Oral Iron Supplementation: Review

Dr. KISHORE CHANDKI Kids Care Clinic, Indore (M.P.) INDIA

Oral Iron Therapy in Children

Cost effective Safe Convenient Well tolerated Corrects anemia just as rapidly & completely as parenteral iron in most cases Preferred to intravenous therapy Ideal mode of treatment for IDA

IAP Textbook of Pediatrics, 3rd Ed, 2006, Basic & Clinical Pharmacology, Katzung, 10th Ed

Principles of Treatment

Use oral iron

Establish & treat the cause Replace iron deficit in total

Iron Preparations Inorganic

Ferrous sulphate Ferrous fumarate Ferric ammonium citrate

Organic
Ferric Polymaltose

Chelated Iron
Ferrous bis glycinate

Technological
Ferrous Ascorbate

Element
Carbonyl Iron

Iron Absorption
Primarily duodenum (& proximal jejunum) Hem iron 20-40%, AA directly without carrier, o with HCl 20Non hem (plant) 10% Increased in IDA to 30% Mechanisms of absorption:
By active absorption (DMT1) mucosal & ferroportin1 (basal)
Anemia & hypoxemia & Erythropoiesis, hereditary hemochromatosis, iron stores but less affected with plasma iron & Inflammation & malignancy What is the elation between Hepcidin & ferroportin? Anemia of CD Enters mucosal cells as Ferrous either A. Ferric Apoferritin ferritin (Mucosal block) = Ferritin curtain B. Transported to serum as ferrous What are the factors that govern these processes? About 1 mg is absorbed daily

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

Iron Absorption Parameters

Stability in gastric acids Form administered Status of patients iron stores Dose oElemental iron oBioavailability oPhytate inhibition

Iron Absorption Parameters

Elemental iron Amount of iron in a supplement that is available for absorption Bioavailability Fraction of the elemental iron that reaches the systemic circulation Phytate inhibition Reducing the absorption of iron by 1515-fold

Elemental Content Vs Bioavailability

Ferrous sulphate Ferrous bis glycinate Ferrous succinate IPC Ferrous fumarate Ferrous glycine sulphate Ferrous ascorbate Ferrous pyrophosphate Ferric ammonium citrate Ferrous gluconate Carbonyl Iron Sod. Feredetate (Ferric) Colloidal Iron 20% 20 35 34 33 23 14 25 18 12 >90 14 50 100% Standard ?199 123 ?~FS 101 101 97 89 74 89 70 ? ?

Status of Iron Stores

In persons with normal stores 10% of an oral dose is absorbed, this is increased to 20%-30% in persons with 20%inadequate iron stores Peak reticulocyte count experienced on days 510 after 5 initiation of iron therapy. Following this, Hb rises on average by 0.250.4 g/dL/day or hematocrit rises 1%/day 0.25 during first 710 days. Thereafter, Hb rises more slowly: 7 Thereafter, slowly: 0.1 0.10.15 g/dL/day. As the hemoglobin level rises, iron absorption declines and the rate of RBC production (which was up to 3 times the normal) falls, regardless of the oral iron intake. intake. Therefore, the dosage can be reduced as the hemoglobin rises to level above 11 to 12 gm%. This will help guarantee patient compliance for a therapy that must continue for several months.
Harrison's Principles of Internal Medicine, 14th Ed.,1998, Vol. 1, Pg 642

Review of Preparations: Ferrous Salts

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

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

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

Iron Amino-acid Chelates AminoConjugates of the ferrous or ferric ion with amino-acids aminoFerrous bis-glycinate (20% elemental iron), ferric bistrisglycinate and ferrous glycine sulphate (FGS) FBG: Two molecules of the amino acid glycine are bound covalently to a molecule of iron. They have no effect on the color or taste of food products Main advantage: relatively high bioavailability in the presence of dietary inhibitors. Chelates prevent iron from inhibitors. binding to inhibitors in food or precipitating as insoluble ferric hydroxide in the pH of the small intestine Rise of Hb with FGS Vs FS is equivalent Costlier
Advances in Pediatrics, Dutta, Anupam Sachdev, 1st Ed, 2007

Iron Polymaltose Complex (IPC)

Contains non-ionic iron and polymaltose in a stable noncomplex Bioavailability similar to FS Absorption not affected by food or milk To date there are no reports of any interactions with foods or medicines Does not stain teeth Better absorbed, lesser GI side effects Improvement in Hb level is less w.r.t. other preparations Intoxication rare: Iron of IPC is absorbed in the intestine rare: through a self-limiting competitive interchange of ligands, selfso that the intestinal transport system is saturated in case of over dosage
Advances in Pediatrics, Dutta, Anupam Sachdev, 1st Ed, 2007

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

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

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

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

IAP Textbook of Pediatrics, 3rd Ed, 2006

Ferrous Ascorbate
Synthetic molecule of ascorbic acid & iron Ascorbic acid enhances iron absorption Ascorbic acid reduces ferric iron to ferrous iron which remains soluble even at neutral pH

Comparison of Salts
Salt Ferrous sulphate Ferrous Fumarate Amino Acid Chelates IPC Carbonyl Colloidal GI Side Teeth Food/Drug Poisoning Effects staining interaction Potential ~23% + +++ +++ + Less Less ?Less Less + ++ + + + Nil Nil ?

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

Harrisons Principles of Internal Medicine, 17th Edition.

Treatment of IDA
Some contain 'absorption enhancing' substances enhancing' such as amino acids & ascorbic acid. No evidence shows that addition of any trace metal, vitamin or other hematenic substance significantly increases the response to simple ferrous salts Others are advertised as delayed-released delayedformulations aimed at prolonging iron absorption over several hours. All these are expensive. Moreover, attempts to enhance absorption can increase the incidence of GI side effects.
Nelson Textbook of pediatrics, 18th Ed, 2008

Response to Iron Therapy

Time after Iron Administration 1212-24 hr 3636-48 hr 4848-72 hr 4-30 days 1-3 months Response Subjective improvement; improvement; decreased irritability, increased appetite Initial bone marrow response Reticulocytosis, peak at 5 -7 days Increase in hemoglobin level Repletion of stores
Nelson Textbook of pediatrics, 18th Ed, 2008

Response to Iron Therapy

Pica, pagophagia, amylophagia (laundry starch/ raw rice) and non-specific symptoms disappear nonwithin one week Of the epithelial lesions, those affecting tongue and nails are most responsive to treatment. After 1-2 weeks of therapy, small filiform papillae are seen on the tongue By 3 month, the tongue is usually normal Koilonychia usually disappears within 3-6 months A positive hematological response has been defined as rise of Hb 0.1 g/dL daily (up to 0.4 g)
J. K. Science Vol. 3 No.4. October-December 2001 October-

Suboptimal Response: Causes

Poor compliance (failure or irregular administration): major problem Discontinuation of Tx after initial 3 to 4 weeks because of feeling of well being & disappearance of symptoms of anemia Sub therapeutic dose (< 3-6 mg/kg/d) 3Poorly absorbed preparation, e.g. enteric coated tab? preparation, Iron administration soon after intake of milk (phosphates) or cereals (phytates) Persistent blood loss (occult or frank), with the patient losing iron as fast as it is replaced: milk allergy, polyps, ulcer disease, esophagitis, menorrhagia
The Short Textbook of Pediatrics, Suraj Gupte, 9th Ed,2001Pg 412

Suboptimal Response
Incorrect diagnosis of IDA in thalassemia, lead poisoning or anemia of chronic infection Coexistent disease that interferes with absorption or utilization of iron (e.g., infection, IBD, malignancy, hepatic or renal disease, or concomitant deficiencies of, for instance, vitamin B12, folic acid, thyroid, associated lead poisoning) Impaired GI absorption (e.g., Celiac disease, giardiasis, H. Pylori infection, autoimmune gastritis, concurrent administration of large amounts of antacids, which bind iron and H2RA)

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

Interaction
Iron absorption may be decreased by antacids or magnesium, calcium, supplements containing aluminum, magnesium, calcium, zinc, zinc, PPI, & H2 RA Iron may decrease the absorption of bisphosphonates, tetracyclines, tetracyclines, levodopa, methyldopa, levothyroxine and penicillamine. (Space administration apart by at least 2 hours) Absorption of quinolones may be qed due to formation of ferric-quinolone complex ferricResponse to iron therapy may be delayed in patients receiving chloramphenicol Concurrent administration of u200 mg vitamin C per 30 mg elemental iron oes the absorption
The Harriet Lane Handbook, 18th Edition

Interaction
Phytates in cereals & oxalates (vegetables), high (vegetables), phosphate in cow's milk (+casein) & excess of zinc also reduce absorption. Thus children who take only milk & rice tend to have iron deficiency Calcium salts (carbonates/oxalates) & eggs in the diet inhibit iron absorption Tannic acid present in tea & coffee, forms complexes coffee, with iron salts & inhibits absorption Lactose, ascorbic acid, fruit juices and certain amino acids such as cystine, lysine & histidine enhance iron absorption HCl of the gastric juice facilitates iron absorption from the ferric complexes, preventing its precipitation by phosphates & maintaining iron in ferrous form
Nutrition & Child Development, Dr. K E Elizabeth, 2nd Ed, 2002, Pg 103

Interaction
Acid medium & cobalt increase iron absorption. Consumption of lemon juice, fruit juice & curd with food will increase absorption due to presence of vitamin C. Heme iron from animal source (from myoglobin and red cells in red meats) is better absorbed. Ascorbic acid & meat facilitate the absorption of nonheme iron. Ascorbate forms complexes with &/or reduces ferric to ferrous iron. Meat facilitates the absorption of iron by stimulating production of gastric acid; other effects also may be involved. Iron supplementation reduce cough induced by ACE inhibitors. (Ref. Goodman & Gilman's The Pharmacological Basis of Therapeutics)

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

Side Effects
Gastrointestinal distress is the most prominent . Abdominal pain, nausea, vomiting, or constipation may lead to noncompliance. Although small doses of iron or iron preparations with delayed release may help somewhat, the gastrointestinal side effects are a major impediment to the effective treatment of a number of patients GI side effects are more common in adults and adolescents and are reported to occur in 15-20 % 15patients. To overcome this side effect various measures suggested include administration after meals and at bed time. Decreased intestinal motility during sleep may improve absorption
Harrisons Principles of Internal Medicine, 17th Edition.

Side Effects
Temporary staining of teeth & tongue with some preparations: Can be avoided by correctly placing the drops at the back of the tongue or drinking through straw. Or rinsing the mouth or brushing the teeth after taking the medicine. Black stools: The iron in the stools and supplement may stain clothing. Common, but may obscure the diagnosis of continued GI blood loss!

Rudolphs Pediatrics, 21st Ed, 2002, Pg 1528

Side Effects
Intolerance to oral preparations of iron primarily is a function of the amount of soluble iron in the upper GI tract & of psychological factors. A good policy is to initiate therapy at a small dosage, to demonstrate freedom from symptoms at that level, and then gradually to increase the dosage to that desired.

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

Contraindications
Hypersensitivity to iron salts or any component Peptic ulcer disease Ulcerative colitis Enteritis Hemochromatosis Hemolytic anemia*

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

Poisoning
Signs of toxicity with ingestions of 10-20 mg/kg of 10elemental iron. Serious toxicity is likely with ingestions of u 60 mg/kg. Death has been reported after ingestion of as mg/kg. little as 650 mg Carbonyl iron and IPC are nonionic: less toxicity than ferrous salts Gastric lavage with 1% to 5% sodium bicarbonate or sodium phosphate solution prevents absorption of iron: limited value Whole bowel irrigation has been used to speed the passage of undissolved iron tablets through the GI tract. A polyethylene glycol electrolyte solution Activated charcoal is useless! useless! Deferoxamine is the antidote Deferoxamine
The Harriet Lane Handbook, 18th Edition

Oral Iron: Doses

The therapeutic dose should be calculated in terms of elemental iron1
Severe Iron Deficiency Anemia 4-6 mg/kg PO divided TID (up to 6o mg QID) Mild to Moderate Iron Deficiency Anemia 3 mg/kg PO qDay or divided BID Prophylaxis 1-2 mg/kg PO; maximum 15 mg/day (up to 60-100 mg/d in 60adolescent)
Nelson Textbook of pediatrics, 18th Ed, 2008

Oral Iron: Doses

IAP: Treatment of IDA
The currently recommended dosage for infants & mg/kg/d, children is 3 mg/kg/d, higher doses are unnecessary, may increase side effects & reduce the patient compliance. Adolescents require 60 mg of elemental iron in case of mild anemia, and 120 mg/d (60v2) for moderate & severe (60v anemia. Therapy should continue for eight weeks after the blood values have returned to normal. Recent studies have documented the efficiency of weekly / twice weekly oral iron supplementation.

IAP Textbook of Pediatrics, 3rd Ed, 2006

Oral Iron: Doses

Conventionally, the dose recommended is 4-6 4mg/kg/day of elemental iron. However, smaller doses have been found to be equally effective & better tolerated. Hence a dose of 3 mg/kg/ day is currently recommended Absorptive capacity of iron in duodenum is saturated by 25 mg of elemental iron, hence higher doses will not increase the absorption Approximately 2 months treatment is required for Hb to come to normal level. Two more months therapy is required to replenish the stores
Indian Pediatrics 2008; 45:705-706 45:705-

Oral Iron: Doses

Children weighing 1530 kg can take half the average 15 adult dose, while small children & infants can tolerate relatively large doses of iron (e.g., 5 mg/kg). The dose used is a compromise between the desired therapeutic action and the adverse effects. It is always preferable to administer iron in the fasting state, state, even if the dose must be reduced because of GI side effects. Sustained high rates of red cell production require an uninterrupted supply of iron, and oral doses should be spaced equally to maintain a continuous high concentration of iron in plasma.
Goodman & Gilman's The Pharmacological Basis of Therapeutics - 12th Edition

Oral Iron: Doses

Duration of treatment is governed by the rate of recovery of Hb & the desire to create iron stores. The former depends 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 reconstituted within 12 months. Thus, an individual with an 1 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 10 g/dL may take only half that time. Much of the strategy of continued therapy depends on the estimated future iron balance. Patients with an inadequate diet may require continued therapy with low doses of iron. If the bleeding has stopped, no further therapy is required after the Hb has returned to normal. With continued bleeding, long-term therapy clearly is indicated. longGoodman & Gilman's The Pharmacological Basis of Therapeutics - 12th Edition

Oral Iron: Doses

NUTRITIONAL SUPPLEMENTATION IN LBW INFANTS
Iron supplementation is mandatory for all LBW infants Given as 2 mg/kg/d (Max 15 mg/d) Started when active erythropoiesis starts i.e. about 4 weeks of postnatal age (AAP: formerly 2 months) EPO therapy: Start iron at 2 mg/kg/d as soon as tolerated & increase to 4 mg/kg/d (6 mg/kg/d Optimum) (6 Optimum) when feeds reach 100 mL/kg; when at full feeds, begin preterm vitamins; if not on iron after 2 wk of rh-EPO rhtreatment consider: i.v. iron: as high as 15 mg/kg/d have been used to supplement neonate on EPO in the Tx of anemia of Prematurity
Feeding of Low Birth weight Infants, AIIMS- NICU protocols 2008, newbornwhocc.org AIIMS-

Oral Iron: Doses

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

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

Oral Iron: Doses

NUTRITIONAL SUPPLEMENTATION IN TERM INFANTS
Term infants should be sent home from the hospital on ironiron-fortified formula (2 mg/kg/d) if they are not breastfeeding To minimize the risk of iron deficiency anemia, all formulaformula-fed term infants should receive iron fortified formulas. Breastfed term infants should receive supplemental iron beginning when they are aged several months. Elemental iron supplementation 1 mg/kg/d should be provided to infants who are exclusively fed breast milk beyond 6 months of age. (or Iron supplemented formula: 12 mg/Litre): Rudolphs Peds, 21st Ed, 2002
Manual of Neonatal Care, 6th Ed, 2008, Cloherty, Eichenwald, Stark

Oral Iron: Doses

AAP Recommendation for Infants: Breastfed infants should be supplemented with 1 mg/kg per day of oral iron beginning at 6 months until iron-rich ironcomplementary foods (such as iron-fortified cereals) are ironintroduced. Formula-fed infants will receive adequate iron from Formulaformula and complementary foods. Whole milk should not be used before 12 months. (If used, risk of IDA, 1 mg/kg/d recommended) Infants ages 6 to 12 months need 11 mg of iron a day. When infants are given complementary foods, red meat and vegetables with high iron content should be introduced early. Liquid iron supplements can be used if iron needs are not met by formula and complementary foods.
http://www.aap.org/pressroom/Ironfinal.pdf, http://www.aap.org/pressroom/Ironfinal.pdf, October 2010

Choice of Milk for Feeding

Top Milk :
Term Breast Milk Cows Milk 67 3.2 4.1 4.4 120 90 0.2 70-220 700.76 5 Buffalos Milk 117 4.3 6.5 5.1 169 117 0.12 178 0.52 6 Goats Milk 72 3.3 4.5 4.4 134 111 0.05 185 0.50 1

Calories (Kcal/dl) Protein (gm/dl) Fat (gm/dl) Carbohydrate (gm/dl) Calcium (mg/dl) Phosphorus (mg/dl) Iron (mg/dl) Vitamin A (IU/dl) Sodium (mEq/dl) Folic Acid (mcg/dl)

67 1.1 4.5 7.1 33 15 0.03 250 0.8 5

Ref. : Deptt. of Agriculture, United States

Composition of various feeds

Mineral & Vitamin per 100 Kcal Calories (Kcal/kg/d) Protein (gm/kg/d) Carbohydrate (gm/kg/day) Calcium (mg) Phosphorus (mg) Iron (mg) PretermPretermRNI (AAPCON 1998) 105105-130 3.53.5-4 11-15.5 11175 91 1.7-2.5 1.7Preterm PretermPretermEBM (per 100 EBM + HMF ml) (Per 100 ml) 67 1.6 7.3 25 14 0.09 81 2 9.7 125 64 0.09 Preterm Formula (Per 100 ml) 80 2 9.1 128 64 0.8

Iron Supplementation in LBW



Although iron stores are low in preterm & term-SFDs, requirements are minimum in first few weeks of life! Birth weight e1000 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!
Journal of Neonatology, NNF-India, Vol. 18, No.1, Jan-Mar 2004

Oral Iron: Doses

Therapeutic Iron Trial A therapeutic iron trial is a trial of oral iron therapy without additional laboratory testing in a patient with a microcytic anemia and a history of dietary deficiency or known history of blood loss. An increase in the hemoglobin concentration of 1 g/dL or greater after 2 to 4 weeks of therapy confirms the diagnosis of iron deficiency. If the hemoglobin level does not increase, additional laboratory testing is necessary and other diagnoses should be considered!
5-Minute Pediatric Consult, 4th Edition, 2005

Oral Iron Therapy

Administration Best taken on an empty stomach 1 hour before or 2 hours after meals Take with a full glass of water (8 ounces or 240 milliliters) Avoid taking antacids, dairy products, tea, or coffee within 2 hours before or after this medication because they will decrease its effectiveness.

Oral Iron: Doses

Administration
To maximize the response to iron in an adult patient with moderate to severe IDA, a standard iron preparation should be given three to four times a day between meals. A fourth dose of iron at bedtime will help maintain iron delivery to the marrow during late evening & night hours. Otherwise, the serum iron can decline to iron-deficient ironlevels during the night, thereby dampening the marrow's proliferative response. response. Patients who are achlorhydric or who have had gastric surgery should be treated with iron elixir, because the removal of the tablet coat depends on normal stomach acidity.
Harrison's Principles of Internal Medicine, 14th Ed.,1998, Vol. 1, Pg 642

National Nutritional Anemia Control Program (NNACP)

Available data indicates that ferrous iron is absorbed 4-10 times better than ferric iron 4The daily dosage of Iron Folic Acid (IFA) supplement (20mg elemental iron + 100 mcg folic (20mg acid) acid) recommended for children 6-35 months for 6prophylaxis IFA supplementation should be done daily for minimum of 100 days in the first year of life and for minimum of 100 days in the second year of life

BreathBreath-holding Spells & Iron

Iron may reduce the frequency and severity of breathbreathholding attacks (or spells) in children but more research is needed to determine the extent of this effect. Spontaneously resolve by the time the child reaches seven years of age. The review of controlled clinical trials found that iron supplementation may reduce the frequency and severity of breath-holding attacks, particularly if the child is breathanemic. It is not known if this benefit is sustained after three months or if iron therapy should be continued until the child grows out of the breath-holding episodes. breathDose of 6 mg/kg/d v 4 months (IAP Chennai, 2004)

Malnutrition & Iron Therapy

Severely malnourished patients have a reduced ironironbinding capacity, they are neither able to withhold iron from invading organisms nor to prevent the toxic effects of iron itself. During the acute & intermediate phases of given, Tx iron should not be given, even in the presence of severe anemia. In the rehabilitation phase an iron supplement should be given. Children with kwashiorkor or marasmus should be assumed to be severely anemic. However, oral iron supplementation should be delayed until the child regains appetite and starts gaining weight, usually after 14 days
Textbook of Pediatric Gastroenterology & Nutrition, Stefans Guandalin, 1st ed, 2004

Malnutrition

Deworming & Iron

Where hookworms are endemic (prevalence 20-30% or 20greater) it will be most effective to combine iron supplementation with antihelminthic treatment to adults and children above the age of 2 years. Universal antihelminthic treatment, irrespective of infection status, is recommended at least annually. High-risk groups, annually. Highchildren, women and children, should be treated more intensively (2-3 times per year). The following single-dose treatments year). singleare recommended: Albendazole 400 mg single dose Mebendazole 500 mg single dose Levamisole 2.5 mg/kg single dose Pyrantel 10 mg/kg single dose

Infection & Iron Supplementation

Because one of the functions of elevated ferritin 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 infections. iron stores is seldom such an emergency situation that it cannot wait for any such acute infection to be treated.

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

Iron supplementation & Infection risk

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 ironfoods 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. Iron deficiency is associated with increased susceptibility to infection. However, excessive iron intake appears to be linked to oxidative stress and to more infections as well. Iron may help in combating infection by upup-regulating IL-1 production. Iron may predispose to infection by ILnourishing certain species of bacteria or by inhibiting the induction of nitric oxide synthase!
Indian Pediatrics 2008; 45:705-706, Nutrition in pediatrics 3rd ed, 2003 45:705-

Iron supplementation & Infection

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

5-Minute Pediatric Consult, 4th Edition, 2005

Important Points in Therapy

Folic acid should be added to the iron supplements to prevent folic acid deficiency anemia More scientific data is required on the magnitude of vitamin B12 and zinc deficiencies and the benefits of adding these micronutrients before their routine supplementation in conjunction with iron can be considered as public health intervention measure under NNACP Zinc has an inhibitory effect on iron absorption. However, this inhibitory effect lasts less than 30 minutes1
Nutrition Reseach, Volume 27, Issue 5, Pages 279-282 (May 2007) 279-

Important Points in Therapy

Strategies to minimize GI side effects Start at a lower dose and increase gradually over 4 to 5 days Giving divided doses or the lowest effective dose Taking supplements with meals Single daily dose at bedtime1 (empty stomach) Intolerance despite all measures, consider changing the preparation
Blood: principles and practice of hematology, Volume 1, By Robert I. Handin, Samuel E. Lux, Thomas P. Stossel

Important Points in Therapy

Strategies to minimize GI side effects Problems with constipation can be minimized by increasing water and fiber intake Aside from the unpleasant taste, intolerance to oral iron is uncommon in young children, although older children and adolescents sometimes have gastrointestinal complaints. Natural Way?: Pomegranate juice 0.2 Qg/cup, digestible iron. (0.3-1.2 mg/100 gm) (0.3Nelson Textbook of pediatrics, 18th Ed, 2008

Important Points in Therapy

Compliance in the first month of therapy is important as majority of iron absorption occurs during this period. It is continued for at least 2-3 2months after hemoglobin becomes normal, to replenish stores Iron supplementation may increase hemolysis if adequate vitamin E therapy is not supplied: Avoid use in premature infants until the vitamin E stores, deficient at birth are replenished1 stores,

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

Important Points in Therapy

With treatment, one must address the cause of IDA Control of infections: Iron deficiency anemia and infections are inter-linked. Recurrent interinfections can lead to anemia of chronic infections adding to the burden of iron deficiency anemia. Hence, infections should be treated energetically. Steps to prevent further occurrence of IDA
Indian Pediatrics 2008; 45:705-706 45:705-

Important Points in Therapy

While adequate iron medication is given, the family must be educated about the patient's diet, and the milk consumption should be limited to a reasonable quantity, preferably 500 mL (1 pint)/24 hr or less. This reduction has a dual effect: The amount of iron-rich foods is ironincreased. Excess intake of cow's milk leads to deficiency. Milk is a poor source of iron and very little iron present in cow's milk is not bioavailable. Cow's milk also produces blood loss & milk protein sensitive enteropathy (occult blood loss) in some. Iron present in breast milk is more bioavailable (49% Vs 10%) & is absorbed sue to the presence of lactoferrin.
Nutrition in Pediatrics 3rd ed, 2003

Important Points in Therapy

Since the calcium, phosphorous and magnesium contained in multivitamins can impair iron absorption, the iron content of these supplements should not be included in the therapeutic iron dose. For the same reason, the iron supplements & multivitamin should be taken at separate times Replacement therapy may begin as soon as iron deficiency is detected; however, it is essential to determine and correct the underlying cause Once anemia has corrected and iron stores have normalized; a low maintenance dose may be prescribed if an ongoing need for additional iron (e.g. menorrhagia, growth spurt). Dietary modification may also be considered. Consider similar supplementation for iron depleted but not anemic patients
Harrison's Principles of Internal Medicine, 14th Ed.,1998, Vol. 1, Pg 642

Some Common Preparations

Syr. Brand Vitcofol Hemsi Fortiron Vegefer Haem Up Dexorange Ped Tonoferon Pediatric Salt Fumarate Fumarate Sod. Feredetate (Ferric) Ferric Amm Citrate Ferric Amm Citrate Colloidal iron Elemental Folate B12 Iron/ 5 mL (mg) (Qg) 32.8 30 33 26 10.25 0.5 0.2 0.5 0.5 5 5 2.5 2 2.5
17% elemental iron

Misc.

Lysine, Cu, Zn, Mn

80 (250 mg 0.2
in Adult Prep)

Hepatoglob Peptonized ine Mikros iron

30

0.2

Some Common Preparations

Syr. Brand Faa 20 (Lupin) Globiron
(Aglowmed)

Salt Amino Acid Chelate IPC

Elemental Folate B12 Iron/ 5 mL (mg) (Qg) 15 50 0.5 -

Misc.

Ferium (Emcure) Hemfer (Alkem) Fe Glycine

SO4

16.7

0.17

2.5

Zn, Biotin

Some Common Preparations

Syr. Brand FeriumFerium-XT FeroniaFeronia-XT FerrochelateFerrochelate-XT Ferikind, Vitcofer OroferOrofer-XT Irozorb Irentia (Akumentis) Livogen JP Tone R.B. Tone Salt Ascorbate Elementa Folate l Iron/ 5 (mg) mL 30 0.5 B12 (Qg) Misc.

Ascorbate Ascorbate Gluconate Gluconate Gluconate

30 30 15 11.7 15

0.55 0.5 0.25 0.38 0.25

500 Qg Methylcobalamin

5 1.25

B6, Zn, Niacin Cal Lactate

Some Common Preparations

Syr. Brand Imferon Hemfer Kidicare Salt Carbonyl Elemental Folate Iron/ 5 mL (mg) 25 0.5 0.17 B12 (Qg) 6 2.5 Misc. eZn 11 mg Zn, Biotin
Zn, Mg, E, Lysine, B1, B2, B6, B12

Ferrous 16.7 glycine SO4 Ferrous 5 gluconate 33 13.3 8.8 1

Nutrifacts Fe Ferrous Gluconate Parnika Nicofer (Piramal) RichPro Zest, CHERI Ferric Amm Citrate Ferric Amm Citrate Choline Citrate

0.05 0.17 0.15

1.5 2.5 2.5

CuSO4, Vit C & A, Mo Zn, B6

Least Irritant

Zn, Mg, B1, B2, B6, B12 Several

Some Common Preparations

DROPS Brand Tonoferon Hepatoglobine Salt Colloidal Elemental Folate B12 Iron/ 1 mL (mg) (Qg) 25 0.2 0.2 0.2 0.1 5 4 4 Lysine 150 mg Misc.

Peptonized 20 10 10 10 8

Ferrochelate XT Ascorbate FeroniaFeronia-XT Irentia OroferOrofer-XT Hemsi Vegefer Ascorbate Ascorbate Sod. Feredetate

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

Some Common Preparations

Tab. Brand Livogen XT Feronia XT Ferium XT Irozorb Orofer XT Cap. Vitcofol Tab. Aloha HbFast Z Cap. Imferon Tab. Ferronine (gsk) Salt Ascorbate Ascorbate Elemental Folate B12 Iron/ tab (mg) (Qg) 100 100 1.5 1.5 Misc. eZn 22.5 mg -

Ascorbate Fumarate Carbonyl

100 100 100

1.1 0.75 1.5

7.5 15 eZn 7.5 mg, B6 Zn, Vit. C

Ferrous bis 60 glycinate

eZn 15 mg

Summary
 In terms of efficacy all available iron preparations are effective though timing of response may vary  Iron supplements should be prescribed in right form, dose & duration  Cause of IDA should be addressed whenever possible

Thanks