapy with oral iron include [[diarrhea]], [[constipation]], or [[epigastric]] abdominal discomfort. Taken after a meal, side effects decrease, but there is an increased risk of interaction with other substances. Side effects are [[dose-dependent]], and the dose may be adjusted.

The patient may notice that their stools become black. This is completely harmless, but patients must be warned about this to avoid unnecessary concern. When iron supplements are given in a liquid form, teeth may reversibly discolor (this can be avoided through the use of a straw). Intramuscular injection can be painful, and brown discoloration may be noticed.

Treatments with [[iron(II) sulfate]] have higher incidence of adverse events than [[Iron polymaltose|iron(III)-hydroxide polymaltose complex]] (IPC)<ref name="pmid17691594">{{cite journal | vauthors = Geisser P | title = Safety and efficacy of iron(III)-hydroxide polymaltose complex / a review of over 25 years experience | journal = Arzneimittel-Forschung | volume = 57 | issue = 6A | pages = 439–452 | year = 2007 | pmid = 17691594 | doi = 10.1055/s-0031-1296693 | s2cid = 70657238 }}</ref><ref name="pmid17691593">{{cite journal | vauthors = Toblli JE, Brignoli R | title = Iron(III)-hydroxide polymaltose complex in iron deficiency anemia / review and meta-analysis | journal = Arzneimittel-Forschung | volume = 57 | issue = 6A | pages = 431–438 | year = 2007 | pmid = 17691593 | doi = 10.1055/s-0031-1296692 | s2cid = 2635923 }}</ref><ref name="pmid17435611">{{cite journal | vauthors = Saha L, Pandhi P, Gopalan S, Malhotra S, Saha PK | title = Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anemia in pregnant women | journal = MedGenMed | volume = 9 | issue = 1 | pages = 1 | date = January 2007 | pmid = 17435611 | pmc = 1924983 }}</ref> or iron bis-glycinate chelate.<ref name="pmid11688081">{{cite journal | vauthors = Szarfarc SC, de Cassana LM, Fujimori E, Guerra-Shinohara EM, de Oliveira IM | title = Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women | journal = Archivos Latinoamericanos de Nutricion | volume = 51 | issue = 1 Suppl 1 | pages = 42–47 | date = March 2001 | pmid = 11688081 }}</ref><ref name="pmid11688084">{{cite journal | vauthors = Ashmead SD | title = The chemistry of ferrous bis-glycinate chelate | journal = Archivos Latinoamericanos de Nutricion | volume = 51 | issue = 1 Suppl 1 | pages = 7–12 | date = March 2001 | pmid = 11688084 }}</ref>

Iron overdose has been one of the leading causes of death caused by toxicological agents in children younger than six years.<ref>{{EMedicine|article|815213|Iron Toxicity}}</ref>

Iron poisoning may result in mortality or short-term and long-term morbidity.<ref>{{cite web | url = http://www.tripdatabase.com/doc/813847-Toxicity-Iron-Overview#content | title = Toxicity, Iron (Overview) | archive-url = https://web.archive.org/web/20160308211454/https://www.tripdatabase.com/doc/813847-Toxicity-Iron-Overview | archive-date = 8 March 2016 | work = Tripdatabase.com| access-date = 21 December 2012 }}</ref>

=== Infection risk ===
Because one of the functions of elevated [[ferritin]] (an acute phase reaction protein) in acute infections is thought to be to sequester iron from bacteria, it is generally thought that iron supplementation (which circumvents this mechanism) should be avoided in patients who have active bacterial infections. Replacement of iron stores is seldom such an emergency that it cannot wait for any such acute infection to be treated.

Some studies have found that iron supplementation can lead to an increase in [[infectious disease]] morbidity in areas where bacterial infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in [[diarrhea]] overall and enteropathogen shedding. Iron deficiency protects against infection by creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as ''[[Salmonella typhimurium]]'' or ''[[Entamoeba histolytica]]''. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases; however this is a different question than the question of supplementation in individuals who are already ill with a bacterial infection.<ref>{{cite journal | vauthors = Oppenheimer SJ | title = Iron and its relation to immunity and infectious disease | journal = The Journal of Nutrition | volume = 131 | issue = 2S–2 | pages = 616S–635S | date = February 2001 | pmid = 11160594 | doi = 10.1093/jn/131.2.616S | doi-access = free }}</ref>

Children living in areas prone to malaria infections are also at risk of developing anemia. It was thought that iron supplementation given to such children could increase the risk of malaria infection in them. A Cochrane systematic review published in 2016 found high-quality evidence that iron supplementation does not increase the risk of clinical malaria in children.<ref>{{cite journal | vauthors = Neuberger A, Okebe J, Yahav D, Paul M | title = Oral iron supplements for children in malaria-endemic areas | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | issue = 2 | pages = CD006589 | date = February 2016 | pmid = 26921618 | pmc = 4916933 | doi = 10.1002/14651858.CD006589.pub4 }}</ref>

==Contraindications==
Contraindications often depend on the substance in question. Documented [[hypersensitivity]] to any ingredients and anemias without proper work-up (i.e., documentation of iron deficiency) is true of all preparations. Some can be used in iron deficiency, others require iron deficiency anaemia to be present. Some are also contraindicated in [[rheumatoid arthritis]].<ref name="Cosmofer SmPC">{{cite web | url = https://www.medicines.org.uk/emc/medicine/14139 | title = Cosmofer – Summary of Product Characteristics (SPC) | work = eMC | archive-url = https://web.archive.org/web/20140426215550/http://www.medicines.org.uk/emc/medicine/14139 | archive-date = 26 April 2014 | access-date = 21 December 2012 }}</ref>

===Hemochromatosis===
Individuals may be genetically predisposed to excessive iron absorption, as is the case with those with [[HFE hereditary haemochromatosis|HFE hereditary hemochromatosis]]. Within the general population, 1 out of 400 people has the homozygous form of this genetic trait, and 1 out of every 10 people has its heterozygous form.<ref name="Nielson">{{cite journal | vauthors = Nielsen P, Nachtigall D | title = Iron supplementation in athletes. Current recommendations | journal = Sports Medicine | volume = 26 | issue = 4 | pages = 207–216 | date = October 1998 | pmid = 9820921 | doi = 10.2165/00007256-199826040-00001 | s2cid = 25517866 }}</ref> Neither individuals with the homozygous nor heterozygous form should take iron supplements.<ref name="Nielson"/>

== Interactions ==

Non-[[heme]] iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and the other drug. Examples include [[tetracycline]], [[penicillamine]], [[methyldopa]], [[levodopa]], [[bisphosphonates]], and [[Quinolone antibiotic|quinolones]]. The same can occur with elements in food, such as [[calcium]], which impacts both heme and non-heme iron absorption.<ref>{{cite journal | vauthors = Zijp IM, Korver O, Tijburg LB | title = Effect of tea and other dietary factors on iron absorption | journal = Critical Reviews in Food Science and Nutrition | volume = 40 | issue = 5 | pages = 371–398 | date = September 2000 | pmid = 11029010 | doi = 10.1080/10408690091189194 | s2cid = 12423113 }}</ref> Absorption of iron is better at a low pH (i.e. an acidic environment), and absorption is decreased if there is a simultaneous intake of antacids.

Many other substances decrease the rate of non-heme iron absorption. One example is [[tannins]] from foods such as [[tea]]<ref>{{cite journal | vauthors = Delimont NM, Haub MD, Lindshield BL | title = The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative Review | journal = Current Developments in Nutrition | volume = 1 | issue = 2 | pages = 1–12 | date = February 2017 | pmid = 29955693 | pmc = 5998341 | doi = 10.3945/cdn.116.000042 }}</ref> and [[phytic acid]].<ref name="Reddy 1996">{{cite journal | vauthors = Reddy MB, Hurrell RF, Juillerat MA, Cook JD | title = The influence of different protein sources on phytate inhibition of nonheme-iron absorption in humans | journal = The American Journal of Clinical Nutrition | volume = 63 | issue = 2 | pages = 203–207 | date = February 1996 | pmid = 8561061 | doi = 10.1093/ajcn/63.2.203 | doi-access = free }}</ref> Because iron from plant sources is less easily absorbed than the heme-bound iron of animal sources, [[vegetarian]]s and [[vegan]]s should have a somewhat higher total daily iron intake than those who eat meat, fish or poultry.<ref>{{cite web | vauthors = [[Reed Mangels|Mangels R]] | url = http://www.vrg.org/nutrition/iron.htm | title = Iron in the vegan diet | work = The Vegetarian Resource Group }}</ref><ref name="Henjum 2021">{{cite journal | vauthors = Henjum S, Groufh-Jacobsen S, Stea TH, Tonheim LE, Almendingen K | title = Iron Status of Vegans, Vegetarians and Pescatarians in Norway | journal = Biomolecules | volume = 11 | issue = 3 | page = 454 | date = March 2021 | pmid = 33803700 | pmc = 8003004 | doi = 10.3390/biom11030454 | doi-access = free }}</ref>

Taken after a meal, there are fewer side effects, but there is also less absorption because of interaction and pH alteration. Generally, an interval of 2–3 hours between the iron intake and that of other drugs seems advisable, but is less convenient for patients and can impact compliance.

==History==
The first pills were commonly known as Blaud's pills,<ref>{{cite web | url = http://www.merriam-webster.com/medical/blaud's%20pill | title = Blaud's pill – Medical Definition | work = Merriam-Webster | archive-url = https://web.archive.org/web/20100219015237/http://www.merriam-webster.com/medical/blaud%27s%20pill | archive-date = 19 February 2010 | access-date = 21 December 2012 }}</ref> which were named after [[P. Blaud of Beaucaire]], the French physician who introduced and started the use of these medications as a treatment for patients with [[anemia]].<ref name=TMHP>{{cite-TMHP|''P. Blaud of Beaucaire'', ''Blaud's Pills for Anemia'', ''Iron pills'', ''Iron''}}, p. 435.</ref>

==Administration==

===By mouth===
{{redirect|Proferrin|the pupil dilator|Prefrin}}
Iron can be supplemented [[oral route|by mouth]] using various forms, such as [[iron(II) sulfate]]. This is the most common and well-studied soluble iron [[salt]] sold under brand names such as Feratab, Fer-Iron, and Slow-FE. It is in complex with [[gluconate]], [[dextran]], [[carbonyl iron]], and other salts. [[Ascorbic acid]], vitamin C, increases the absorption of non-heme sources of iron, but not to a clinically significant degree.<ref>{{cite journal | vauthors = Deng J, Ramelli L, Li PY, Eshaghpour A, Schuenemann GE, Crowther MA | title=Efficacy of Vitamin C with Iron Supplementation in Iron Deficiency Anemia Patients: A Systematic Review and Meta-Analysis | journal=Blood | publisher=American Society of Hematology | volume=142 | issue=Supplement 1 | date=2023-11-02 | issn=0006-4971 | doi=10.1182/blood-2023-174801 | doi-access=free | pages=1091–1091}}</ref>

Heme iron polypeptide (HIP) (e.g., Proferrin ES and Proferrin Forte) can be used when regular iron supplements such as ferrous sulfate or ferrous fumarate are not tolerated or absorbed. A clinical study demonstrated that HIP increased serum iron levels 23 times greater than ferrous fumarate on a milligram-per-milligram basis.<ref>{{cite journal | vauthors = Seligman PA, Moore GM, Schleicher RB |title=Clinical studies of hip: An oral heme-iron product |journal=Nutrition Research |volume=20 |issue=9 |year=2000 |pages=1279–86 |doi=10.1016/s0271-5317(00)00215-3 |s2cid=84515114 }}</ref>

Another alternative is ferrous [[glycine]] [[sulfate]] or ferroglycine sulfate, which has fewer gastrointestinal side effects than standard preparations such as iron fumarate.<ref>{{cite journal | vauthors = Aronstam A, Aston DL | title = A comparative trial of a controlled-release iron tablet preparation ('Ferrocontin' Continus) and ferrous fumarate tablets | journal = Pharmatherapeutica | volume = 3 | issue = 4 | pages = 263–267 | year = 1982 | pmid = 7146040 }}</ref> {{Better source needed|date=January 2020}} It is unusual among oral preparations of iron supplements in that the iron in this preparation has very high oral bioavailability, especially in the liquid formulation. This option should be evaluated before resorting to parenteral therapy. It is especially useful in iron deficiency anemia associated with [[autoimmune gastritis]] and ''[[Helicobacter pylori]]'' gastritis, where it generally has a satisfactory effect.<ref>{{cite journal | vauthors = Hershko C, Ianculovich M, Souroujon M | title = Decreased treatment failure rates following duodenal release ferrous glycine sulfate in iron deficiency anemia associated with autoimmune gastritis and Helicobacter pylori gastritis | journal = Acta Haematologica | volume = 118 | issue = 1 | pages = 19–26 | year = 2007 | pmid = 17426393 | doi = 10.1159/000101701 | s2cid = 46720321 }}</ref>

Since iron stores in the body are generally depleted, and there is a limit to what the body can process (about 2–6&nbsp;mg/kg of body mass per day; i.e. for a 100&nbsp;kg/220&nbsp;lb man this is equal to a maximum dose of 200–600&nbsp;mg/per day) without [[iron poisoning]], this is a chronic therapy which may take 3–6 months.<ref>{{cite web | url = http://www.webmd.com/a-to-z-guides/iron-poisoning | title = Iron Poisoning | archive-url = https://web.archive.org/web/20120412155245/http://www.webmd.com/a-to-z-guides/iron-poisoning | archive-date = 12 April 2012 | work = Webmd.com | date = 27 September 2012 | access-date = 21 December 2012 }}</ref>

Due to the frequent intolerance of oral iron and the slow improvement, parenteral iron is recommended in many indications.<ref>{{cite book |author=National Clinical Guideline Centre |title=Anaemia Management in Chronic Kidney Disease |location=London |publisher=Royal College of Physicians |year=2015 |series=NICE Guideline, No. 8 |url=https://www.ncbi.nlm.nih.gov/books/NBK299242/ |pmid=26065064 |url-status=live |archive-url=https://web.archive.org/web/20170918183856/https://www.ncbi.nlm.nih.gov/books/NBK299242/ |archive-date=18 September 2017 }}</ref><ref>{{cite journal | vauthors = Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, Mitton S, Orchard T, Rutter M, Younge L, Lees C, Ho GT, Satsangi J, Bloom S | title = Guidelines for the management of inflammatory bowel disease in adults | journal = Gut | volume = 60 | issue = 5 | pages = 571–607 | date = May 2011 | pmid = 21464096 | doi = 10.1136/gut.2010.224154 | url = http://chinesefms.com/doc/zhw/doc_zhw_xzzn/201104/P020110416418498436822.pdf | url-status = dead | access-date = 8 August 2012 | collaboration = IBD Section of the British Society of Gastroenterology | s2cid = 8269837 | archive-url = https://web.archive.org/web/20130621085124/http://chinesefms.com/doc/zhw/doc_zhw_xzzn/201104/P020110416418498436822.pdf | archive-date = 21 June 2013 }}</ref>

====Food fortification====

Fortified foods with iron such as [[breakfast cereal]]s and [[wheat flour]] are effective in increasing hemoglobin levels and lowering prevalence of anemia and iron deficiency.<ref>{{cite journal |vauthors=Gera T, Sachdev HS, Boy E  |date=2012 |title=Effect of iron-fortified foods on hematologic and biological outcomes: systematic review of randomized controlled trials |url=https://www.sciencedirect.com/science/article/pii/S0002916523028915 |journal=Am J Clin Nutr |volume=96 |issue=2 |pages=309-324 |doi=10.3945/ajcn.111.031500 |pmc= |pmid=22760566}}</ref><ref>{{cite journal |vauthors=Helmyati S, Lusmilasari L, Sandhi A, Hardiyanti M, Rosilia G, Rachmawati YN, Aristyarini M |date=2025 |title=Systematic review on supplementation, fortification, and food-based interventions for preventing iron deficiency anemia in low- and middle-income countries |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC11742596/ |journal=Asia Pac J Clin Nutr |volume=34 |issue=1 |pages=10-35 |doi=10.6133/apjcn.202502_34(1).0002 |pmc=11742596 |pmid=39828255}}</ref><ref>{{cite journal |vauthors=Dorbu AD, Waddel HB, Chadha MK, de Romaña DL, Arabi M, Moore RH, Mehta C, Pachón H |date=2025 |title=Nutritional Anemia Reductions Due to Food Fortification Among Women of Childbearing Age: A Literature Review and Bayesian Meta-Analysis |url=https://onlinelibrary.wiley.com/doi/full/10.1111/mcn.13801 |journal=Matern Child Nutr|volume= |issue= |pages=e13801 |doi=10.1111/mcn.13801 |pmc= |pmid=39899434|doi-access=free }}</ref> A 2021 Cochrane Review found that wheat flour fortified with iron may reduce anemia by 27%.<ref>{{cite journal |vauthors=Field MS, Mithra P, Peña-Rosas JP |date=2021 |title=Wheat flour fortification with iron and other micronutrients for reducing anaemia and improving iron status in populations |url=https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011302.pub3/full |journal=Cochrane Database Syst Rev |volume=1 |issue=1 |pages=CD011302 |doi=10.1002/14651858.CD011302.pub3 |pmc=8407500 |pmid=33461239}}</ref> Fortified rice may increase haemoglobin concentrations and reduce iron deficiency in the general population but has not been found to reduce anemia.<ref>{{cite journal |vauthors=Peña-Rosas JP, Mithra P, Unnikrishnan B, Kumar N, De-Regil LM, Nair NS, Garcia-Casal MN, Solon JA |date=2019 |title=Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition |url=https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009902.pub2/full/hu |journal=Cochrane Database Syst Rev |volume=2019 |issue=10 |pages=CD009902 |doi=10.1002/14651858.CD009902.pub2 |pmc=6814158 |pmid=31684687}}</ref> In 2023, the [[World Health Organization]] recommended fortification of rice with iron as a public health strategy to improve the iron status of populations in regions where rice is a staple food.<ref>{{Cite web|date=2023|title=Fortification of Rice|url=https://www.who.int/tools/elena/interventions/rice-fortification|website=World Health Organization|language=en-GB|archive-date=April 15, 2025|archive-url=https://web.archive.org/web/20250415095209/https://www.who.int/tools/elena/interventions/rice-fortification|url-status=live}}</ref>

===By injection===
Iron therapy (intravenously or intramuscular) is given when therapy by mouth has failed (not tolerated), oral absorption is seriously compromised (by illnesses, or when the person cannot swallow), benefit from oral therapy cannot be expected, or fast improvement is required (for example, prior to elective surgery).<ref name="pmid9070014">{{cite journal | vauthors = Kumpf VJ | title = Parenteral iron supplementation | journal = Nutrition in Clinical Practice | volume = 11 | issue = 4 | pages = 139–146 | date = August 1996 | pmid = 9070014 | doi = 10.1177/0115426596011004139 }}</ref> [[Parenteral|Parenteral therapy]] is more expensive than oral iron preparations and is not suitable during the first trimester of [[pregnancy]].<ref name="Ferinject SmPC" />

There are cases where parenteral iron is preferable over oral iron. These are cases where oral iron is not tolerated, where the [[haemoglobin]] needs to be increased quickly (e.g. postpartum, postoperatively, post-transfusion), where there is an underlying inflammatory condition (e.g. inflammatory bowel disease) or renal patients, the benefits of parenteral iron far outweigh the risks.

Low-certainty evidence suggests that IBD-related anemia treatment with [[Intravenous iron infusion|intravenous (IV) iron infusion]] may be more effective than [[Oral iron|oral iron therapy]], with fewer people needing to stop treatment early due to adverse effects.<ref name=":0">{{cite journal | vauthors = Gordon M, Sinopoulou V, Iheozor-Ejiofor Z, Iqbal T, Allen P, Hoque S, Engineer J, Akobeng AK | title = Interventions for treating iron deficiency anaemia in inflammatory bowel disease | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD013529 | date = January 2021 | pmid = 33471939 | pmc = 8092475 | doi = 10.1002/14651858.CD013529.pub2 }}</ref> The type of iron preparation may be an important determinant of clinical benefit. Moderate-certainty evidence suggests response to treatment may be higher when IV [[ferric carboxymaltose]], rather than IV [[iron sucrose]] preparation is used, despite very-low certainty evidence of increased adverse effects, including bleeding, in those receiving ferric carboxymaltose treatment.<ref name=":0" />

In many cases, use of intravenous iron such as ferric carboxymaltose has lower risks of adverse events than a blood transfusion and, as long as the person is stable, is a better alternative.<ref>{{cite journal | vauthors = Moore RA, Gaskell H, Rose P, Allan J | title = Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data | journal = BMC Blood Disorders | volume = 11 | pages = 4 | date = September 2011 | pmid = 21942989 | pmc = 3206450 | doi = 10.1186/1471-2326-11-4 | doi-access = free }}</ref> Ultimately this always remains a clinical decision based on local guidelines, although national guidelines are increasingly stipulating IV iron in certain groups of patients.<ref>{{cite journal | vauthors = Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P | title = 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC | journal = European Heart Journal | volume = 37 | issue = 27 | pages = 2129–2200 | date = July 2016 | pmid = 27206819 | doi = 10.1093/eurheartj/ehw128 | author22 = ESC Scientific Document Group | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dignass AU, Gasche C, Bettenworth D, Birgegård G, Danese S, Gisbert JP, Gomollon F, Iqbal T, Katsanos K, Koutroubakis I, Magro F, Savoye G, Stein J, Vavricka S | title = European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases | journal = Journal of Crohn's & Colitis | volume = 9 | issue = 3 | pages = 211–222 | date = March 2015 | pmid = 25518052 | doi = 10.1093/ecco-jcc/jju009 | doi-access = free }}</ref>

A Cochrane Review of controlled trials comparing [[Intravenous iron infusion|intravenous (IV) iron therapy]] with oral iron supplements in people with [[chronic kidney disease]], found low-certainty evidence that people receiving IV-iron treatment were 1.71 times as likely to reach their target [[hemoglobin]] levels.<ref name=":1">{{cite journal | vauthors = O'Lone EL, Hodson EM, Nistor I, Bolignano D, Webster AC, Craig JC | title = Parenteral versus oral iron therapy for adults and children with chronic kidney disease | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 2 | pages = CD007857 | date = February 2019 | pmid = 30790278 | pmc = 6384096 | doi = 10.1002/14651858.CD007857.pub3 | collaboration = Cochrane Kidney and Transplant Group }}</ref> Overall, hemoglobin was 0.71g/dl higher than those treated with oral iron supplements. Iron stores in the liver, estimated by serum [[ferritin]], were also 224.84&nbsp;μg/L higher in those receiving IV-iron.<ref name=":1" /> However, there was also low-certainty evidence that allergic reactions were more likely following IV-iron therapy. It was unclear whether the type of iron therapy administration affects the risk of death from any cause, including cardiovascular, or whether it may alter the number of people who may require a blood transfusion or dialysis.<ref name=":1" />

Soluble iron salts have a significant risk of adverse effects and can cause toxicity due to damage to cellular macromolecules. Delivering iron parenterally has utilised various molecules to limit this. This has included [[dextrans]], [[sucrose]], carboxymaltose, and Isomaltoside 1000.{{citation needed|date=July 2015}}

One formulation of parenteral iron is iron dextran which covers the old high molecular weight (brand name Dexferrum) and the much safer low molecular iron dextrans (brand names including Cosmofer and Infed).<ref>{{cite journal | vauthors = Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J | title = On the relative safety of parenteral iron formulations | journal = Nephrology, Dialysis, Transplantation | volume = 19 | issue = 6 | pages = 1571–1575 | date = June 2004 | pmid = 15150356 | doi = 10.1093/ndt/gfh185 | doi-access =  }}</ref>

Iron [[sucrose]] has an occurrence of allergic reactions of less than 1 in 1000.<ref name=fass-venofer>{{cite web | url = http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=20000211000213&DocTypeID=7 | title = Venofer | archive-url = https://web.archive.org/web/20111001011331/http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=20000211000213&DocTypeID=7 | archive-date = 1 October 2011 | work = [[FASS (drug formulary)]] | language = Swedish | quote = Allergiska reaktioner (inträffar hos färre än 1 av 1 000 patienter)" and "Vanliga (inträffar hos färre än 1 av 10 patienter): Tillfälliga smakförändringar (speciellt metallsmak). }}</ref> A common side effect is taste changes, especially a [[metallic taste]], occurring in between 1 in 10 and 1 in 100 treated patients.<ref name=fass-venofer/> It has a maximum dose of 200&nbsp;mg on each occasion according to the SPC, but it has been given in doses of 500&nbsp;mg. Doses can be given up to three times a week.<ref>{{cite web |url=https://www.medicines.org.uk/emc/medicine/24168 |title=Venofer (iron sucrose) - Summary of Product Characteristics (SmPC) | work = eMC |access-date=7 March 2017 |url-status=live |archive-url=https://web.archive.org/web/20170308044906/https://www.medicines.org.uk/emc/medicine/24168 |archive-date=8 March 2017 }}</ref>

Iron carboxymaltose is marketed as Ferinject,<ref name="Ferinject SmPC" /> Injectafer,<ref name="Injectafer FDA label" /><ref>{{cite web | title=Drug Approval Package: Injectafer (ferric carboxymaltose) Injection NDA #203565 | website=U.S. [[Food and Drug Administration]] (FDA) | date=4 September 2013 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203565Orig1s000TOC.cfm | access-date=8 February 2024}}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}}</ref> and Iroprem in various countries.<ref name="CançadoMuñoz2011"/> The most common side effects are [[headaches]] which occur in 3.3%, and hypophosphatemia, which occurs in more than 35%.<ref name="Ferinject SmPC" /><ref name="Injectafer FDA label">{{cite web | title=Injectafer- ferric carboxymaltose injection injection, solution; Injectafer- ferric carboxymaltose injection, solution | website=DailyMed | date=1 May 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=517b4a19-45b3-4286-9f6a-ced4e10447de | access-date=8 February 2024}}</ref>

Iron isomaltoside 1000 (brand name Monofer) is a formulation of parenteral iron that has a matrix structure that results in very low levels of free iron and labile iron. It can be given at high doses – 20&nbsp;mg/kg in a single visit – with no upper dose limit. This formulation has the benefit of giving a full iron correction in a single visit.<ref>{{cite journal | vauthors = Jahn MR, Andreasen HB, Fütterer S, Nawroth T, Schünemann V, Kolb U, Hofmeister W, Muñoz M, Bock K, Meldal M, Langguth P | title = A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications | journal = European Journal of Pharmaceutics and Biopharmaceutics | volume = 78 | issue = 3 | pages = 480–491 | date = August 2011 | pmid = 21439379 | doi = 10.1016/j.ejpb.2011.03.016 }}</ref><ref name="CançadoMuñoz2011">{{cite journal | vauthors = Cançado RD, Muñoz M | title = Intravenous iron therapy: how far have we come? | journal = Revista Brasileira de Hematologia e Hemoterapia | volume = 33 | issue = 6 | pages = 461–469 | year = 2011 | pmid = 23049364 | pmc = 3459360 | doi = 10.5581/1516-8484.20110123 | doi-broken-date = 1 November 2024 }}</ref>

[[Ferric maltol]], marketed as Accrufer<ref name="Drug Approval Package: Accrufer">{{cite web | title=Drug Approval Package: Accrufer | website=U.S. [[Food and Drug Administration]] (FDA) | date=14 August 2019 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/212320Orig1s000TOC.cfm | access-date=8 February 2024}}</ref> and Ferracru, is available in oral and intravenous preparations. When used as a treatment for IBD-related anemia, very low certainty evidence suggests a marked benefit with oral ferric maltol compared with placebo. However, it was unclear whether the IV preparation was more effective than oral ferric maltol.<ref name=":0" />

== References ==
{{reflist}}

{{Antianemic preparations}}
{{Dietary supplement}}
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{{DEFAULTSORT:Iron Supplements}}
[[Category:Dietary supplements]]
[[Category:Drugs acting on the blood and blood forming organs]]
[[Category:World Health Organization essential medicines]]
[[Category:Wikipedia medicine articles ready to translate]]