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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|last1 vauthors = Hamilton|first1=Richart 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 formularyNational 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/>
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<!-- History and culture -->
Iron pills have been used medically since at least 1681, with an easy-to-use formulation being created in 1832.<ref>{{cite book|last1 vauthors = Upfal|first1=Jonathan 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=2017-09-18}}</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]] formulations, while available, are not recommended.<ref name=BNF69/> In 2020, ferrous sulfate was the 116th most commonly prescribed medication in the United States, with more than 5{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 2020 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date = 7 October 2022}}</ref><ref>{{cite web | title = Ferrous Sulfate - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/FerrousSulfate | access-date = 7 October 2022}}</ref>
==Medical uses==
Iron supplements are used to treat [[Iron deficiency (medicine)|iron deficiency]] and [[iron-deficiency anemia]];<ref name="medicines.org.uk">[{{cite web | url = http://www.medicines.org.uk/EMC/medicine/24167/SPC/Ferinject+(ferric+carboxymaltose)/ | title = Ferinject (ferric n 2012-12-21.] {{webarchive| work = eMC | archive-url = https://web.archive.org/web/20140309172326/http://www.medicines.org.uk/EMC/medicine/24167/SPC/Ferinject+(ferric+carboxymaltose)/ | archive-date = 9 March 2014-03-09 }}</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. [https://www.farbefirma.org/post/the-iron-battle Ferric carboxymaltose: It consists of a complex of ferric iron (Fe3+) and carboxymaltose, a carbohydrate molecule. It is a colloidal solution.]<ref>{{Cite web |last=Farbe |first=Firma |title=Iron |url=https://www.farbefirma.org/post/the-iron-battle | 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 and, Scott BB (May| 2005)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 | url = [http://www.bsg.org.uk/pdf_word_docs/iron_def.pdf Guidelines for the management of iron deficiency anaemia] {{webarchive| archive-url = https://web.archive.org/web/20120422205151/http://www.bsg.org.uk/pdf_word_docs/iron_def.pdf | archive-date =2012-04- 22 April 2012 }}. British Society of Gastroenterology</ref> unless there is the 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 |last vauthors = Litton|first= E|author2=Xiao, Xiao J, |author3=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 (Clinical| Researchvolume Ed.)|date=Aug 15,347 2013|volume=347| pages = f4822 | date = August 2013 | pmid = 23950195 | pmc = 3805480 | doi = 10.1136/bmj.f4822|pmc=3805480 }}</ref> A 2015 [[Cochrane Collaboration]] review found that daily oral supplementation of iron during pregnancy reduces the risk of maternal anemia and that effects on infant and on other maternal outcomes are not clear.<ref>{{Citecite journal | vauthors = Peña-Rosas JP, De-Regil LM, Garcia-Casal MN, Dowswell T | title = Daily oral iron supplementation during pregnancy. | journal = The Cochrane Database Systof RevSystematic Reviews | volume = 2015 | issue = 7 | pages =CD0047361 CD004736 | yeardate = July 2015 | pmid = 26198451 | pmc = 4233117 | doi = 10.1002/14651858.CD004736.pub5|pmid=26198451 | pmc = 4233117 }}</ref> Another review found tentative evidence that intermittent iron supplements by mouth for mothers and babies is similar to daily supplementation with fewer side effects.<ref name="Cochrane Review on Intermittent Iron Supplementation in Pregnancy">{{cite journal |last1 vauthors = Peña-Rosas|first1=Juan PabloJP, 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 =19 October 2015 | pmid = 26482110 | pmc = 7092533 | doi = 10.1002/14651858.CD009997.pub2|pmid=26482110|volume=2015|issue=10|pages=CD009997|pmc=7092533 }}</ref> Supplements by mouth should be taken on an empty stomach, optionally with a small amount of food to reduce discomfort.<ref>{{Cite web|url=https://medlineplus.gov/ency/article/007478.htm|title=Taking iron supplements: MedlinePlus Medical Encyclopedia|website=medlineplus.gov|language=en|access-date=2018-08-11}}</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 MedMedical WklyWeekly | volume = 145 | pages = w14196 | year = 2015 | pmid = 26512429 | doi = 10.4414/smw.2015.14196 |type=Review| 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% that took a placebo. It is unknown what the long-term effects of iron supplementation for blood donors may be.<ref>{{cite journal |last1 vauthors = Smith |first1=GrahamGA, |last2=Fisher |first2=SheilaSA, |last3=Doree |first3=CarolynC, |last4=Di Angelantonio |first4=EmanueleE, |last5=Roberts DJ |first5=David |title = Oral or parenteral iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors | journal = The Cochrane Database of Systematic Reviews|date=2014 | issue = 7 | pages = CD009532 |doi date =10.1002/14651858.CD009532.pub2 July 2014 | pmid = 24990381 |s2cid doi =205200473 |url=https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009532.pub2/full |access-date s2cid =31 May205200473 2022}}</ref>
==Side effects==
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 |author vauthors = Geisser P | title = Safety and efficacy of iron(III)-hydroxide polymaltose complex / a review of over 25 years experience | journal =Arzneimittelforschung Arzneimittel-Forschung | volume = 57 | issue = 6A | pages =439–52 439–452 | 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 =Arzneimittelforschung Arzneimittel-Forschung | volume = 57 | issue = 6A | pages =431–8 431–438 | 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 sulfatesulphate in the treatment of iron deficiency anemia in pregnant women | journal = MedGenMed | volume = 9 | issue = 1 |page pages = 1 |year 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 =Arch LatinoamArchivos NutrLatinoamericanos De Nutricion | volume = 51 | issue = 1 Suppl 1 | pages =42–7 42–47 |year date = March 2001 | pmid = 11688081 }}</ref><ref name="pmid11688084">{{cite journal |author vauthors = Ashmead SD | title = The chemistry of ferrous bis-glycinate chelate | journal =Arch LatinoamArchivos NutrLatinoamericanos De Nutricion | volume = 51 | issue = 1 Suppl 1 | pages = 7–12 |year 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 6 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)] {{webarchive| archive-url = https://web.archive.org/web/20160308211454/https://www.tripdatabase.com/doc/813847-Toxicity-Iron-Overview | archive-date = 8 March 2016-03-08 }}.| work = Tripdatabase.com.| Retrievedaccess-date on= 2012-12-21. 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 situation 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 Relationrelation to Immunityimmunity and Infectiousinfectious Diseasedisease | 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 |pmid=11160594 |year=2001 |last1=Oppenheimer |first1=Stephen J. |doi-access = free }}</ref>
Children living in areas prone for malarial infections are also at risk of developing anemia. It was thought that iron supplementation given to such children could increase the risk of malarial 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 |last1 vauthors = Neuberger|first1= A|last2=, Okebe|first2= J|last3=, Yahav|first3= D|last4=, Paul|first4= M | title = Oral iron supplements for children in malaria-endemic areas. | journal = The Cochrane Database of Systematic Reviews |date volume =27 February2 2016|volume=2016| issue = 2 | pages = CD006589 | date = February 2016 | pmid = 26921618 | pmc = 4916933 | doi = 10.1002/14651858.CD006589.pub4|pmid=26921618|pmc=4916933 }}</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>[http://www.medicines.org.uk/emc/medicine/14139 CosmoFer – Summary of Product Characteristics (SPC) –| work = (eMC)] {{webarchive| archive-url = https://web.archive.org/web/20140426215550/http://www.medicines.org.uk/emc/medicine/14139 | archive-date =2014-04- 26 April 2014 }}. Medicines.org.uk. Retrieved on 2012-12-21.</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">{{Citecite journal |last1 vauthors = Nielsen |first1=PeterP, |last2=Nachtigall |first2=DetlefD |date=October 1998title |title= Iron supplementation in athletes. Current recommendations |url=https://pubmed.ncbi.nlm.nih.gov/9820921 |journal = Sports Medicine (Auckland, N.Z.) | volume = 26 | issue = 4 | pages = 207–216 | date = October 1998 | pmid = 9820921 | doi = 10.2165/00007256-199826040-00001 |issn=0112-1642 |pmid=9820921s2cid |access-date=November 29,25517866 2022 |s2cid=25517866|url-access=subscription}}</ref> Neither individuals with the homozygous or 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 [[quinolones]]. The same can occur with elements in food, such as [[calcium]], which impacts both heme and non-heme iron absorption.<ref>{{cite journal |last1=Zjip |first1=Itske |last2=Korver |first2=Onno |last3=Tijburg |first3=Lillian |title=Effect of Tea and Other Dietary Factors on Iron Absorption |journal=Critical Reviews in Food Science and Nutrition |date=2000 |volume=40 |issue=5 |pages=371–398 |doi=10.1080/10408690091189194 |pmid=11029010 |s2cid=12423113 |url=https://www.tandfonline.com/doi/abs/10.1080/10408690091189194 |access-date=31 May 2022}}</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. ▼
▲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 [[quinolones]]. The same can occur with elements in food, such as [[calcium]], which impacts both heme and non-heme iron absorption.<ref>{{cite journal | last1=Zjip |first1vauthors = Itske |last2=Zijp IM, Korver |first2=OnnoO, |last3=Tijburg |first3=LillianLB | title = Effect of Teatea and Otherother Dietarydietary Factorsfactors on Ironiron Absorptionabsorption | journal = Critical Reviews in Food Science and Nutrition | date=2000 |volume = 40 | issue = 5 | pages = 371–398 | doi date = 10.1080/10408690091189194 September 2000 | pmid = 11029010 | s2cid=12423113 |url=https://www.tandfonline.com/doi /abs/ = 10.1080/10408690091189194 | access-date s2cid = 31 May12423113 2022}}</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 |last1=Delimont |first1=Nicole |last2=Haub |first2=Mark |last3=Lindshield |first3=Brian |title=The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative Review |journal=Current Developments in Nutrition |date=2017 |volume=1 |issue=2 |pages=e000042 |doi=10.3945/cdn.116.000042 |pmid=29955693 |pmc=5998341 }}</ref> and [[phytic acid]].<ref name="Reddy 1996">{{cite journal |last1=Reddy |first1=MB |last2=Hurrell |first2=RF |last3=Juillerat |first3=MA |last4=Cook |first4=JD |title=The influence of different protein sources on phytate inhibition of nonheme-iron absorption in humans |journal=American Journal of Clinical Nutrition |date=1996 |volume=63 |issue=2 |pages=203–207 |doi=10.1093/ajcn/63.2.203|pmid=8561061 |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>[[Reed Mangels|Mangels, Reed]]. [http://www.vrg.org/nutrition/iron.htm Iron in the vegan diet]. The Vegetarian Resource Group.</ref><ref name="Henjum 2021">{{cite journal |last1=Henjum |first1=Sigrun |last2=Groufh-Jacobsen |first2=Synne |last3=Stea |first3=Tonja Holte |last4=Tonheim |first4=Live Edvardsen |last5=Almendingen |first5=Kari |last6=Nurchi |first6=Valeria |title=Iron Status of Vegans, Vegetarians and Pescatarians in Norway |journal=Biomolecules |date=2021 |volume=11 |issue=3 |page=454 |doi=10.3390/biom11030454|pmid=33803700 |pmc=8003004 |doi-access=free }}</ref> ▼
▲Many other substances decrease the rate of non-heme iron absorption. One example is [[tannins]] from foods such as [[tea]]<ref>{{cite journal | last1 vauthors = Delimont |first1=NicoleNM, |last2=Haub |first2=MarkMD, |last3=Lindshield BL | first3=Brian |title = The Impact of Tannin Consumption on Iron Bioavailability and Status: A Narrative Review | journal = Current Developments in Nutrition | date=2017 |volume = 1 | issue = 2 | pages = e000042 1–12 | doi date = 10.3945/cdn.116.000042 February 2017 | pmid = 29955693 | pmc = 5998341 | doi = 10.3945/cdn.116.000042 }}</ref> and [[phytic acid]].<ref name="Reddy 1996">{{cite journal | last1 vauthors = Reddy |first1=MB , |last2=Hurrell |first2=RF , |last3=Juillerat |first3=MA , |last4=Cook |first4=JD | title = The influence of different protein sources on phytate inhibition of nonheme-iron absorption in humans | journal = The American Journal of Clinical Nutrition | date=1996 |volume = 63 | issue = 2 | pages = 203–207 | date = February 1996 | pmid = 8561061 | doi = 10.1093/ajcn/63.2.203 |pmid=8561061 | 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>[[Reed Mangels|Mangels, Reed]]. [http://www.vrg.org/nutrition/iron.htm Iron in the vegan diet]. The Vegetarian Resource Group.</ref><ref name="Henjum 2021">{{cite journal | last1 vauthors = Henjum |first1=SigrunS, |last2=Groufh-Jacobsen |first2=SynneS, |last3=Stea |first3=TonjaTH, Holte |last4=Tonheim |first4=LiveLE, Edvardsen |last5=Almendingen |first5=KariK | last6=Nurchi |first6=Valeria |title = Iron Status of Vegans, Vegetarians and Pescatarians in Norway | journal = Biomolecules | date=2021 |volume = 11 | issue = 3 | page = 454 | doi date = 10.3390/biom11030454 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 on 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 and| Morework from]= Merriam-Webster {{webarchive| archive-url = https://web.archive.org/web/20100219015237/http://www.merriam-webster.com/medical/blaud%27s%20pill | archive-date =2010-02- 19 }}.February Merriam2010 | access-Webster.date Retrieved= on21 December 2012-12-21. }}</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.<ref>{{cite journal |last1 vauthors = Lynch|first1= SR, |last2=Cook|first2= JD | title = Interaction of vitamin C and iron. | journal = Annals of the New York Academy of Sciences | volume = 355 |year=1980| issue = 1 | pages = 32–44 | year = 1980 | pmid = 6940487 | doi = 10.1111/j.1749-6632.1980.tb21325.x|pmid=6940487 |bibcode s2cid =1980NYASA.355...32L 35848195 | citeseerx = 10.1.1.530.1906 |s2cid bibcode =35848195 1980NYASA.355...32L }}</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 |last1 vauthors = Seligman |first1=PaulPA, A. |last2=Moore |first2=GaryGM, M. |last3=Schleicher |first3=Rhoda B.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 }}</ref>
Another alternative is ''ferrous [[glycine]] [[sulfate]]'' or ''ferroglycine sulfate'', has less gastrointestinal side-effects than standard preparations such as iron fumarate.<ref>{{Citecite journal | last1vauthors = Aronstam | first1 = A. | last2 =, Aston | first2 = D.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 satisfactory effect.<ref>{{Citecite journal | last1vauthors = Hershko | first1 = C. | last2 =, Ianculovich | first2 = M. | last3 =, Souroujon | first3 = M. | title = Decreased Treatmenttreatment Failurefailure Ratesrates following Duodenalduodenal Releaserelease Ferrousferrous Glycineglycine Sulfatesulfate in Ironiron Deficiencydeficiency Anemiaanemia Associatedassociated with Autoimmuneautoimmune Gastritisgastritis and ''Helicobacter pylori'' Gastritis | doi = 10.1159/000101701gastritis | 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 mg/kg of body mass per day; i.e. for a 100 kg/220 lb man this is equal to a maximum dose of 200–600 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] {{webarchive| archive-url = https://web.archive.org/web/20120412155245/http://www.webmd.com/a-to-z-guides/iron-poisoning | archive-date =2012-04- 12 }}.December 2012 | work = Webmd.com (2012-09-27).| Retrieveddate on= 27 September 2012 | access-12-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=2017-09-18 }}</ref><ref>{{cite journal |url=http://chinesefms.com/doc/zhw/doc_zhw_xzzn/201104/P020110416418498436822.pdf|pmid=21464096|year=2011|last1 vauthors = Mowat|first1= C|last2=, Cole|first2= A|last3=, Windsor|first3= A|last4=, Ahmad|first4= T|last5=, Arnott|first5= I|last6=, Driscoll|first6= R|last7=, Mitton|first7= S|last8=, Orchard|first8= T|last9=, Rutter|first9= M|last10=, Younge|first10= L.|last11=, Lees|first11= C.|last12=, Ho|first12=G.-t.|last13= GT, Satsangi|first13= J.|last14=, Bloom S |first14 display-authors =S. 6 | 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 |journal url =Gut http://chinesefms.com/doc/zhw/doc_zhw_xzzn/201104/P020110416418498436822.pdf |display url-authorsstatus =8 dead |author15 access-date = 2012-08-08 | collaboration = IBD Section of the British Society of Gastroenterology | s2cid = 8269837 |url-status=dead| archive-url = https://web.archive.org/web/20130621085124/http://chinesefms.com/doc/zhw/doc_zhw_xzzn/201104/P020110416418498436822.pdf | archive-date = 2013-06-21|access-date=2012-08-08 }}</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 |last1 vauthors = Kumpf |first1=V.VJ | title = Parenteral iron supplementation | journal = Nutrition in Clinical Practice | volume = 11 | issue = 4 | pages =139–46 139–146 |year 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>{{cite web |url=https://www.medicines.org.uk/emc/medicine/24167 |title=Ferinject (ferric carboxymaltose) - Summary of Product Characteristics (SmPC) -| work = (eMC) |access-date=2017-03-07 |url-status=live |archive-url=https://web.archive.org/web/20170308045212/https://www.medicines.org.uk/emc/medicine/24167 |archive-date=2017-03-08 | publisher = Datapharm }}</ref>
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. post partum, post operatively, 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">{{Citecite journal |last1 vauthors = Gordon |first1=MorrisM, |last2=Sinopoulou |first2=VassilikiV, |last3=Iheozor-Ejiofor |first3=ZipporahZ, |last4=Iqbal |first4=TariqT, |last5=Allen |first5=PatrickP, |last6=Hoque |first6=SamiS, |last7=Engineer |first7=JainaJ, |last8=Akobeng AK |first8=Anthony Kdisplay-authors |date=2021 6 | 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 |pmc=8092475 |pmid=33471939}}</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 |last1 vauthors = Moore |first1=RRA, Andrew |last2=Gaskell |first2=Helen|last3=H, Rose |first3=PeterP, |last4=Allan |first4=JonathanJ | 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 |year date = September 2011 | pmid = 21942989 | pmc = 3206450 | doi = 10.1186/1471-2326-11-4 }}</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 | doivauthors = 10.1093/eurheartj/ehw128Ponikowski |P, pmid=27206819Voors |AA, volume=37Anker |SD, issue=27Bueno |H, title=2016Cleland ESCJG, GuidelinesCoats forAJ, theFalk diagnosisV, andGonzález-Juanatey treatmentJR, ofHarjola acuteVP, andJankowska chronicEA, heartJessup failureM, |Linde journal=EuropeanC, HeartNihoyannopoulos JournalP, |Parissis pages=2129–2200|JT, year=2016Pieske |B, last1=PonikowskiRiley |JP, first1=PiotrRosano |GM, last2=VoorsRuilope |LM, first2=AdriaanRuschitzka A.F, |Rutten last3=AnkerFH, |van first3=Stefander D.Meer P | last4display-authors =Bueno 6 | first4title =Héctor |2016 last5=ClelandESC |Guidelines first5=Johnfor G.the F.diagnosis |and last6=Coatstreatment |of first6=Andrewacute J.and S.chronic |heart last7=Falkfailure: |The first7=VolkmarTask |Force last8=González-Juanateyfor |the first8=Josédiagnosis Ramónand |treatment last9=Harjolaof |acute first9=Veli-Pekkaand |chronic last10=Jankowskaheart |failure first10=Ewaof A.the |European last11=JessupSociety |of first11=MariellCardiology |(ESC)Developed last12=Lindewith |the first12=Ceciliaspecial |contribution last13=Nihoyannopoulosof |the first13=PetrosHeart |Failure last14=ParissisAssociation |(HFA) first14=Johnof T.the ESC | last15journal =Pieske |European first15=BurkertHeart Journal | last16=Rileyvolume | first16=Jillian P.37 | last17=Rosanoissue | first17=Giuseppe M. C.27 | last18=Ruilope |pages first18=Luis M.2129–2200 | last19date =Ruschitzka |July first19=Frank2016 | last20pmid =Rutten 27206819 | first20doi =Frans H10.1093/eurheartj/ehw128 | last21=Vanauthor22 Der Meer | first21=Peter | author22=ESC Scientific Document Group | doi-access = free }}</ref><ref>{{cite journal | doivauthors = 10.1093/ecco-jcc/jju009Dignass |AU, pmid=25518052Gasche |C, volume=9Bettenworth |D, issue=3Birgegård |G, title=EuropeanDanese ConsensusS, onGisbert theJP, DiagnosisGomollon andF, ManagementIqbal ofT, IronKatsanos DeficiencyK, andKoutroubakis AnaemiaI, inMagro InflammatoryF, BowelSavoye DiseasesG, |Stein journal=JournalJ, ofVavricka Crohn's and ColitisS | pages=211–222|display-authors year=2015 6 | last1title =Dignass |European first1=Axelconsensus U.on |the last2=Gaschediagnosis |and first2=Christophmanagement |of last3=Bettenworthiron |deficiency first3=Dominikand |anaemia last4=Birgegårdin |inflammatory first4=Gunnarbowel diseases | last5=Danese |journal first5=Silvio |Journal last6=Gisbertof |Crohn's first6=Javier& P.Colitis | last7volume =Gomollon 9 | first7=Fernandoissue | last8=Iqbal | first8=Tariq3 | last9=Katsanos |pages first9=Konstantinos | last10=Koutroubakis211–222 | first10=Ioannisdate | last11=Magro |March first11=Fernando2015 | last12=Savoyepmid | first12=Guillaume | last13=Stein25518052 | first13=Jürgendoi | last14=Vavricka | first14=Stephan10.1093/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">{{Citecite journal |last1 vauthors = O'Lone |first1=EmmaEL, L |last2=Hodson |first2=ElisabethEM, M |last3=Nistor |first3=IonutI, |last4=Bolignano |first4=DavideD, |last5=Webster |first5=AngelaAC, C |last6=Craig |first6=Jonathan CJC |date=2019 |editor-last=Cochranetitle Kidney= and Transplant Group |title=Parenteral versus oral iron therapy for adults and children with chronic kidney disease | journal = The Cochrane Database of Systematic Reviews | volume = 2 | issue = 2 | pages = CD007857 |language date =en February 2019 | pmid = 30790278 | pmc = 6384096 | doi = 10.1002/14651858.CD007857.pub3 |pmc=6384096 |pmidcollaboration =30790278 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 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 type of iron therapy administration affects the risk of death from any cause, including cardiovascular, nor 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 different molecules to limit this. This has included [[dextrans]], [[sucrose]], carboxymaltose and more recently Isomaltoside 1000.{{citation needed|date=July 2015}}
One formulation of parenteral iron is ''iron dextran'' which covers the old high molecular weight (trade name ''DexFerrum'') and the much safer low molecular iron dextrans (tradenames including Cosmofer and Infed).<ref>{{cite journal |last1 vauthors = Chertow |first1=GlennGM, M. |last2=Mason |first2=PhillipPD, D. |last3=Vaage-Nilsen |first3=OddO, |last4=Ahlmén J |first4=Jarl |title = On the relative safety of parenteral iron formulations | journal = Nephrology, Dialysis, Transplantation | volume = 19 | issue = 6 | pages =1571–5 1571–1575 |year date = June 2004 | pmid = 15150356 | doi = 10.1093/ndt/gfh185 | doi-access = free }}</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] {{webarchive| 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 2011-10-01 }}| inwork = [[FASS (drug formulary)]], translated| fromlanguage = 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 mg on each occasion according to the SPC, but it has been given in doses of 500 mg. Doses can be given up to 3 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=2017-03-07 |url-status=live |archive-url=https://web.archive.org/web/20170308044906/https://www.medicines.org.uk/emc/medicine/24168 |archive-date=2017-03-08 }}</ref>
''Iron carboxymaltose'' is marketed as ''Ferinject'', ''Injectafer'', and ''Iroprem'' in various countries.<ref name=InjectaferSumm>{{cite web|title=Summary review: Application number 203565Orig1s000 by Luitpold Pharmaceuticals, Inc.|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203565Orig1s000SumR.pdf|publisher=FDA|date=July 24, 2013|url-status=live|archive-url=https://web.archive.org/web/20170228171255/http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/203565Orig1s000SumR.pdf|archive-date=February 28, 2017}}</ref><ref name="CançadoMuñoz2011"/> The most common side effects are [[headaches]] which occur in 3.3%, and hypophosphatemia, which occurs in more than 35%.<ref>[{{cite web | url = http://www.medicines.org.uk/emc/medicine/24167/SPC#UNDESIRABLE_EFFECTS | title = Ferinject (ferric carboxymaltose) – Summary of Product Characteristics (SPC) –| work = (eMC)] {{webarchive| archive-url = https://web.archive.org/web/20140309172330/http://www.medicines.org.uk/emc/medicine/24167/SPC | archive-date = 9 April 2014-03-09 }}. Medicines.org.uk. Retrieved on 2012-12-21.</ref><ref>{{cite web|title=Injectafer US label|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203565s000lbl.pdf|publisher=FDA|date=July 2013|url-status=live|archive-url=https://web.archive.org/web/20170406111606/https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/203565s000lbl.pdf|archive-date=2017-04-06}} See [http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203565 FDA index page for NDA 203565] {{webarchive|url=https://web.archive.org/web/20170407145738/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=203565 |date=2017-04-07 }} for updates and further information.</ref>
''Iron Isomaltoside 1000'' (Trade name ''Monofer'') is a newer 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 mg/kg in a single visit – no upper dose limit. This formulation has the benefit of giving a full iron correction in a single visit.<ref>{{cite journal |last1 vauthors = Jahn |first1=MarkusMR, R. |last2=Andreasen |first2=HansHB, B. |last3=Fütterer |first3=SörenS, |last4=Nawroth |first4=ThomasT, |last5=Schünemann |first5=VolkerV, |last6=Kolb |first6=UteU, |last7=Hofmeister |first7=WolfgangW, |last8=Muñoz |first8=ManuelM, |last9=Bock |first9=KlausK, |last10=Meldal |first10=MortenM, |last11=Langguth P |first11 display-authors =Peter 6 | 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 =480–91 480–491 |year date = August 2011 | pmid = 21439379 | doi = 10.1016/j.ejpb.2011.03.016 }}</ref><ref name="CançadoMuñoz2011">{{cite journal |last1=Cançado |first1vauthors =Rodolfo DelfiniCançado RD, |last2=Muñoz |first2=ManuelM | title = Intravenous iron therapy: how far have we come? | journal = Revista Brasileira deDe Hematologia eE Hemoterapia | volume = 33 | issue = 6 | pages =461–9 461–469 | year = 2011 | pmid = 23049364 | pmc = 3459360 | doi = 10.5581/1516-8484.20110123 }}</ref>
[[Ferric maltol]], marketed as ''Accrufer'' and ''Ferracru,'' is available in oral and IV 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" />
Follow-up is needed to ensure compliance and to detect adequate response to therapy. The interval of follow up can widely depend on both the method of administration, and the underlying pathology. For parenteral irons it is recommended that there be a period of 4 weeks before repeating blood test to allow the body to utilise the iron.<ref name="medicines.org.uk"/> For oral iron, this can take considerably longer, so waiting three months may be appropriate.
== See also ==
* [[Geritol]]
* [[Human iron metabolism]]
* [[Lucky iron fish]]
== References ==
{{reflist}}
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