Newer iron preparation

6 years/ male

Came for non responding anaemia Hb 3 months ago was 6.5, started on Iron lll polymaltose complex, Hb after 3 months was 7.2. Compliance checked, no occult loss of blood from GIT or other sources Put on oral ferrous salt , marked symptomatic improvement within 1 week, Hb 9.3 in 3 weeks Subsequent reports of poor efficacy of IPC .

Scope of the talkWhat is new y Pediatricians perspectivey

Different hatsy y

y

In practice we wear different hats Assume role of neonatologist, pulmonologist, hematologist, intensivist etc Above all general pediatrician

Pediatricians haty

pediatrician

y

Focus on iron preparations commonly used in practice Some information about Intravenous iron preparations

What is new?

Discuss about Iron lll polymaltose complex, ferrous ascorbate, carbonyl iron

13 or more saltsy y

y

Not unlike medical degrees Add ferrous /ferric & any compound = new iron salt Why so many preparations needed

Iron absorption foundation factFe 2+

Ferrous sulfate

Why is new needed

the standard effective , economical, easy to administer Iron is absorbed in ferrous form fumarate, gluconate, succinate,lactate, glutamate Ferrous sulfate unstable in liquid form hence sorbitol based preparations Fumarate is tasteless, poorly water soluble but soluble in acidic medium of stomach

Why newer salts are needed 5 Ps

Poor absorption: food (Phytates), antacids inhibit Poor compliance: ~30% are recorded poor compliant Poor tolerance Prolonged therapy of at least 3 months needed Poisoning potential: mucosal barrier is overwhelmed with larger doses

Newer iron salts

Complexed with chelators to decrease side effects; sodium feredetate Combined with absorption enhancer : ascorbate More tolerability due to small particle size; carbonised Fe Have different mechanism of absorption Many have been tried as food fortifiers & not as medicine Scanty data in standard journals, not many non sponsored articles

Iron lll polymaltose complex

Not strictly newer iron Iron in ferric form gets absorbed with help of two ligands Absorption resembles natural process of iron absorption from intestine Less side effects & less teeth staining As absorption depends on ligands. In overdose saturation of ligands prevents excessive absorption.

Held promise butReports of failure of Hb rise in many preparations y Probably dependent on pH and other physical properties of the preparation. y Report by Mehta et al(ref: ineffectiveness of ironypolymaltose in treatment of iron deficiency anemia.J Assoc Physicians India 2003:51,419-421)

Carbonyl iron

Very small ,uniform particles of pure iron in pure metallic form In stomach acid reduces iron to ferrous (ionic ) form Absorption is self limited & slow depends on rate of gastric acid secretion Antacids , milk, food interfere with absorption Similar effectiveness as FS in pregnant women, no study on children

Carbonyl ironDoes not change colour or flavour of food y Mainly used as food fortifier in wheat floor y Certain issues about bioavailability in humans Ref:Low bioavailability of carbonyl iron in man:ystudies on iron fortification of wheat fIour13 LeifHallberg, MD, Mats Brune, MD, and Lena Rossander, Dr Med Sc Am JC/in Nuir l986;43:

Ferrous ascorbateCombination of ascorbic acid with ferrous iron y Iron absorption enhancer y Probably also helps in incorporation of absorbed iron into Hb. y Known as reference iron in US y Many studies in pregnant women y Can cause some GI intolerancey

Ferrous bis-glycinate bis

Iron amino acid chelate Came as food fortifier Less irritant to stomach 20%elemental iron High bioavalability in presence of inhibitors Good safety potential Studies document comparative efficacy as ferrous ascorbate Other in group ferrous Glycine sulphate

Sodium fereditateContains iron in an un-ionised form. y Iron is insulated or sequestered with the EDTA to form a chelate. y Not astringent and does not discolour teeth. y Iron absorption is enhanced in irondeficiency states. y Tastes better, can be mixed with fruit juices or milky

Preparations with additionsAddition of ascorbic acid to iron preparations increase iron absorption y Stability of ascorbic acid is issue y Optimum ratio of ascorbic acid & FS varies as per amount of inhibitors in diet. y Trace element, vitamins & other hematinics do not increase response to ferrous salt(Nelsons text book) and are irrationaly

Microencapsulated form

Once a day as sprinkler fortifying diet is as effective as TDS FS in treatment of anaemic children in Ghana. American Journal ofClinical Nutrition,Vol. 74, No. 6, 791-795, December 2001

Ferrous fumarate with ascorbic acid Most food fortification is for prevention Future of anaemia treatment. RefEur J Clin Nutr.2009 Mar;63(3):437-45. Epub 2007 Dec 19. Multiple micronutrient fortification of salt. Vinodkumar M, Rajagopalan S

At one glancename Eleme ntal iron 20% 50 % asborb ed* 27 ~4-50 7-11 20-40 75 20% GIT SE ++ + + +/Teeth stainin g + + + Phytat es + Toxic potenti al + effect ivene ss + +/+/+ + + FeSO4 IPC Carbonyl Ferrous asorabate Naferedetate Ferrous bis glycinate

Summary of oral iron preparationsy y y y y y

Most of them are effective newer iron preparations have better safety profile.(lesser toxic potential than FS ) Some of them may not give consistent Hb rise More expensive Use any but monitor effectiveness Be on look out for microencapsulated form.

Monitoring effectiveness

Rise of Hb @ 0.1mg/dl/day ~2gm/dl after 3 weeks What if not effective: compliance is major issue The etiology not properly looked into (e.g. GI bleed) Associated systemic inflammatory disease Wrong diagnosis Very poor absorptive capacity: celiac disease

Parentral ironIM or IV Iron dextran, sodium ferric gluconate, Iron sucrose Some newer forms are under study :ferroxybutol Supposed uses in end stage renal disease (ESRD), preterm babies along with EPO, in patients with IBD & other rheumatological conditions Patients poorly compliant to oral iron therapy or who do not record Hb rise after 3 months of at least 2 different oral salts

Parentral iron: basic factsIncreases iron store rapidly y Rate of HB rise is similar to oral iron y Some studies have documented faster rise of Hb ( within 1 week) of initiation y Can be one indication . When faster rise of Hb is desired e.g. pre-operative patients. y Shorter course (2-3 days) with iron sucrose is described.y

Intravenous ironSome chance of life threatening anaphylactic reaction, least with iron sucrose. y Iron sucrose is with least potential to have serious side effects y Transient hypotension, facial flushing, pruritis and pica!!! y In pre terms rise of ferritin is described. (may be indicative of oxidative injury)y

Parentral iron preparationsIM : high adverse effects , skin tattooing, serum sickness like reaction, anaphylaxis y Discontinued in US, UK 5-6 years agoy

Practical utility for usNot much used at least in Mumbai by pediatric nephrologists, rheumatologist & hematologist y May be indicated : only occasional patient who is intolerant to oral iron or where faster Hb rise is desirable preop ( decreases need for blood transfusions)y

To concludeIV iron is only occasionally used in every day clinical practice y Out of many iron preparations available choose according to cost , tolerability, effectiveness ( elemental iron content & % of iron absorbed) y Monitor response to the therapyy

Sincere thanks to

Dr Ratna Sharma : Pediatric hemat,Mumbai Dr Khubchandani: Ped rheumatolgist, mumbai Dr Pankaj Deshpande: Ped Nephro, mumbai Dr Prakash Vaidya y For sharing their experience & thoughts

Thank you