Is iron deficiency increasing your patient’s risk for environmental toxicity? Petra Eichelsdoerfer, ND, CN, RPh New Hampshire Association of Naturopathic.

Is iron deficiency increasing your patient’s risk for

environmental toxicity?

Petra Eichelsdoerfer, ND, CN, RPh

New Hampshire Association of Naturopathic Doctors

Fall Seminar, Nashua, NH

November 2, 2013

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Objectives:• Review the manifestations, diagnosis, and monitoring parameters of

iron deficiency

• Discuss the metabolic changes induced by iron deficiency, including changes in

• Energy production• Gastrointestinal absorption of iron, lead, and other minerals• Hepatic biotransformation of xenobiotics

• Emphasize treatments of iron deficiency, including • Dietary changes to enhance iron absorption• Botanical, nutritional, and nutraceutical supplements useful for iron deficiency• Parenteral iron products

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Who is at risk?• Infants & children between 6 months – 4 years

• Adolescents

• Pregnant woman

• Chronic blood loss, including menstrual losses and blood donation• 500 ml donated blood 200 – 250 mg iron

• Celiac disease

• Helicobacter pylori infection• Risk applies whether bleeding present or not

• Gastric bypass and some duodenal switch patients• Bypasses part or all of duodenum/jejunum where iron best absorbed

• Vegetarians• RDA for vegetarians

• 14 mg/day adult men, postmenopausal women• 33 mg/day premenopausal women• 26 mg/day adolescents

• Regular intense exercise, especially runners• May need up to 30% more iron than RDA

Linus Pauling Institute, http://lpi.oregonstate.edu

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Iron deficiency in a nutshell• Tissue iron deficiency occurs before RBC levels reach anemia levels.

• As insufficiency progresses to deficiency, • Increases in

• Iron, lead, and other divalent cation absorption

• Reduction in • Synthesis of energy production enzymes• Synthesis of hepatic and intestinal biotransformation enzymes• Cellular turnover

• Patients experience increased• Glucose sensitivity• Environmental toxicity• Foggy thinking• Fatigue

• Anemia

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Iron Deficiency: Diagnosis & Monitoring

• Gold standard: Marrow biopsy/smear with iron stain• Increasingly, serum or plasma ferritin relied upon

• Virtually all patients with ferritin < 10 – 15 ng/mL are iron deficient• Sensitivity 59%, specificity 99%

• 25% women with absent stainable marrow iron had ferritins > 15 ng/mL• Setting cutoff at 30 – 40 ng/mL better diagnostic efficiency

• Sensitivity 92 – 98% (respectively), specificity 98% (both)

• Presumptive: • Total iron binding capacity• Serum iron• RBCs, hemoglobin, hematocrit

UpToDate, www.uptodate.com

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Normal body iron content• 2 grams: Hemoglobin circulating in RBCs

• 400 mg: Iron-dependent proteins• Myoglobin, cytochromes, catalases, etc

• 3 – 7 grams: Plasma iron bound to transferrin

• Balance: Iron stored as either ferritin or hemosiderin• Adult men ~ 10mg/kg• Adult women, ages 20-45 years

• 93% ~ 5.5 + 3.4 mg/kg; 7% iron deficit 3.9 + 3.2 mg/kg• Up to 20% pre-menopausal women in US have absent iron stores

• Of note: ~ 60 mg found in brain• Ferritin, transferrin, iron-dependent enzymes

UpToDate, www.uptodate.com Beard & Han. Systemic iron status. Biochimica et Biophysica Acta (BBA) - General Subjects 2009; Vol 1790(7): 584 – 588

Changes in functional pools of iron at various stages of iron status• Depletion of iron storage

• Also known as tissue iron deficiency• Stores depleted• Functional iron supply not limited

• Early functional iron deficiency• Supply of functional iron low enough

to impair RBC formation• Reduced function of iron-deficient

enzymes• NOT low enough to cause

measurable anemia

• Iron-deficiency anemia• Inadequate iron to support normal

RBC formation• Sub-optimal function of iron-

dependent enzymes• Microcytic, hypochromic RBCs• Elevated HbA1C

Beard J L J. Nutr. 2001;131:568S-580S©2001 by American Society for Nutrition

Linus Pauling Institute, http://lpi.oregonstate.edu

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Iron deficiency: Symptoms• Anemia:

• Fatigue, rapid heart rate, palpitations, and rapid breathing on exertion.

• Impaired athletic performance and physical work capacity• Decreased oxygen delivery to active tissues (decreased hemoglobin)• Limited oxygen uptake by muscle cells (reduced myoglobin)• Impaired oxidative metabolism in mitochondria

• Decreased cytochromes, other iron-dependent enzymes for electron transport, ATP synthesis

• Lactic acid production increased (increased reliance upon glycolysis)

• Impaired ability to maintain normal body temperature

• Severe iron-deficiency anemia • Nail changes (brittle, spoon-shaped)• Sores at the corners of the mouth, taste bud atrophy, and a sore tongue. • Advanced cases: dysphagia due to formation of tissue webs in throat and

esophagusSource: Linus Pauling Institute, http://lpi.oregonstate.edu

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Iron and the brain• Iron concentrated in brain cells

• Distinct distribution pattern within brain, primarily in oligodendrocytes • Transferrin and ferritin• Transferrin receptors on neurons, blood vessels

• Many iron-dependent pathways• Myelination• Neurotransmitter synthesis (cofactor)• Mitochondrial ATP sythesis

• Deficiency effects • Dietary iron deficiency decreased protein synthesis • Infant deficiency may learning, memory, visual acuity, movement deficits in grade

school• Iron deficient mothers more negative, less engaged, & responsive toward infants• Iron repletion improved postpartum depression, stress, cognitive function• Brain slow to restore normal ferritin levels after repletion, relative to other tissues (rats)

Beard & Han. Systemic iron status. Biochimica et Biophysica Acta (BBA) - General Subjects 2009; Vol 1790(7): 584 – 588

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Intestinal absorption of non-heme iron• Primarily in duodenal and upper jejunal brush border

• Non-selective (iron-dependent) carrier• Other divalent minerals may influence iron absorption

• Transporter less regulated, so excess intake may iron overload

• Iron must be in ferrous (II) form for absorption

Kim, et al., J Med Food 2006: 231 – 236; Linus Pauling Institute; http://lpi.oregonstate.edu Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Intestinal absorption of heme ironHeme iron (10-15% total iron intake; ~ 33% iron absorbed)

• Found as hemoglobin and myoglobin in animal source foods

• Soluble in alkaline environment

• Transporters located in brush border of duodenum, also hepatocytes

• Selective, regulated according to iron level in body

Kim, et al., J Med Food 2006: 231 – 236; Linus Pauling Institute; http://lpi.oregonstate.edu Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Regulation of intestinal iron uptakeHeme iron• Selectively taken up by heme iron transporter (HCP)• Endocytosed• Ferrous (II) iron liberated

Non-heme iron• Ferric (III) iron reduced to ferrous (II) form by vitamin

C in the gut lumen or membrane ferriredutases (e.g., duodenal cytochrome B, DCYTB)

• Ferrous (II) iron enters apical membrane via divalent metal-ion transporter (DMT1)

• Driven by acidic microclimate and H+ electrochemical gradient

Transport into circulation• Ferrous (II) iron transported to transferrin in blood • Ferroportin 1 mediates transfer, in association with

hephaestin

Regulation – if iron stores sufficient• Hepcidin binds to ferroportin 1 internalization and

degradation of ferroportin 1• Hepcidin synthesized by liver when iron stores

adequate

• Decreases iron transfer out of enterocyte

Zimmermann, Michael B, Dr,Hurrell, Richard F, PhD - Lancet, The - Volume 370, Issue 9586, 511-520 © 2007 Elsevier Ltd

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Iron dependent enzymes• Heme containing

• Cytochrome P450 family• Hormone and xenobiotic metabolism• Electron transport, ATP synthesis• 50% of heme synthesized used for P450 enzymes

• Catalase, peroxidases• Protect against reactive oxygen species (ROS) • Myeloperoxidase secreted by neutrophils as part immune response

• Non-heme containing• NADH dehydrogenase• Succinate dehydrogenase• Lipoxygenases• Iron responsive element binding proteins (IRE-BP)• Thyroid peroxidase (thyroid hormone synthesis)• Ribonucleotide reductase (DNA synthesis)

Source: Linus Pauling Institute: http://lpi.oregonstate.edu

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Iron deficiency alters enzymatic activity (rats)Non-specific defense against xenobiotics• Hydrophobic compounds rendered more hydrophilic, allowing elimination• Cytochrome P450 complex (P450) • NADPH cytochrome P450 reductase (P450-RED)

• Both enzymes present in liver, intestines• Intestinal activity inhibited in mild, moderate, and severe iron deficiency states

• Suggests that intestinal activity dependent upon iron presence in intestinal lumen

• Liver activity unchanged

• Glucose-6-phosphate dehydrogenase (G6P-DH)• 6-Phosphogluconate dehydrogenase (6PG-DH)

• Catalyze first two steps of NADPH synthesis via pentose-phosphate pathway, most active in liver• Both enzymes present in liver, intestines, RBCs• Intestinal activity level unchanged in iron deficiency • Liver activity level of 6PH-DH reduced in severe iron deficiency• RBC activity level of both enzymes increased in moderate and severe iron deficiency

• However, since fewer RBCs, overall, less activity compared to healthy stateDhur, et.al., J Nutr 119: 40 - 47, 1989

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Iron deficiency and thyroid function

• Blunts thyrotropic response to exogenous TRH

• Lowers serum T3 and T4 levels, especially T3

• decreased hepatic production of T3 because of reduced hepatic thyroxine-59-deiodinase activity

• Lowers utilization of thyroid hormones (as evidenced by slower turnover of T3 and reduced T3 nuclear binding).

Zimmermann MB, et al., Thyroid. 2002 Oct;12(10):867-78.

Source: http://upload.wikimedia.org/wikipedia/commons/8/82/Thyroid_hormone_synthesis.png

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Iron deficiency increases absorption of other minerals

• Differs by origin of iron deficiency

• Dietary iron deficiency enhances the absorption of• Iron, cobalt, manganese, zinc, cadmium and lead

• Iron deficiency due to bleeding increases the absorption of• Iron, cobalt and perhaps manganese.

Flanagan, et. al., J Nutr 110:1754-1763, 1980

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Iron Deficiency: Treatment

• Dietary changes to enhance iron absorption

• Botanical, nutritional, and nutraceutical supplements useful for iron deficiency

• Parenteral iron products

Source: Linus Pauling Institute, http://lpi.oregonstate.edu18

Iron: Recommended Dietary AllowanceLife Stage Age  Males (mg/day) Females (mg/day)

Infants 0-6 months 0.27 (AI) 0.27 (AI)

Infants 7-12 months 11 11

Children 1-3 years 7 7

Children 4-8 years 10 10

Children 9-13 years 8 8

Adolescents 14-18 years 11 15

Adults 19-50 years 8 18

Adults 51 years and older 8 8

Pregnancy all ages - 27

Breast-feeding 18 years and younger - 10

Breast-feeding 19 years and older - 9

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Food sources of iron

• Heme iron (richest in highly perfused tissues)• ~ 40% bioavailable • Organ meats: liver, kidney, heart• Red meat: Beef, venison• Dark meat: poultry, pork, fish• Light meat: poultry

• Non-heme iron • 5 – 10% bioavailable• Blackstrap molasses• Green leafies: spinach, kale, swiss chard, etc.•

Beard & Han, Systemic iron status. Biochimica et Biophysica Acta 2009; 1790: 584 – 588Linus Pauling Institute, http://lpi.oregonstate.edu

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Iron content of foodsFood Serving Iron content (mg)Beef 3 ounces*, cooked 2.32

Chicken, dark meat 3 ounces, cooked 1.13

Oysters 6 medium 5.04

Shrimp 8 large, cooked 1.36

Tuna, light 3 ounces, canned 1.30

Black-strap molasses 1 tablespoon 3.50

Raisin bran cereal 1 cup, dry 5.79-18.00

Raisins, seedless 1 small box (1.5 ounces) 0.81

Prune juice 6 fluid ounces 2.28

Prunes (dried plums) ~ 5 prunes (1.7 ounces) 0.45

Potato, with skin 1 medium potato, baked 1.87

Kidney beans 1/2 cup, cooked 1.97

Lentils 1/2 cup, cooked 3.30

Tofu, firm 1/4 block (~1/3 cup) 2.15

Cashew nuts 1 ounce 1.89Source: Linus Pauling Institute: http://lpi.oregonstate.edu *3-oz serving of meat is ~ size of a deck of cards.

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Enhancing absorption

• Non-heme iron absorbed more effectively if consumed with acids:• Vinegar• Vitamin C• Lemon juice

• Consume non-heme iron with animal source proteins (need not be high in iron)

• e.g., greens with chicken, fish

• Cook acidic foods in cast iron • e.g., greens with lemon juice, marinara sauce

• Guava enhances absorption of non-heme iron in adolescents [Nair, et al., J Nutr. 143: 852-858, 2013]

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Inhibiting absorption• Phytic acid (phytate)

• Legumes, grains, rice• Believed to bind to non-heme iron, limiting absorption • 5 – 10 mg phytate may 50% or more reduction in non-heme iron absorption• Estimated absorption from legumes ~ 2%

• Polyphenols• Fruits, vegetables, coffee, tea, wines, spices• Vitamin C reduces effect of polyphenols on absorption

• Soy protein• Independent of soy’s phytate content

• Summary• High fiber diets tend to have lower iron bioavailability• Lower fiber diets have higher iron bioavailability

• Particularly if high in heme iron sources

Source: Linus Pauling Institute: http://lpi.oregonstate.edu

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Nutrient InteractionsVitamin A

• Vitamin A deficiency may exacerbate iron-deficiency anemia

• Supplementing both greater improvement in anemia than either nutrient alone.•

Copper

• Copper may play a role in iron absorption

• Required for normal iron metabolism, RBC formation

• Copper deficiency microcytic anemia

Zinc

• High dose iron supplements on an empty stomach may decreased zinc absorption

• Iron supplements do NOT inhibit zinc absorption when taken with food

Calcium

• Calcium decreases absorption of heme and nonheme iron if taken at same mealSource: Linus Pauling Institute: http://lpi.oregonstate.edu

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Botanicals and iron

• Whole food complexed iron• Source: leafy greens, microbial cultures, or other botanicals• Source may not be clearly indicated

• Dandelion (leaf and root)

• Yellow dock

• Alfalfa

• Stinging nettle

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Supplementing Iron: Adverse effects

• Directly correlated with unabsorbed iron content• Nausea, vomiting• Intestinal cramping, bloating, gas• Constipation, diarrhea

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Enhancing the body’s utilization of iron

• Iron cell salts• Unlikely to restore depleted iron stores

• Foods traditionally used as blood builders• Liver• Beet root

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Non-heme iron supplements: Conventional forms

• Ferrous sulfate (20% elemental iron by weight)• Typical dose: 325 mg QD - TID

• Ferrous gluconate (12% elemental iron by weight)• Typical dose: 325 mg QD - TID

• Ferrous fumarate (33% elemental iron by weight)• Typical dose:

• Polysaccharide iron complex (up to 200 mg elemental iron/capsule)• Typical dose: 150 mg elemental iron QD - TID

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Non-heme iron supplementsCommon natural medicine forms• Amino acid chelates

• Glycinate, bis-glycinate, tris-glycinate• Aspartic acid

• Tricarboxylic acid cycle intermediates• Ferrous succinate• Ferrous citrate

• Iron protein succinylate

• Iron carbonyl (pure iron micro particles)

• Iron peptonate

• Ferric salts• Ferric pyrophosphate• Ferric ammonium citrate

• Ferritin

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Non-heme iron supplementation - Dosing

• Expressed as mg elemental iron

• Varies with severity of deficiency

• Lower doses ~ 30 mg daily

• Higher doses 100 – 150 mg, up to 200 mg daily • Usually in divided doses

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Heme iron supplementation• Liver fraction

• Ex. Energizing Iron, Energizing Iron with Eleuthero (Integrative Therapeutics)• 1 mg elemental iron/cap• Recommended dose: 2 capsules TID

• Heme iron polypeptide (HIP)• Source: Hemoglobin (bovine)• Ex. Proferrin ES, Proferrin Forte (Colorado Biolabs)

• 12 mg elemental iron/tab• Recommended dose: 1 tablet up to TID• RCT showed no significant safety or efficacy benefits of HIP BID over ferrous sulfate

controlled release BID1

1. Barraclough, et al.Nephrol Dial Transplant 2012 Nov;27(11):4146-53

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Parenteral iron repletion

• Iron dextran (InFed, Dexferrin)

• Iron sucrose

• Ferric carboxymaltose

• Ferumoxytol

• Sodium Ferric Gluconate Complex

• Note: ALL associated with severe hypersensitivity reactions, including anaphylaxis. Pre-treatment with diphenhydramine commonly used

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Iron Dextran (Infed, Dexferrum)• Safety differs by molecular weight

• High molecular weight: Dexferrum• Associated with much higher rates of serious or life-threatening adverse reactions• Removed from formulary by US Veterans Administration, other organizations for safety reasons

• Low molecular weight: Infed• Severe, life-threatening adverse reactions far more rare (< 1:200,000)

• Indication: Documented iron-deficiency in patients for whom oral administration is unsatisfactory or impossible

• Route: IM (Infed only), IV (both Infed and Dexferrum) • Test dose (IV push) required before administration • Pre-treatment very common

• Dphenhydramine• Glucocorticoid pretreatment recommended if history of asthma or > 1 drug allergy

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx UpToDate; www.uptodate.com

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Iron Dextran (Infed, Dexferrum)Dosing in iron deficiency anemia

• 1 ml iron dextran = 50 mg elemental iron

• Goal is restoration of hemoglobin AND iron store replenishment

• Dose calculated several ways – for example

Dose (mL) = 0.0442 (desired Hb − observed Hb) × LBW + (0.26 × LBW)

Based on: desired Hb = the target Hb in g/dL.

Observed Hb = the patient's current hemoglobin in g/dL

LBW = lean body weight in kg For males: LBW = 50 kg + 2.3 kg for each inch of patient's height over 5 feet

For females: LBW = 45.5 kg + 2.3 kg for each inch of patient's height over 5 feet

Note: Use patient's lean body weight (or actual body weight if less than lean body weight) when determining dosage.

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Table for estimating total iron dextran required for restoring Hb & Iron Stores

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

Patient mL requirement of iron dextran injection based on observed hemoglobin of:LBW (Kg) 3 g/dL 4 g/dL 5 g/dL 6 g/dL 7 g/dL 8 g/dL 9 g/dL 10 g/dL

5 3 3 3 3 2 2 2 210 7 6 6 5 5 4 4 315 10 9 9 8 7 7 6 520 16 15 14 13 12 11 10 925 20 18 17 16 15 14 13 1230 23 22 21 19 18 17 15 1435 27 26 24 23 21 20 18 1740 31 29 28 26 24 22 21 1945 35 33 31 29 27 25 23 2150 39 37 35 32 30 28 26 2455 43 41 38 36 33 31 28 2660 47 44 42 39 36 34 31 2865 51 48 45 42 39 36 34 3170 55 52 49 45 42 39 36 3375 59 55 52 49 45 42 39 3580 63 59 55 52 48 45 41 3885 66 63 59 55 51 48 44 4090 70 66 62 58 54 50 46 4295 74 70 66 62 57 53 49 45

100 78 74 69 65 60 56 52 47105 82 77 73 68 63 59 54 50110 86 81 76 71 67 62 57 52115 90 85 80 75 70 64 59 54120 94 88 83 78 73 67 62 57

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Iron Dextran (Infed, Dexferrum) Dosing after acute blood loss

• Goal: Restoration of iron lost due to bleeding

• Replacement iron (in mg) = blood loss (in mL) × hematocrit

• 1 ml iron dextran = 50 mg elemental iron

• Assumption: 1 ml normocytic, normochromic RBCs contains 1 mg elemental iron

• Example: • Blood loss of 500 mL with 20% hematocrit. • Replacement iron = 500 × 0.2 = 100 mg• Iron dextran dose = 100 mg/50 = 2 mL

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Iron Sucrose (Venofer)• What it is:

• Aqueous complex of polynuclear iron (III)-hydroxide in sucrose• Dissociates into iron and sucrose; Iron transported as complex with transferrin to target cells

• Indication: Iron-deficiency anemia in patients with chronic kidney disease

• Route: IV • Slow IV injection (undiluted), over 2 – 5 minutes• IV injection or infusion, diluted with NaCl 0.9% to concentration of at least 1 mg/ml

• 1 ml iron sucrose = 20 mg elemental iron• Usual dosage, adults

• Non-hemodialysis kidney disease patients: • 200 mg on 5 different occasions in 14 day period• 500 mg on days 1 and 14, diluted in max 250 ml NaCl 0.9% infused over 3.5 – 4 hours

• Hemodialysis patients: 100 mg per consecutive hemodialysis sessions, total treatment = 1000 mg• Peritoneal dialysis patients: 300 mg IV infusion over 1.5 hours X 2, 14 days apart, followed by 400 mg infusion over 2.5 hours X

1, 14 days later

• No well-established max dose for approved indication in adults• Usual dosage, children > 2 years

• 0.5 mg/kg IV q 2 weeks, for 12 weeks, undiluted by slow IV injection over 5 minutes or diluted in 25 ml NaCl 0.9% over 5 – 60 minutes

• Max dose in children > 2 years = 100 mg/doseSource: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Iron Sucrose (Venofer)• Monitoring and adverse effects

• Hypotension: Monitor BP during and immediately after administration:• May occur immediately after injection, within 30 min• May be related to administration rate and/or total dose

• Evaluate hematologic response at least one month after administration• Transferrin saturation rises rapidly after administration • Do not evaluate serum iron measures for at least 48 hours

• Hypersensitivity reactions - Be prepared for possibly severe reactions• Monitor for at least 30 minutes after administration, & until patient clinically stable• Anaphylaxis, shock, significant hypotension, loss of consciousness, collapse

• Other adverse reactions • Nausea, vomiting, diarrhea, headache, BP changes (hyper- or hypotension),

cramping, myalgias

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Ferric Carboxymaltose (Injectafer)• What it is:

• Colloidal iron (III) hydroxide in complex with carboxymaltose (carbohydrate polymer)• Allows for iron uptake reticuloendothelial system without release of free iron

• Indications: Iron-deficiency anemia in adults, with or without chronic kidney disease

• Route: IV • Slow IV push (undiluted) ~ 100 mg/min• IV infusion (dilute to 2 mg/ml or more using NaCl 0.9%)

• 1 ml ferric carboxymaltose = 50 mg elemental iron• Usual dosage, weight > 50 kg

• 750 mg elemental iron on day one, repeat after at least 7 days• Max dosage per treatment course = 1500 mg elemental iron (cumulative)

• Usual dosage, weight < 50 kg• 15 mg/kg on day one, repeat after at least 7 days• Max dosage per treatment course = 1500 mg elemental iron (cumulative)

• Max iron levels (37 – 333 mcg/ml) reached in 0.25 – 1.2 hoursSource: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Ferric Carboxymaltose (Injectafer)• Adverse effects

• Monitor BP during and immediately after administration:• BP elevations, usually transient, resolving within 30 min• May be accompanied by facial flushing, dizziness, nausea

• Hypersensitivity reactions - Be prepared for possibly severe reactions• Monitor during and for at least 30 minutes after administration, and until patient

clinically stable• Anaphylaxis, shock, hypotension, loss of consciousness, collapse

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Ferumoxytol (Feraheme)• What it is:

• Superparamagnetic iron oxide, coated with carbohydrate shell• Enters reticuloendothelial system intact

• Indications: Iron-deficiency anemia in adults with chronic kidney disease

• Route: IV • IV injection (undiluted), rate up to 1 ml/second (30 mg/second)

• 1 ml ferumoxytol = 30 mg elemental iron (510 mg/17 ml vial)• Usual dosage = 510 mg IV, followed by 510 mg IV 3 – 8 days later• Maintenance dose: May re-administer recommended dose in persistent or

recurrent iron deficiency anemia

• Max concentration levels (mean = 206 mcg/ml) reached in ~ 20 minutesSource: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Ferumoxytol (Feraheme)

• Monitoring and adverse effects• Monitor BP during and immediately after administration:

• Hypotension may occur immediately after injection, within 30 min

• Evaluate hematologic response at least one month after administration• May interfere with MRI for three months after administration

• Hypersensitivity reactions - Be prepared for possibly severe reactions• Monitor for at least 30 minutes after administration, & until patient clinically stable• Anaphylaxis, syncope, unresponsiveness, reported in 0.2% • Less severe hypersensitivity reactions (3.7%) – rash, pruritis, urticaria, wheezing

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Sodium Ferric Gluconate complex (Ferrlecit, Nulecit)• What it is:

• Stable, macromolecular complex • Iron transferred to transferrin before update by target tissues

• Indication: Iron-deficiency anemia in patients with chronic kidney disease, on hemodialysis and epoetin

• Route: IV • Adults: Slow IV injection (undiluted), or diluted with 100 ml NaCl 0.9%• Children: IV infusion, diluted with 25 ml NaCl 0.9%

• 1 ml sodium ferric gluconate complex = 12.5 mg elemental iron (5 ml vial = 62.5 mg elemental iron)• Usual dosage, adults and children > 15 years

• 125 mg IV per infusion. • Most patients will require total cumulative dose of 1000 mg, divided into 8 dialysis sessions• Doses > 125 mg/infusion assocated with higher incidence and/or severity of adverse effects

• No well-established max dose for approved indication in adults

• Usual dosage, children 6 – 15 years • 1.5 mg/kg/dose, administered by IV infusion• Max dose in children 6 – 15 years = 125 mg/dose

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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Sodium Ferric Gluconate complex (Ferrlecit, Nulecit)

• Monitoring and adverse effects• Monitor BP during and immediately after administration:

• Hypotension may occur during or within 30 minutes after administration, usually resolves within 1 – 2 hours

• Evaluate hematologic response at least one month after administration

• Hypersensitivity reactions - Be prepared for possibly severe reactions• Monitor for at least 30 minutes after administration, & until patient clinically stable• Anaphylaxis, shock, hypotension, loss of consciousness, collapse• Less severe hypersensitivity reactions – flushing, chills, dyspnea/chest pain, rash• Other adverse reactions – dizziness, muscle cramping, flu-like syndrome,

tachycardia, erythrocyte morphology changes

Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx

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In summary, iron deficiency• Increases absorption of other divalent cations, including potentially toxic

metals, e.g., lead

• Decreases the intestinal wall capacity to metabolize hydrophobic xenobiotics, thereby increasing systemic absorption

• Impairs liver capacity for clearing hydrophobic xenobiotics

• Impairs thyroid hormone synthesis, clear cognition, tissue healing, and epithelial health

• Increases glucose sensitivity and HbA1c values

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So if your patient has possible environmental toxicity, foggy thinking,

glucose sensitivity, or possible steroid or thyroid hormone imbalance…

Check for iron deficiency and treat that simultaneously

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END

Questions?

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Thanks!

Contact information

Petra Eichelsdoerfer, ND, CN, [email protected]

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Helpful resources: Free & Government

• Daily med (http://dailymed.nlm.nih.gov)• Package inserts for many prescription medications

• Food and Drug Administration (FDA) (www.fda.gov)

• Centers for Disease Control and Prevention (CDCP) (www.cdc.gov)

• Linus Pauling Institute at Oregon State University (http://lpi.oregonstate.edu/infocenter/)

• MedScape (www.medscape.com) – general clinical focus, continuing education, and helpful case studies

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Helpful resources: Subscription

• Pharmacist’s Letter/Prescriber’s Letter (www.pharmacistsletter.com or www.prescribersletter.com)

• Lexicomp (www.lexi.com) printed and electronic clinical tools• The Drug Information Handbook (annually updated) • Drug interactions checker

• Facts and Comparisons (www.factsandcomparisons.com) printed and electronic references

• Facts and Comparisons E Answers (with pill ID and interactions checker)

• ClinicalKey (https://www.clinicalkey.com) – clinically focused information; full-text references, full access articles, patient handouts

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