Oral_iron

Oral Iron Supplementation: Oral Iron Supplementation: ReviewReview

Dr. KISHORE Dr. KISHORE CHANDKICHANDKI

Kids’ Care Clinic,Kids’ Care Clinic,

Indore (M.P.) INDIAIndore (M.P.) INDIA

Oral Iron Therapy in ChildrenOral Iron Therapy in Children

Cost effectiveCost effective

SafeSafe

ConvenientConvenient

Well toleratedWell tolerated

Corrects anemia just as rapidly & completely as Corrects anemia just as rapidly & completely as parenteral iron in most casesparenteral iron in most cases

Preferred to intravenous therapyPreferred to intravenous therapy

Ideal modeIdeal mode of treatment for IDA of treatment for IDA

IAP Textbook of Pediatrics, 3IAP Textbook of Pediatrics, 3rdrd Ed, 2006, Basic & Clinical Pharmacology, Katzung, 10 Ed, 2006, Basic & Clinical Pharmacology, Katzung, 10 thth Ed Ed

Principles of TreatmentPrinciples of Treatment

Use oral Use oral ironiron

ReplaceReplaceiron deficitiron deficitin totalin total

Establish Establish

& treat & treat

the causethe cause

Iron PreparationsIron Preparations

InorganicFerrous sulphate

Ferrous fumarate

Ferric ammonium citrate

OrganicFerric Polymaltose

Element Carbonyl Iron

TechnologicalFerrous Ascorbate

Chelated Iron

Ferrous bis glycinate

Iron AbsorptionIron AbsorptionPrimarily Primarily duodenumduodenum (& proximal jejunum) (& proximal jejunum)Hem ironHem iron 20-40%, AA directly without carrier, 20-40%, AA directly without carrier, with HCl with HClNon hemNon hem (plant) 10% (plant) 10% Increased in IDA to ▲30%Increased in IDA to ▲30%Mechanisms Mechanisms of absorption:of absorption:By active absorptionBy active absorption (DMT1) mucosal & ferroportin1 (basal) (DMT1) mucosal & ferroportin1 (basal)▲ ▲ Anemia & hypoxemia & Erythropoiesis, hereditary hemochromatosis, Anemia & hypoxemia & Erythropoiesis, hereditary hemochromatosis, iron stores but less affected with plasma iron & ▼Inflammation & iron stores but less affected with plasma iron & ▼Inflammation & malignancymalignancyWhat is the elation between Hepcidin & ferroportin? Anemia of CDWhat is the elation between Hepcidin & ferroportin? Anemia of CDEnters mucosal cells as Ferrous ►eitherEnters mucosal cells as Ferrous ►either A. Ferric ►Apoferritin ►ferritin (Mucosal block) = Ferritin curtainA. Ferric ►Apoferritin ►ferritin (Mucosal block) = Ferritin curtain B. Transported to serum as ferrousB. Transported to serum as ferrousWhat are the factors that govern these processes? What are the factors that govern these processes? About 1 mg is absorbed dailyAbout 1 mg is absorbed daily

Passive transportPassive transport with AA or when in large amounts (e.g. toxicity) with AA or when in large amounts (e.g. toxicity)

Iron Absorption ParametersIron Absorption Parameters

Stability in gastric acidsStability in gastric acids

Form administeredForm administered

Status of patient’s iron storesStatus of patient’s iron stores

DoseDose

oElemental ironElemental iron

oBioavailabilityBioavailability

oPhytate inhibitionPhytate inhibition

Iron Absorption ParametersIron Absorption Parameters

Elemental ironElemental iron

Amount of iron in a supplement that Amount of iron in a supplement that is is availableavailable for absorption for absorption

BioavailabilityBioavailability

Fraction of the elemental iron that Fraction of the elemental iron that reachesreaches the systemic circulation the systemic circulation

Phytate inhibitionPhytate inhibition

ReducingReducing the the absorptionabsorption of iron by of iron by 15-fold15-fold

Elemental Content Vs Elemental Content Vs BioavailabilityBioavailability

Ferrous sulphateFerrous sulphate 20%20% 100% Standard100% Standard

Ferrous bis glycinateFerrous bis glycinate 2020 ?199?199

Ferrous succinateFerrous succinate 3535 123123

IPCIPC 3434 ?~FS?~FS

Ferrous fumarateFerrous fumarate 3333 101101

Ferrous glycine sulphateFerrous glycine sulphate 2323 101101

Ferrous ascorbateFerrous ascorbate 1414 9797

Ferrous pyrophosphateFerrous pyrophosphate 2525 8989

Ferric ammonium citrateFerric ammonium citrate 1818 7474

Ferrous gluconateFerrous gluconate 1212 8989

Carbonyl IronCarbonyl Iron >90>90 7070

Sod. Feredetate (Ferric)Sod. Feredetate (Ferric) 1414 ??

Colloidal IronColloidal Iron 5050 ??

Status of Iron StoresStatus of Iron StoresIn persons with normal stores 10% of an oral dose is In persons with normal stores 10% of an oral dose is absorbed, this is increased to 20%-30% in persons with absorbed, this is increased to 20%-30% in persons with inadequate iron storesinadequate iron storesPeak reticulocyte count experienced on days 5–10 after Peak reticulocyte count experienced on days 5–10 after initiation of iron therapy. Following this, Hb rises on initiation of iron therapy. Following this, Hb rises on average by 0.25–0.4 g/dL/day or hematocrit rises 1%/day average by 0.25–0.4 g/dL/day or hematocrit rises 1%/day during first 7–10 days. during first 7–10 days. ThereafterThereafter, , Hb rises more slowlyHb rises more slowly: : 0.1–0.15 g/dL/day.0.1–0.15 g/dL/day.As the hemoglobin level rises, As the hemoglobin level rises, iron absorption declinesiron absorption declines and the rate of RBC production (which was up to 3 times and the rate of RBC production (which was up to 3 times the normal) falls, the normal) falls, regardless ofregardless of the oral iron the oral iron intakeintake. . Therefore, the dosage can be reduced as the hemoglobin Therefore, the dosage can be reduced as the hemoglobin rises to level above 11 to 12 gm%. This will help rises to level above 11 to 12 gm%. This will help guarantee patient compliance for a therapy that must guarantee patient compliance for a therapy that must continue for several months.continue for several months.

Harrison's Principles of Internal Medicine, 14th Ed.,1998, Vol. 1, Pg 642Harrison's Principles of Internal Medicine, 14th Ed.,1998, Vol. 1, Pg 642

Review of Preparations: Ferrous Review of Preparations: Ferrous SaltsSalts

Preferred over ferric salt preparations.Preferred over ferric salt preparations.Most Most economicaleconomicalFerrous sulfate (FS): is commonly used for tablet Ferrous sulfate (FS): is commonly used for tablet preparations. However, liquid formulations of the salt are preparations. However, liquid formulations of the salt are only available as elixirs in sorbitol base as syrup only available as elixirs in sorbitol base as syrup preparations are poorly stable (the salt is easily preparations are poorly stable (the salt is easily oxidizable in moist environment, oxidizable in moist environment, unpleasant tasteunpleasant taste) which ) which negates the cost advantage. negates the cost advantage. Ferrous Fumarate (FF): similar efficacy & GI tolerance to Ferrous Fumarate (FF): similar efficacy & GI tolerance to FS, is environmentally more stable and is almost FS, is environmentally more stable and is almost tastelesstasteless. Ferrous fumarate is less soluble than ferrous . Ferrous fumarate is less soluble than ferrous sulfate in water but is soluble in dilute acid such as sulfate in water but is soluble in dilute acid such as gastric juice. It does not precipitate proteins and does not gastric juice. It does not precipitate proteins and does not interfere with the proteolytic or diastatic activities of the interfere with the proteolytic or diastatic activities of the digestive systemdigestive system

Ferrous SaltsFerrous SaltsGood bioavailability, but decreases markedly in the Good bioavailability, but decreases markedly in the presence of dietary inhibitors like phytates, tannic acid presence of dietary inhibitors like phytates, tannic acid etc., hence cannot be added to other foods/milk/fortified etc., hence cannot be added to other foods/milk/fortified formulasformulasSalty astringent Salty astringent tastetasteGastrointestinalGastrointestinal side effects (~23 %) side effects (~23 %) Teeth Teeth are known to be are known to be stainedstained with liquid preparations if with liquid preparations if the drops are not placed carefully at the back of the the drops are not placed carefully at the back of the tongue tongue Any over dosage of the salt can easily override the Any over dosage of the salt can easily override the ‘mucosal barrier’ to cause acute ‘mucosal barrier’ to cause acute toxicitytoxicity

Ferric SaltsFerric SaltsDietary Fe+3 form is converted to the Fe+2 form in the Dietary Fe+3 form is converted to the Fe+2 form in the stomach. This reduction is promoted by the presence of stomach. This reduction is promoted by the presence of H+ and dietary ascorbic acid. The great advantage of this H+ and dietary ascorbic acid. The great advantage of this conversion is that the ferrous form (as compared to the conversion is that the ferrous form (as compared to the ferric form) is much more easily released from the ferric form) is much more easily released from the organic ligands to which it is bound and stays soluble. organic ligands to which it is bound and stays soluble. Ferric iron precipitates at pH >3 (as found in the Ferric iron precipitates at pH >3 (as found in the duodenum) and is not available for absorption from such duodenum) and is not available for absorption from such precipitates. Ferrous iron remains soluble up to pH precipitates. Ferrous iron remains soluble up to pH values of about 7.5 and is available for absorption.values of about 7.5 and is available for absorption. Traditionally not been preferred over ferrous, bio-Traditionally not been preferred over ferrous, bio-availability is 3 to 4 times lessavailability is 3 to 4 times lessIn adults 100 mg of ferrous sulfate iron/ day In adults 100 mg of ferrous sulfate iron/ day 400 to 400 to 1000 mg of ferric iron/day for same therapeutic effect1000 mg of ferric iron/day for same therapeutic effectPoor poisoning potentialPoor poisoning potential given the limited reducing given the limited reducing ability of the gastric contentsability of the gastric contentsOther properties similar to ferrous saltsOther properties similar to ferrous salts

Iron Amino-acid ChelatesIron Amino-acid ChelatesConjugates of the ferrous or ferric ion with amino-acidsConjugates of the ferrous or ferric ion with amino-acidsFerrous bis-glycinate (20% elemental iron), ferric Ferrous bis-glycinate (20% elemental iron), ferric trisglycinate and ferrous glycine sulphate (FGS)trisglycinate and ferrous glycine sulphate (FGS)FBG: Two molecules of the amino acid glycine are FBG: Two molecules of the amino acid glycine are bound covalently to a molecule of iron. bound covalently to a molecule of iron. They have They have no effect on the colorno effect on the color or taste of food or taste of food productsproductsMain advantage: Main advantage: relatively high bioavailability in the relatively high bioavailability in the presence of dietary inhibitorspresence of dietary inhibitors. Chelates prevent iron from . Chelates prevent iron from binding to inhibitors in food or precipitating as insoluble binding to inhibitors in food or precipitating as insoluble ferric hydroxide in the pH of the small intestineferric hydroxide in the pH of the small intestineRise of HbRise of Hb with FGS Vs FS is with FGS Vs FS is equivalentequivalentCostlierCostlier

Advances in Pediatrics, Dutta, Anupam Sachdev, 1Advances in Pediatrics, Dutta, Anupam Sachdev, 1stst Ed, 2007 Ed, 2007

Iron Polymaltose Complex (IPC)Iron Polymaltose Complex (IPC)Contains non-ionic iron and polymaltose in a stable Contains non-ionic iron and polymaltose in a stable complexcomplexBioavailability similar to FSBioavailability similar to FSAbsorption Absorption not affected by foodnot affected by food or milk or milkTo date there are no reports of any interactions with To date there are no reports of any interactions with foods or medicinesfoods or medicinesDoes Does not stain teethnot stain teethBetter absorbed, Better absorbed, lesser GI sidelesser GI side effects effectsImprovement in Improvement in Hb level is lessHb level is less w.r.t. other preparations w.r.t. other preparationsIntoxication rareIntoxication rare: Iron of IPC is absorbed in the intestine : Iron of IPC is absorbed in the intestine through a self-limiting competitive interchange of ligands, through a self-limiting competitive interchange of ligands, so that the intestinal transport system is saturated in so that the intestinal transport system is saturated in case of over dosagecase of over dosage

Advances in Pediatrics, Dutta, Anupam Sachdev, 1Advances in Pediatrics, Dutta, Anupam Sachdev, 1stst Ed, 2007 Ed, 2007

Carbonyl IronCarbonyl IronSmall particle preparation of highly purified Small particle preparation of highly purified metallic ironmetallic iron‘‘Carbonyl’ describes the process of manufacture of the Carbonyl’ describes the process of manufacture of the iron particles (from iron pentacarbonyl gas)iron particles (from iron pentacarbonyl gas)Given the Given the small particle sizesmall particle size (<5 (<5 m) the stomach acid m) the stomach acid solubilizes this iron. In the process of this solubilization solubilizes this iron. In the process of this solubilization H+ ions are consumed thereby increasing the pH. Also, as H+ ions are consumed thereby increasing the pH. Also, as a result the absorption of iron is a result the absorption of iron is slow slow (permitting (permitting continued release for 1 to 2 days) and self limited by the continued release for 1 to 2 days) and self limited by the rate of acid secretion by the stomach mucosarate of acid secretion by the stomach mucosaAdvantages include Advantages include lack of change in colorlack of change in color or taste of or taste of the foodstuff the foodstuff Bioavailability is high, about 70% that of FSBioavailability is high, about 70% that of FSLesser GI side effects claimed: not confirmedLesser GI side effects claimed: not confirmedMuch Much less toxicless toxic than ionized forms of iron than ionized forms of iron

Colloidal IronColloidal IronColloidal ferric hydroxide which provides the Colloidal ferric hydroxide which provides the highest highest amount of elemental ironamount of elemental iron (50%) (50%)Not much data available regarding bioavailabilityNot much data available regarding bioavailabilityDrug Interactions : Absorption of iron may be affected by Drug Interactions : Absorption of iron may be affected by concurrent administration of antacids. On concomitant concurrent administration of antacids. On concomitant administration of iron and tetracycline the absorption of administration of iron and tetracycline the absorption of both the drugs is markedly reduced leading to diminished both the drugs is markedly reduced leading to diminished therapeutic effectivenesstherapeutic effectivenessComparable rise in HbComparable rise in Hb level level

Indian Journal of Pediatrics 1989 ; 56 : 105-107Indian Journal of Pediatrics 1989 ; 56 : 105-107

Heme IronHeme IronHemoglobin as a source of iron was promoted on the Hemoglobin as a source of iron was promoted on the basis of the high bioavailability of heme ironbasis of the high bioavailability of heme ironIron content of hemoglobin is 0.34 %. As a result 300 mg Iron content of hemoglobin is 0.34 %. As a result 300 mg of hemoglobin is required to deliver 1 mg of elemental of hemoglobin is required to deliver 1 mg of elemental iron which leads to large volumes and inhibitory costs.iron which leads to large volumes and inhibitory costs.Do not offer additional advantageDo not offer additional advantage over the simple over the simple ferrous salts.ferrous salts.

IAP Textbook of Pediatrics, 3IAP Textbook of Pediatrics, 3rdrd Ed, 2006 Ed, 2006

Ferrous AscorbateFerrous AscorbateSynthetic moleculeSynthetic molecule of ascorbic acid & iron of ascorbic acid & ironAscorbic acid enhances iron absorptionAscorbic acid enhances iron absorptionAscorbic acid reduces ferric iron to ferrous iron Ascorbic acid reduces ferric iron to ferrous iron which remains soluble even at neutral pHwhich remains soluble even at neutral pH

Comparison of SaltsComparison of Salts

SaltSalt GI Side GI Side EffectsEffects

Teeth Teeth stainingstaining

Food/Drug Food/Drug interactioninteraction

Poisoning Poisoning PotentialPotential

Ferrous Ferrous sulphatesulphate

~23%~23% ++ ++++++ ++++++

Ferrous Ferrous FumarateFumarate

++ ++++ ++

Amino Acid Amino Acid ChelatesChelates

LessLess -- -- ++

IPCIPC LessLess -- -- NilNil

CarbonylCarbonyl ?Less?Less -- -- NilNil

ColloidalColloidal LessLess ++ ++ ??

Treatment of IDATreatment of IDAFerrousFerrous sulphate remains the sulphate remains the mainstay mainstay Generally, the toxicity is proportional to the Generally, the toxicity is proportional to the amount of iron available for absorption. If the amount of iron available for absorption. If the quantity of iron in the test dose is decreased, the quantity of iron in the test dose is decreased, the percentage of the test dose absorbed is increased, percentage of the test dose absorbed is increased, but the quantity of iron absorbed is diminishedbut the quantity of iron absorbed is diminishedMultiple preparations available, Multiple preparations available, all are generally all are generally absorbed well and are effectiveabsorbed well and are effective in treatment in treatment

Harrison’s Principles of Internal Medicine, 17Harrison’s Principles of Internal Medicine, 17 thth Edition. Edition.

Treatment of IDATreatment of IDASome contain Some contain 'absorption enhancing'absorption enhancing' substances ' substances such as amino acids & ascorbic acid.such as amino acids & ascorbic acid.NoNo evidence shows that addition of any trace evidence shows that addition of any trace metal, vitamin or other hematenic substance metal, vitamin or other hematenic substance significantlysignificantly increases the response to simple increases the response to simple ferrous saltsferrous saltsOthers are advertised as delayed-released Others are advertised as delayed-released formulations aimed at prolonging iron absorption formulations aimed at prolonging iron absorption over several hours. All these are expensive. over several hours. All these are expensive. Moreover, attempts to enhance absorption can Moreover, attempts to enhance absorption can increase the incidence of GI side effects.increase the incidence of GI side effects.

Nelson Textbook of pediatrics, 18Nelson Textbook of pediatrics, 18thth Ed, 2008 Ed, 2008

Time after Iron Time after Iron AdministrationAdministration

ResponseResponse

12-24 hr 12-24 hr Subjective improvementSubjective improvement; ; decreased irritability, decreased irritability, increased appetiteincreased appetite

36-48 hr36-48 hr Initial bone marrow responseInitial bone marrow response

48-72 hr 48-72 hr Reticulocytosis, peak at 5 -7 Reticulocytosis, peak at 5 -7 daysdays

4-30 days4-30 days Increase in hemoglobin levelIncrease in hemoglobin level

1-3 months1-3 months Repletion of storesRepletion of stores

Response to Iron TherapyResponse to Iron Therapy


Pica, pagophagia, amylophagiaPica, pagophagia, amylophagia (laundry starch/ (laundry starch/ raw rice) and non-specific symptoms disappear raw rice) and non-specific symptoms disappear within within one weekone weekOf the epithelial lesions, those affecting tongue Of the epithelial lesions, those affecting tongue and nails are most responsive to treatment. After and nails are most responsive to treatment. After 1-2 weeks of therapy, small filiform papillae are 1-2 weeks of therapy, small filiform papillae are seen on the tongueseen on the tongueBy 3 month, the tongue is usually normalBy 3 month, the tongue is usually normalKoilonychiaKoilonychia usually disappears within usually disappears within 3-6 3-6 monthsmonthsA A positive hematological responsepositive hematological response has been has been defined as rise of Hb defined as rise of Hb 0.1 g/dL daily0.1 g/dL daily (up to 0.4 g) (up to 0.4 g)

Response to Iron TherapyResponse to Iron Therapy

J. K. Science Vol. 3 No.4. October-December 2001J. K. Science Vol. 3 No.4. October-December 2001

Suboptimal Response: CausesSuboptimal Response: Causes

Poor Poor compliancecompliance (failure or irregular administration): (failure or irregular administration):

major problemmajor problemDiscontinuationDiscontinuation of Tx after initial 3 to 4 weeks because of Tx after initial 3 to 4 weeks because

of feeling of well being & disappearance of symptoms of of feeling of well being & disappearance of symptoms of

anemiaanemiaSub therapeutic Sub therapeutic dosedose (< 3-6 mg/kg/d) (< 3-6 mg/kg/d)Poorly absorbed Poorly absorbed preparationpreparation, e.g. enteric coated tab? , e.g. enteric coated tab? Iron administration soon after intake of milk Iron administration soon after intake of milk

(phosphates) or cereals (phytates)(phosphates) or cereals (phytates)Persistent Persistent blood lossblood loss (occult or frank), with the patient (occult or frank), with the patient

losing iron as fast as it is replaced: milk allergy, polyps, losing iron as fast as it is replaced: milk allergy, polyps,

ulcer disease, esophagitis, menorrhagiaulcer disease, esophagitis, menorrhagia

The Short Textbook of Pediatrics, Suraj Gupte, 9th Ed,2001Pg 412The Short Textbook of Pediatrics, Suraj Gupte, 9th Ed,2001Pg 412

Suboptimal ResponseSuboptimal Response

Incorrect diagnosisIncorrect diagnosis of IDA in thalassemia, lead of IDA in thalassemia, lead

poisoning or anemia of chronic infectionpoisoning or anemia of chronic infectionCoexistent diseaseCoexistent disease that interferes with absorption or that interferes with absorption or

utilization of iron (e.g., infection, IBD, malignancy, hepatic utilization of iron (e.g., infection, IBD, malignancy, hepatic

or renal disease, or concomitant deficiencies of, for or renal disease, or concomitant deficiencies of, for

instance, vitamin B12, folic acid, thyroid, associated lead instance, vitamin B12, folic acid, thyroid, associated lead

poisoning)poisoning)Impaired GI absorptionImpaired GI absorption (e.g., Celiac disease, giardiasis, (e.g., Celiac disease, giardiasis,

H. Pylori infection, autoimmune gastritis, concurrent H. Pylori infection, autoimmune gastritis, concurrent

administration of large amounts of antacids, which bind administration of large amounts of antacids, which bind

iron and H2RA)iron and H2RA)

Ghai Essential Pediatrics, 7Ghai Essential Pediatrics, 7thth Ed, 2009, Ghai, Kaul, Bagga Ed, 2009, Ghai, Kaul, Bagga

Iron absorption may be decreased by antacids or Iron absorption may be decreased by antacids or supplements containing aluminum, supplements containing aluminum, magnesiummagnesium, , calciumcalcium, , zinczinc, PPI, & H2 RA, PPI, & H2 RAIron may decrease the absorption of bisphosphonates, Iron may decrease the absorption of bisphosphonates, tetracyclinestetracyclines, levodopa, methyldopa, levothyroxine and , levodopa, methyldopa, levothyroxine and penicillamine. (Space administration apart by at least 2 penicillamine. (Space administration apart by at least 2 hours)hours)Absorption of Absorption of quinolonesquinolones may be may be ed due to formation of ed due to formation of ferric-quinolone complexferric-quinolone complexResponse to iron therapy may be delayed in patients Response to iron therapy may be delayed in patients receiving chloramphenicolreceiving chloramphenicolConcurrent administration of Concurrent administration of 200 mg vitamin C per 30 200 mg vitamin C per 30 mg elemental iron mg elemental iron es the absorptiones the absorption

InteractionInteraction

The Harriet Lane Handbook, 18th EditionThe Harriet Lane Handbook, 18th Edition

Phytates in Phytates in cerealscereals & oxalates ( & oxalates (vegetablesvegetables), high ), high phosphate in phosphate in cow's milkcow's milk (+casein) & excess of zinc also (+casein) & excess of zinc also reduce absorption. Thus children who take only milk & reduce absorption. Thus children who take only milk & rice tend to have iron deficiencyrice tend to have iron deficiencyCalcium saltsCalcium salts (carbonates/oxalates) & (carbonates/oxalates) & eggseggs in the diet in the diet inhibit iron absorptioninhibit iron absorptionTannic acid present in Tannic acid present in tea & coffeetea & coffee, forms complexes , forms complexes with iron salts & inhibits absorptionwith iron salts & inhibits absorptionLactose, ascorbic acid, Lactose, ascorbic acid, fruit juicesfruit juices and certain amino and certain amino acids such as cystine, lysine & histidine enhance iron acids such as cystine, lysine & histidine enhance iron absorptionabsorptionHClHCl of the gastric juice facilitates iron absorption from of the gastric juice facilitates iron absorption from the ferric complexes, preventing its precipitation by the ferric complexes, preventing its precipitation by phosphates & maintaining iron in ferrous form phosphates & maintaining iron in ferrous form


Nutrition & Child Development, Dr. K E Elizabeth, 2nd Ed, 2002, Pg 103Nutrition & Child Development, Dr. K E Elizabeth, 2nd Ed, 2002, Pg 103

Acid medium & Acid medium & cobaltcobalt increase iron absorption. increase iron absorption.Consumption of lemon juice, fruit juice & Consumption of lemon juice, fruit juice & curd with foodcurd with food will increase absorption due to presence of vitamin C.will increase absorption due to presence of vitamin C.Heme iron from animal source (from myoglobin and red Heme iron from animal source (from myoglobin and red cells in red meats) is better absorbed.cells in red meats) is better absorbed.Ascorbic acid & meat facilitate the absorption of Ascorbic acid & meat facilitate the absorption of nonheme iron. Ascorbate forms complexes with &/or nonheme iron. Ascorbate forms complexes with &/or reduces ferric to ferrous iron. Meat facilitates the reduces ferric to ferrous iron. Meat facilitates the absorption of iron by stimulating production of gastric absorption of iron by stimulating production of gastric acid; other effects also may be involved.acid; other effects also may be involved.

Iron supplementation reduce cough induced by ACE Iron supplementation reduce cough induced by ACE inhibitors. inhibitors. (Ref. Goodman & Gilman's The Pharmacological Basis of Therapeutics)(Ref. Goodman & Gilman's The Pharmacological Basis of Therapeutics)


Nutrition & Child Development, Dr. K E Elizabeth, 2nd Ed, 2002, Pg 103Nutrition & Child Development, Dr. K E Elizabeth, 2nd Ed, 2002, Pg 103

Gastrointestinal distressGastrointestinal distress is the most prominent . is the most prominent . Abdominal pain, nausea, vomiting, or constipation may Abdominal pain, nausea, vomiting, or constipation may lead to noncompliance. Although small doses of iron or lead to noncompliance. Although small doses of iron or iron preparations with delayed release may help iron preparations with delayed release may help somewhat, the gastrointestinal side effects are a major somewhat, the gastrointestinal side effects are a major impediment to the effective treatment of a number of impediment to the effective treatment of a number of patientspatients

GI side effects are more common in adults and GI side effects are more common in adults and adolescents and are reported to occur in adolescents and are reported to occur in 15-20 %15-20 % patients. To overcome this side effect various measures patients. To overcome this side effect various measures suggested include administration after meals and at bed suggested include administration after meals and at bed time. Decreased intestinal motility during sleep may time. Decreased intestinal motility during sleep may improve absorptionimprove absorption

Harrison’s Principles of Internal Medicine, 17Harrison’s Principles of Internal Medicine, 17 thth Edition. Edition.

Side EffectsSide Effects

Temporary staining of teeth & tongue Temporary staining of teeth & tongue with some with some preparations: Can be avoided by correctly placing the preparations: Can be avoided by correctly placing the drops at the back of the tongue or drinking through straw. drops at the back of the tongue or drinking through straw. Or rinsing the mouth or brushing the teeth after taking the Or rinsing the mouth or brushing the teeth after taking the medicine.medicine.

Black stools: Black stools: The iron in the stools and supplement may The iron in the stools and supplement may stain clothing.stain clothing. Common, but may obscure the diagnosis Common, but may obscure the diagnosis of continued GI blood loss! of continued GI blood loss!

Rudolph’s Pediatrics, 21Rudolph’s Pediatrics, 21stst Ed, 2002, Pg 1528 Ed, 2002, Pg 1528


Intolerance to oral preparations of iron primarily is a Intolerance to oral preparations of iron primarily is a function of the amount of soluble iron in the upper GI function of the amount of soluble iron in the upper GI tract & of tract & of psychologicalpsychological factors. factors.

A good policy is to initiate therapy at a small dosage, to A good policy is to initiate therapy at a small dosage, to demonstrate freedom from symptoms at that level, and demonstrate freedom from symptoms at that level, and then gradually to increase the dosage to that desired.then gradually to increase the dosage to that desired.

Goodman & Gilman's The Pharmacological Basis of Therapeutics, 2008Goodman & Gilman's The Pharmacological Basis of Therapeutics, 2008


Hypersensitivity to iron salts or any componentHypersensitivity to iron salts or any component

Peptic ulcer diseasePeptic ulcer disease

Ulcerative colitisUlcerative colitis

EnteritisEnteritis

HemochromatosisHemochromatosis

Hemolytic anemia*Hemolytic anemia*

ContraindicationsContraindications

Manual of Neonatal Care, 6Manual of Neonatal Care, 6 thth Ed, 2008, Cloherty, Eichenwald, Stark Ed, 2008, Cloherty, Eichenwald, Stark

Signs of toxicity with ingestions of 10-20 mg/kg of Signs of toxicity with ingestions of 10-20 mg/kg of elemental iron. Serious toxicity is likely with ingestions of elemental iron. Serious toxicity is likely with ingestions of 60 mg/kg 60 mg/kg. Death has been reported after ingestion of as . Death has been reported after ingestion of as little as 650 mg little as 650 mg Carbonyl iron and IPCCarbonyl iron and IPC are nonionic: less toxicity than are nonionic: less toxicity than ferrous saltsferrous saltsGastric lavageGastric lavage with 1% to 5% sodium bicarbonate or with 1% to 5% sodium bicarbonate or sodium phosphate solution prevents absorption of iron: sodium phosphate solution prevents absorption of iron: limited valuelimited valueWhole bowel irrigationWhole bowel irrigation has been used to speed the has been used to speed the passage of undissolved iron tablets through the GI tract. passage of undissolved iron tablets through the GI tract. A polyethylene glycol electrolyte solutionA polyethylene glycol electrolyte solutionActivated Activated charcoal is uselesscharcoal is useless!!DeferoxaminDeferoxamine is the antidotee is the antidote

PoisoningPoisoning

The Harriet Lane Handbook, 18th EditionThe Harriet Lane Handbook, 18th Edition

The therapeutic dose should be calculated in The therapeutic dose should be calculated in terms of elemental ironterms of elemental iron11

Severe Iron Deficiency AnemiaSevere Iron Deficiency Anemia

4-6 mg/kg PO divided TID (up to 6o mg QID)4-6 mg/kg PO divided TID (up to 6o mg QID)

Mild to Moderate Iron Deficiency AnemiaMild to Moderate Iron Deficiency Anemia

3 mg/kg PO qDay or divided BID3 mg/kg PO qDay or divided BID

ProphylaxisProphylaxis

1-2 mg/kg PO; maximum 15 mg/day (up to 60-100 mg/d in 1-2 mg/kg PO; maximum 15 mg/day (up to 60-100 mg/d in adolescent)adolescent)

Oral Iron: DosesOral Iron: Doses


IAP: Treatment of IDAIAP: Treatment of IDA

The currently recommended dosage for infants & The currently recommended dosage for infants & children is children is 3 mg/kg/d3 mg/kg/d, higher doses are unnecessary, , higher doses are unnecessary, may increase side effects & reduce the patient may increase side effects & reduce the patient compliance.compliance.

AdolescentsAdolescents require require 60 mg60 mg of elemental iron in case of of elemental iron in case of mild anemia, and mild anemia, and 120 mg/d120 mg/d (60 (602) for moderate & severe 2) for moderate & severe anemia. Therapy should continue for eight weeks after anemia. Therapy should continue for eight weeks after the blood values have returned to normal.the blood values have returned to normal.

Recent studies have documented the efficiency of Recent studies have documented the efficiency of weekly / twice weeklyweekly / twice weekly oral iron supplementation. oral iron supplementation.


IAP Textbook of Pediatrics, 3IAP Textbook of Pediatrics, 3rdrd Ed, 2006 Ed, 2006

Indian Pediatrics 2008; 45:705-706Indian Pediatrics 2008; 45:705-706

Conventionally, the dose recommended is 4-6 Conventionally, the dose recommended is 4-6 mg/kg/day of elemental iron. However, smaller mg/kg/day of elemental iron. However, smaller doses have been found to be equally effective & doses have been found to be equally effective & better tolerated. Hence a dose of better tolerated. Hence a dose of 3 mg/kg/ day3 mg/kg/ day is is currently recommended currently recommended Absorptive capacityAbsorptive capacity of iron in duodenum is of iron in duodenum is saturated by 25 mg of elemental iron, hence higher saturated by 25 mg of elemental iron, hence higher doses will not increase the absorptiondoses will not increase the absorptionApproximately Approximately 2 months2 months treatment is required for treatment is required for Hb to come to normal level. Hb to come to normal level. Two more monthsTwo more months therapy is required to replenish the storestherapy is required to replenish the stores


Goodman & Gilman's The Pharmacological Basis of Therapeutics - 12th EditionGoodman & Gilman's The Pharmacological Basis of Therapeutics - 12th Edition

Children weighing 15–30 kg can take half the average Children weighing 15–30 kg can take half the average adult dose, while small children & infants can tolerate adult dose, while small children & infants can tolerate relatively large doses of iron (e.g., 5 mg/kg). The dose relatively large doses of iron (e.g., 5 mg/kg). The dose used is a compromise between the desired therapeutic used is a compromise between the desired therapeutic action and the adverse effects.action and the adverse effects.It is It is alwaysalways preferable to administer iron in the preferable to administer iron in the fasting fasting statestate, even if the dose must be reduced because of GI , even if the dose must be reduced because of GI side effects.side effects.Sustained high rates of red cell production require an Sustained high rates of red cell production require an uninterrupted supply of iron, and oral doses should be uninterrupted supply of iron, and oral doses should be spaced equallyspaced equally to maintain a continuous high to maintain a continuous high concentration of iron in plasma.concentration of iron in plasma.


Goodman & Gilman's The Pharmacological Basis of Therapeutics - 12th EditionGoodman & Gilman's The Pharmacological Basis of Therapeutics - 12th Edition

Duration of treatment is governedDuration of treatment is governed by the rate of recovery by the rate of recovery of Hb & the desire to create iron stores. The former depends of Hb & the desire to create iron stores. The former depends on the severity of the anemia. With a daily rate of repair of on the severity of the anemia. With a daily rate of repair of 0.2 g of Hb/dL of whole blood, the red cell mass usually is 0.2 g of Hb/dL of whole blood, the red cell mass usually is reconstituted within 1–2 months. Thus, an individual with reconstituted within 1–2 months. Thus, an individual with an Hb of 5 g/dL may achieve a normal complement of 15 an Hb of 5 g/dL may achieve a normal complement of 15 g/dL in about 50 days, whereas an individual with an Hb of g/dL in about 50 days, whereas an individual with an Hb of 10 g/dL may take only half that time. 10 g/dL may take only half that time. Much of the strategy of continued therapy depends on the Much of the strategy of continued therapy depends on the estimated future iron balance. Patients with an inadequate estimated future iron balance. Patients with an inadequate diet may require continued therapy with low doses of iron. If diet may require continued therapy with low doses of iron. If the bleeding has stopped, no further therapy is required the bleeding has stopped, no further therapy is required after the Hb has returned to normal. With continued after the Hb has returned to normal. With continued bleeding, long-term therapy clearly is indicated.bleeding, long-term therapy clearly is indicated.


NUTRITIONAL SUPPLEMENTATION IN LBW INFANTSNUTRITIONAL SUPPLEMENTATION IN LBW INFANTS

Iron supplementation is mandatory Iron supplementation is mandatory for all LBWfor all LBW infants infants

Given as 2 mg/kg/d (Max 15 mg/d) Given as 2 mg/kg/d (Max 15 mg/d)

Started when active erythropoiesis starts i.e. about Started when active erythropoiesis starts i.e. about 4 4 weeksweeks of postnatal age (AAP: formerly 2 months) of postnatal age (AAP: formerly 2 months)

EPO therapy: Start iron at 2 mg/kg/d as soon as EPO therapy: Start iron at 2 mg/kg/d as soon as tolerated & increase to 4 mg/kg/d (tolerated & increase to 4 mg/kg/d (6 mg/kg/d Optimum6 mg/kg/d Optimum) ) when feeds reach 100 mL/kg; when at full feeds, begin when feeds reach 100 mL/kg; when at full feeds, begin preterm vitamins; if not on iron after 2 wk of rh-EPO preterm vitamins; if not on iron after 2 wk of rh-EPO treatment consider: i.v. iron: treatment consider: i.v. iron: as high as 15 mg/kg/das high as 15 mg/kg/d have have been used to supplement neonate on EPO in the Tx of been used to supplement neonate on EPO in the Tx of anemia of Prematurityanemia of Prematurity


Feeding of Low Birth weight Infants, AIIMS- NICU protocols 2008, newbornwhocc.orgFeeding of Low Birth weight Infants, AIIMS- NICU protocols 2008, newbornwhocc.org

NUTRITIONAL SUPPLEMENTATION IN LBW INFANTSNUTRITIONAL SUPPLEMENTATION IN LBW INFANTS

Preterm infants need supplemental iron Preterm infants need supplemental iron after 2 weeksafter 2 weeks of age. The enteral nutrition appears the safest. Iron can of age. The enteral nutrition appears the safest. Iron can be supplied by preterm formula, HMF or medicinal drops. be supplied by preterm formula, HMF or medicinal drops.


Textbook of Pediatric Gastroenterology & Nutrition, Stefans Guandalin, 1Textbook of Pediatric Gastroenterology & Nutrition, Stefans Guandalin, 1 stst ed, 2004 ed, 2004

NUTRITIONAL SUPPLEMENTATION IN TERM INFANTSNUTRITIONAL SUPPLEMENTATION IN TERM INFANTS

Term infants should be sent home from the hospital on Term infants should be sent home from the hospital on iron-fortified formula (2 mg/kg/d)iron-fortified formula (2 mg/kg/d) if they are not if they are not breastfeedingbreastfeeding

To minimize the risk of iron deficiency anemia, all To minimize the risk of iron deficiency anemia, all formula-fed term infants should receive iron fortified formula-fed term infants should receive iron fortified formulas. Breastfed term infants should receive formulas. Breastfed term infants should receive supplemental iron beginning when they are aged several supplemental iron beginning when they are aged several months. months.

Elemental iron supplementation Elemental iron supplementation 1 mg/kg/d should be 1 mg/kg/d should be provided to infants who are exclusively fed breast milk provided to infants who are exclusively fed breast milk beyond 6 monthsbeyond 6 months of age. (or Iron supplemented formula: of age. (or Iron supplemented formula: 12 mg/Litre): Rudolph’s Peds, 2112 mg/Litre): Rudolph’s Peds, 21stst Ed, 2002 Ed, 2002



AAP Recommendation for Infants:AAP Recommendation for Infants:Breastfed infants should be supplemented with 1 mg/kg Breastfed infants should be supplemented with 1 mg/kg per day of oral iron beginning at 6 months until iron-rich per day of oral iron beginning at 6 months until iron-rich complementary foods (such as iron-fortified cereals) are complementary foods (such as iron-fortified cereals) are introduced.introduced.Formula-fed infants will receive adequate iron from Formula-fed infants will receive adequate iron from formula and complementary foods. Whole milk should formula and complementary foods. Whole milk should not be used before 12 months. (If used, risk of IDA, 1 not be used before 12 months. (If used, risk of IDA, 1 mg/kg/d recommended)mg/kg/d recommended)Infants ages 6 to 12 months need 11 mg of iron a day. Infants ages 6 to 12 months need 11 mg of iron a day. When infants are given complementary foods, red meat When infants are given complementary foods, red meat and vegetables with high iron content should be and vegetables with high iron content should be introduced early. Liquid iron supplements can beintroduced early. Liquid iron supplements can beused used if iron needs are not metif iron needs are not met by formula and by formula and complementary foods.complementary foods.


http://www.aap.org/pressroom/Ironfinal.pdf, October 2010

Choice of Milk for FeedingChoice of Milk for Feeding

Ref. : Deptt. of Agriculture, United States

• Top Milk :Term Term

Breast MilkBreast MilkCow’s Cow’s MilkMilk

Buffalo’s Buffalo’s MilkMilk

Goat’s Goat’s MilkMilk

Calories (Kcal/dl)Calories (Kcal/dl) 6767 6767 117117 7272

Protein (gm/dl)Protein (gm/dl) 1.11.1 3.23.2 4.34.3 3.33.3

Fat (gm/dl)Fat (gm/dl) 4.54.5 4.14.1 6.56.5 4.54.5

Carbohydrate (gm/dl)Carbohydrate (gm/dl) 7.17.1 4.44.4 5.15.1 4.44.4

Calcium (mg/dl)Calcium (mg/dl) 3333 120120 169169 134134

Phosphorus (mg/dl)Phosphorus (mg/dl) 1515 9090 117117 111111

Iron (mg/dl)Iron (mg/dl) 0.030.03 0.20.2 0.120.12 0.050.05

Vitamin A (IU/dl)Vitamin A (IU/dl) 250250 70-22070-220 178178 185185

Sodium (mEq/dl)Sodium (mEq/dl) 0.80.8 0.760.76 0.520.52 0.500.50

Folic Acid (mcg/dl)Folic Acid (mcg/dl) 55 55 66 11

Composition of various feedsComposition of various feeds

Mineral & Mineral & Vitamin per Vitamin per 100 Kcal100 Kcal

Preterm-Preterm-RNI RNI (AAPCON (AAPCON 1998)1998)

Preterm-Preterm-EBM (per EBM (per 100 ml)100 ml)

Preterm Preterm EBM + HMF EBM + HMF (Per 100 ml)(Per 100 ml)

Preterm Preterm Formula (Per Formula (Per 100 ml)100 ml)

Calories Calories (Kcal/kg/d)(Kcal/kg/d)

105-130105-130 6767 8181 8080

Protein Protein (gm/kg/d)(gm/kg/d)

3.5-43.5-4 1.61.6 22 22

Carbohydrate Carbohydrate (gm/kg/day)(gm/kg/day)

11-15.511-15.5 7.37.3 9.79.7 9.19.1

Calcium Calcium (mg)(mg)

175175 2525 125125 128128

Phosphorus Phosphorus (mg)(mg)

9191 1414 6464 6464

Iron (mg)Iron (mg) 1.7-2.51.7-2.5 0.090.09 0.090.09 0.80.8

Although iron stores are low in preterm & term-SFDs, requirements are minimum in first few weeks of life!

Journal of Neonatology, NNF-India, Vol. 18, No.1, Jan-Mar 2004

Birth weight 1000 gm Birth weight >1000 gm

Iron @ 3-4 mg/kg/d Iron @ 2-3 mg/kg/d

Start at 4-6 weeks of life when active erythropoiesis starts Start earlier at 4 weeks of life if baby had frequent phlebotomies:

even if baby on LBW formula/HMF Continue iron for atleast 1 year, and if weaning is not adequate

continue till 2-3 years of age!

Iron Supplementation in LBWIron Supplementation in LBW

Therapeutic Iron TrialTherapeutic Iron TrialA therapeutic iron trial is a trial of oral iron therapy A therapeutic iron trial is a trial of oral iron therapy without additional laboratory testingwithout additional laboratory testing in a patient in a patient with a microcytic anemia with a microcytic anemia andand a history of dietary a history of dietary deficiency or known history of blood loss. An deficiency or known history of blood loss. An increase in the hemoglobin concentration of increase in the hemoglobin concentration of 1 g/dL 1 g/dL or greater after 2 to 4 weeksor greater after 2 to 4 weeks of therapy confirms of therapy confirms the diagnosis of iron deficiency. If the hemoglobin the diagnosis of iron deficiency. If the hemoglobin level does not increase, additional laboratory level does not increase, additional laboratory testing is necessary and other diagnoses should testing is necessary and other diagnoses should be considered!be considered!


5-Minute Pediatric Consult, 4th Edition, 2005

AdministrationAdministration

Best taken on an Best taken on an empty stomachempty stomach 1 hour before 1 hour before or 2 hours after mealsor 2 hours after meals

Take with a full glass of water (8 ounces or 240 Take with a full glass of water (8 ounces or 240 milliliters)milliliters)

Avoid taking antacids, dairy products, tea, or Avoid taking antacids, dairy products, tea, or coffee within coffee within 2 hours before or after2 hours before or after this this medication because they will decrease its medication because they will decrease its effectiveness.effectiveness.

Oral Iron TherapyOral Iron Therapy

AdministrationAdministrationTo maximize the response to iron in an adult patient To maximize the response to iron in an adult patient with moderate to severe IDA, a standard iron preparation with moderate to severe IDA, a standard iron preparation should be given three to four times a day between meals.should be given three to four times a day between meals.A A fourth dose of iron at bedtimefourth dose of iron at bedtime will help maintain iron will help maintain iron delivery to the marrow during late evening & night hours. delivery to the marrow during late evening & night hours. Otherwise, the serum iron can decline to iron-deficient Otherwise, the serum iron can decline to iron-deficient levels during the night, thereby dampening the levels during the night, thereby dampening the marrow's marrow's proliferative responseproliferative response. . Patients who are achlorhydric or who have had gastric Patients who are achlorhydric or who have had gastric surgery should be treated with iron elixir, because the surgery should be treated with iron elixir, because the removal of the tablet coat depends on normal stomach removal of the tablet coat depends on normal stomach acidity.acidity.



National Nutritional Anemia Control National Nutritional Anemia Control Program (NNACP)Program (NNACP)

Available data indicates that ferrous iron is Available data indicates that ferrous iron is

absorbed 4-10 times better than ferric ironabsorbed 4-10 times better than ferric ironThe daily dosage of Iron Folic Acid (IFA) The daily dosage of Iron Folic Acid (IFA)

supplement (supplement (20mg elemental iron + 100 mcg folic 20mg elemental iron + 100 mcg folic

acidacid) recommended for children 6-35 months for ) recommended for children 6-35 months for

prophylaxisprophylaxisIFA supplementation should be done daily for IFA supplementation should be done daily for

minimum of 100 daysminimum of 100 days in the first year of life and in the first year of life and

for minimum of 100 days in the second year of for minimum of 100 days in the second year of

lifelife

Iron may reduce the frequency and severity of breath-Iron may reduce the frequency and severity of breath-holding attacks (or spells) in children but more research holding attacks (or spells) in children but more research is needed to determine the is needed to determine the extentextent of this effect. of this effect.

Spontaneously resolve by the time the child reaches Spontaneously resolve by the time the child reaches seven years of age. seven years of age.

The review of controlled clinical trials found that iron The review of controlled clinical trials found that iron supplementation may reduce the frequency and severity supplementation may reduce the frequency and severity of breath-holding attacks, particularly if the child is of breath-holding attacks, particularly if the child is anemic. It is not known if this benefit is anemic. It is not known if this benefit is sustained after sustained after three months orthree months or if iron therapy should be continued until if iron therapy should be continued until the child grows out of the breath-holding episodes.the child grows out of the breath-holding episodes.

Dose of 6 mg/kg/d Dose of 6 mg/kg/d 4 months (IAP Chennai, 2004) 4 months (IAP Chennai, 2004)

Breath-holding Spells & IronBreath-holding Spells & Iron

Malnutrition & Iron TherapyMalnutrition & Iron Therapy

Severely malnourished patients have a reduced iron-Severely malnourished patients have a reduced iron-binding capacity, they are neither able to withhold iron binding capacity, they are neither able to withhold iron from invading organisms nor to prevent the toxic effects from invading organisms nor to prevent the toxic effects of iron itself. of iron itself. During the acute & intermediate phasesDuring the acute & intermediate phases of of Tx iron should Tx iron should not be givennot be given, even in the presence of , even in the presence of severe anemia. In the rehabilitation phase an iron severe anemia. In the rehabilitation phase an iron supplement should be given.supplement should be given.

Children with kwashiorkor or marasmus should be Children with kwashiorkor or marasmus should be assumed to be severely anemic. However, oral iron assumed to be severely anemic. However, oral iron supplementation should be supplementation should be delayed untildelayed until the child the child regains appetite and starts gaining weight, usually after regains appetite and starts gaining weight, usually after 14 days14 days

Textbook of Pediatric Gastroenterology & Nutrition, Stefans Guandalin, 1Textbook of Pediatric Gastroenterology & Nutrition, Stefans Guandalin, 1 stst ed, 2004 ed, 2004

MalnutritionMalnutrition

Deworming & IronDeworming & Iron

Where hookworms are Where hookworms are endemicendemic (prevalence 20-30% or (prevalence 20-30% or greater) it will be most effective to combine iron greater) it will be most effective to combine iron supplementation with antihelminthic treatment to adults supplementation with antihelminthic treatment to adults and children above the age of 2 years. Universal and children above the age of 2 years. Universal antihelminthic treatment, irrespective of infection status, antihelminthic treatment, irrespective of infection status, is recommended is recommended at least annuallyat least annually. High-risk groups, . High-risk groups, women and women and childrenchildren, should be treated more intensively , should be treated more intensively ((2-3 times per year2-3 times per year). The following single-dose ). The following single-dose treatments are recommended:treatments are recommended:

•Albendazole 400 mg single doseAlbendazole 400 mg single dose

•Mebendazole 500 mg single doseMebendazole 500 mg single dose

•Levamisole 2.5 mg/kg single doseLevamisole 2.5 mg/kg single dose

•Pyrantel 10 mg/kg single dosePyrantel 10 mg/kg single dose


Infection & Iron SupplementationInfection & Iron Supplementation

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

Indian Pediatrics 2008; 45:705-706, Indian Pediatrics 2008; 45:705-706, Nutrition in pediatrics 3rd ed, 2003Nutrition in pediatrics 3rd ed, 2003

Iron supplementation & Infection Iron supplementation & Infection riskrisk

Some studies have found that iron Some studies have found that iron supplementation can lead to an supplementation can lead to an increase in infectious disease morbidityincrease in infectious disease morbidity in areas where bacterial in areas where bacterial infections are common. For example, children receiving iron-enriched infections are common. For example, children receiving iron-enriched foods have demonstrated an increased rate in diarrhea overall and foods have demonstrated an increased rate in diarrhea overall and enteropathogen shedding. Iron enteropathogen shedding. Iron deficiency protects against infectiondeficiency protects against infection by by creating an unfavorable environment for bacterial growth. Nevertheless, creating an unfavorable environment for bacterial growth. Nevertheless, while iron deficiency might lessen infections by certain pathogenic while iron deficiency might lessen infections by certain pathogenic diseases, it also leads to a reduction in resistance to other strains of diseases, it also leads to a reduction in resistance to other strains of viral or bacterial infections, such as Salmonella typhimurium or viral or bacterial infections, such as Salmonella typhimurium or Entamoeba histolytica. Overall, it is sometimes difficult to decide Entamoeba histolytica. Overall, it is sometimes difficult to decide whether iron supplementation will be beneficial or harmful to an whether iron supplementation will be beneficial or harmful to an individual in an environment that is prone to many infectious diseases.individual in an environment that is prone to many infectious diseases.Iron deficiency is associated with increased susceptibility to infection. Iron deficiency is associated with increased susceptibility to infection. However, excessive iron intake appears to be linked to oxidative stress However, excessive iron intake appears to be linked to oxidative stress and to more infections as well. and to more infections as well. Iron may help in combating infection by Iron may help in combating infection by up-regulating IL-1up-regulating IL-1 production. Iron may predispose to infection by production. Iron may predispose to infection by nourishing certain species of bacteria or by inhibiting the induction of nourishing certain species of bacteria or by inhibiting the induction of nitric oxide synthase!nitric oxide synthase!

5-Minute Pediatric Consult, 4th Edition, 20055-Minute Pediatric Consult, 4th Edition, 2005

Iron supplementation & InfectionIron supplementation & Infection

How does infection affect the diagnosis of How does infection affect the diagnosis of anemia?anemia?Common childhood infections can be associated with a Common childhood infections can be associated with a mild microcytic anemia. Acute infection also affects some mild microcytic anemia. Acute infection also affects some of the laboratory tests used to diagnose the cause of of the laboratory tests used to diagnose the cause of microcytic anemia. With infection there is a shift of iron microcytic anemia. With infection there is a shift of iron from serum to storage sites. Serum iron is reduced and from serum to storage sites. Serum iron is reduced and ferritin increases. It is, therefore, preferable to evaluate a ferritin increases. It is, therefore, preferable to evaluate a microcytic anemia 3 to 4 weeks after an infection microcytic anemia 3 to 4 weeks after an infection resolves!resolves!

Nutrition Reseach, Volume 27, Issue 5, Pages 279-282 (May 2007)Nutrition Reseach, Volume 27, Issue 5, Pages 279-282 (May 2007)

Important Points in TherapyImportant Points in Therapy

Folic acidFolic acid should be should be addedadded to the iron to the iron supplements to prevent folic acid deficiency supplements to prevent folic acid deficiency anemiaanemiaMore scientific data is required on the More scientific data is required on the magnitude of vitamin B12 and zinc deficiencies magnitude of vitamin B12 and zinc deficiencies and the benefits of adding these micronutrients and the benefits of adding these micronutrients before their routine supplementation in before their routine supplementation in conjunction with iron can be considered as conjunction with iron can be considered as public health intervention measure under NNACPpublic health intervention measure under NNACPZinc has an inhibitory effect on iron absorption. Zinc has an inhibitory effect on iron absorption. However, this inhibitory effect lasts less than 30 However, this inhibitory effect lasts less than 30 minutesminutes11

Blood: principles and practice of hematology, Volume 1, By Robert I. Handin, Samuel E. Lux, Thomas P. StosselBlood: principles and practice of hematology, Volume 1, By Robert I. Handin, Samuel E. Lux, Thomas P. Stossel

Strategies to minimize GI side effectsStrategies to minimize GI side effects

Start at a Start at a lower doselower dose and increase gradually and increase gradually over 4 to 5 daysover 4 to 5 days

Giving Giving divided dosesdivided doses or the lowest effective or the lowest effective dosedose

Taking supplements Taking supplements with mealswith meals

Single daily dose at Single daily dose at bedtimebedtime1 1 (empty stomach)(empty stomach)

Intolerance despite all measures, consider Intolerance despite all measures, consider changing thechanging the preparation preparation


Strategies to minimize GI side effectsStrategies to minimize GI side effects

Problems with Problems with constipationconstipation can be minimized can be minimized by increasing water and fiber intakeby increasing water and fiber intake

Aside from the unpleasant taste, intolerance to Aside from the unpleasant taste, intolerance to oral iron is uncommon in young children, oral iron is uncommon in young children, although older children and adolescents although older children and adolescents sometimes have gastrointestinal complaints. sometimes have gastrointestinal complaints.

Natural Way?:Natural Way?: Pomegranate juice 0.2 Pomegranate juice 0.2 g/cup, g/cup, digestible iron. (0.3-1.2 mg/100 gm)digestible iron. (0.3-1.2 mg/100 gm)



Compliance in the first monthCompliance in the first month of therapy is of therapy is important as majority of iron absorption occurs important as majority of iron absorption occurs during this period. It is continued for at least 2-3 during this period. It is continued for at least 2-3 months after hemoglobin becomes normal, to months after hemoglobin becomes normal, to replenish storesreplenish storesIron supplementation may increase hemolysis if Iron supplementation may increase hemolysis if adequate vitamin E therapy is not supplied: adequate vitamin E therapy is not supplied: Avoid use in premature infants until the Avoid use in premature infants until the vitamin vitamin E storesE stores, deficient at birth are , deficient at birth are replenishedreplenished11




With treatment, one must address the cause of With treatment, one must address the cause of

IDAIDAControl of infections: Iron deficiency anemia Control of infections: Iron deficiency anemia

and infections are inter-linked. Recurrent and infections are inter-linked. Recurrent

infections can lead to anemia of chronic infections can lead to anemia of chronic

infections adding to the burden of iron deficiency infections adding to the burden of iron deficiency

anemia. Hence, infections should be treated anemia. Hence, infections should be treated

energetically.energetically.Steps to prevent further occurrence of IDASteps to prevent further occurrence of IDA


While adequate iron medication is given, the family While adequate iron medication is given, the family must be educated about the patient's diet, and the milk must be educated about the patient's diet, and the milk consumption should be limited to a reasonable quantity, consumption should be limited to a reasonable quantity, preferably 500 mLpreferably 500 mL (1 pint)/24 hr or less. This reduction (1 pint)/24 hr or less. This reduction has a dual effect: The amount of iron-rich foods is has a dual effect: The amount of iron-rich foods is increased. increased. Excess intake of cow's milk leads to deficiency. Milk is a Excess intake of cow's milk leads to deficiency. Milk is a poor source of iron and very little iron present in cow's poor source of iron and very little iron present in cow's milk is not bioavailable. Cow's milk also produces blood milk is not bioavailable. Cow's milk also produces blood loss & loss & milk protein sensitive enteropathymilk protein sensitive enteropathy (occult blood (occult blood loss) in some. Iron present in breast milk is loss) in some. Iron present in breast milk is more more bioavailablebioavailable (49% Vs 10%) & is absorbed sue to the (49% Vs 10%) & is absorbed sue to the presence of lactoferrin. presence of lactoferrin.

Nutrition in Pediatrics 3rd ed, 2003Nutrition in Pediatrics 3rd ed, 2003


Since the Since the calcium, phosphorouscalcium, phosphorous and and magnesiummagnesium contained in multivitamins can impair iron absorption, the contained in multivitamins can impair iron absorption, the iron contentiron content of these supplements of these supplements should not be includedshould not be included in the therapeutic iron dose. For the same reason, the in the therapeutic iron dose. For the same reason, the iron iron supplements & multivitamin should be taken supplements & multivitamin should be taken at at separateseparate timestimesReplacement therapy may begin as soon as iron deficiency Replacement therapy may begin as soon as iron deficiency is detected; however, it is essential to determine and is detected; however, it is essential to determine and correct the underlying causecorrect the underlying causeOnce anemia has corrected and iron stores have Once anemia has corrected and iron stores have normalized; a normalized; a low maintenancelow maintenance dose may be prescribed if dose may be prescribed if an ongoing need for additional iron (e.g. menorrhagia, an ongoing need for additional iron (e.g. menorrhagia, growth spurt). Dietary modification may also be considered. growth spurt). Dietary modification may also be considered. Consider similar supplementation for iron depleted but not Consider similar supplementation for iron depleted but not anemic patientsanemic patients



Some Common PreparationsSome Common Preparations

Syr. BrandSyr. Brand SaltSalt Elemental Elemental Iron/ 5 mLIron/ 5 mL

Folate Folate (mg) (mg)

B12 B12 ((g)g)

Misc.Misc.

VitcofolVitcofol FumarateFumarate 32.832.8 0.50.5 55

HemsiHemsi FumarateFumarate 3030 0.50.5 55 Lysine, Cu, Lysine, Cu, Zn, MnZn, Mn

FortironFortiron

VegeferVegeferSod. Sod. Feredetate Feredetate (Ferric)(Ferric)

3333 --

Haem UpHaem Up Ferric Amm Ferric Amm CitrateCitrate

2626 0.50.5 --

Dexorange Dexorange PedPed

Ferric Amm Ferric Amm CitrateCitrate

10.2510.25 0.20.2 2.52.5

Tonoferon Tonoferon PediatricPediatric

Colloidal Colloidal ironiron

80 80 (250 mg (250 mg in Adult in Adult Prep)Prep)

0.20.2 22

HepatoglobHepatoglobine Mikrosine Mikros

Peptonized Peptonized ironiron

3030 0.20.2 2.52.5 17% 17% elemental elemental ironiron




B12 B12 ((g)g)

Misc.Misc.

Faa 20 Faa 20 (Lupin)(Lupin)

Amino Acid Amino Acid ChelateChelate

1515 0.50.5 --

Globiron Globiron (Aglowmed)(Aglowmed)

Ferium Ferium ((Emcure)Emcure)

IPCIPC 5050 -- --

Hemfer Hemfer (Alkem)(Alkem) Fe Glycine Fe Glycine SO4SO4

16.716.7 0.170.17 2.52.5 Zn, BiotinZn, Biotin


Syr. BrandSyr. Brand SaltSalt ElementaElemental Iron/ 5 l Iron/ 5 mLmL


B12 B12 ((g)g)

Misc.Misc.

Ferium-XT Ferium-XT

Feronia-XTFeronia-XT

Ferrochelate-XTFerrochelate-XTFerikind, Ferikind, VitcoferVitcofer

AscorbateAscorbate 3030 0.50.5 --

Orofer-XTOrofer-XT

IrozorbIrozorbAscorbateAscorbate 3030 0.550.55 --

Irentia Irentia (Akumentis)(Akumentis)

AscorbateAscorbate 3030 0.50.5 500 500 g g MethylcobalaminMethylcobalamin

LivogenLivogen GluconateGluconate 1515 0.250.25

JP ToneJP Tone GluconateGluconate 11.711.7 0.380.38 55 B6, Zn, B6, Zn, NiacinNiacin

R.B. ToneR.B. Tone GluconateGluconate 1515 0.250.25 1.251.25 Cal Cal LactateLactate




B12 B12 ((g)g)

Misc.Misc.

ImferonImferon CarbonylCarbonyl 2525 0.50.5 66 eZn 11 mgeZn 11 mg

HemferHemfer Ferrous Ferrous glycine SO4glycine SO4

16.716.7 0.170.17 2.52.5 Zn, BiotinZn, Biotin

KidicareKidicare Ferrous Ferrous gluconategluconate

55 Zn, Mg, E, Zn, Mg, E, Lysine, B1, Lysine, B1, B2, B6, B12B2, B6, B12

Nutrifacts FeNutrifacts Fe Ferrous Ferrous GluconateGluconate

3333 0.050.05 1.51.5 CuSO4, Vit C CuSO4, Vit C & A, Mo& A, Mo

ParnikaParnika Ferric Amm Ferric Amm CitrateCitrate

13.313.3 0.170.17 2.52.5 Zn, B6Zn, B6

Nicofer Nicofer (Piramal)(Piramal)

Ferric Amm Ferric Amm CitrateCitrate

8.88.8 0.150.15 2.52.5

RichProRichPro Choline Choline CitrateCitrate

11 Least IrritantLeast Irritant Zn, Mg, B1, Zn, Mg, B1, B2, B6, B12B2, B6, B12

Zest, CHERIZest, CHERI SeveralSeveral


DROPS BrandDROPS Brand SaltSalt Elemental Elemental Iron/ 1 mLIron/ 1 mL


B12 B12 ((g)g)

Misc.Misc.

TonoferonTonoferon ColloidalColloidal 2525 0.20.2 55

HepatoglobineHepatoglobine PeptonizedPeptonized 2020 0.20.2 44

Ferrochelate XTFerrochelate XT AscorbateAscorbate 1010 0.20.2 44 Lysine Lysine 150 mg150 mg

Feronia-XTFeronia-XT

IrentiaIrentiaAscorbateAscorbate 1010 0.10.1 --

Orofer-XTOrofer-XT

HemsiHemsiAscorbateAscorbate 1010 --

VegeferVegefer Sod. Sod. FeredetateFeredetate

88 -- --

Vitcofol drops donot contain Iron & have only vit B12 & Folic acid. In Vitcofol drops donot contain Iron & have only vit B12 & Folic acid. In contrast vitcofol injection contains only vitamin B12.contrast vitcofol injection contains only vitamin B12.


Tab. BrandTab. Brand SaltSalt Elemental Elemental Iron/ tabIron/ tab


B12 B12 ((g)g)

Misc.Misc.

Livogen XTLivogen XT AscorbateAscorbate 100100 1.51.5 -- eZn 22.5 eZn 22.5 mgmg

Feronia XTFeronia XT

Ferium XTFerium XT

IrozorbIrozorb

AscorbateAscorbate 100100 1.51.5 -- --

Orofer XTOrofer XT AscorbateAscorbate 100100 1.11.1 --

Cap. VitcofolCap. Vitcofol FumarateFumarate 100100 0.750.75 7.57.5 eZn 7.5 eZn 7.5 mg, B6mg, B6

Tab. AlohaTab. Aloha

HbFast ZHbFast Z

Cap. ImferonCap. Imferon

CarbonylCarbonyl 100100 1.51.5 1515 Zn, Vit. CZn, Vit. C

Tab. Ferronine Tab. Ferronine (gsk)(gsk)

Ferrous bis Ferrous bis glycinateglycinate

6060 11 55 eZn 15 mgeZn 15 mg

In terms of efficacy all available iron In terms of efficacy all available iron preparations are effective though timing preparations are effective though timing of response may varyof response may vary

Iron supplements should be prescribed Iron supplements should be prescribed in right form, dose & durationin right form, dose & duration

Cause of IDA should be addressed Cause of IDA should be addressed whenever possiblewhenever possible

SummarySummary

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Oral_iron

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