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
1
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
2
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
3
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
4
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
5
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
6
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 irondependent enzymes
• Microcytic, hypochromic RBCs
• Elevated HbA1C
Linus Pauling Institute, http://lpi.oregonstate.edu
Beard J L J. Nutr. 2001;131:568S-580S
©2001 by American Society for Nutrition
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 esophagus
Source: Linus Pauling Institute, http://lpi.oregonstate.edu
8
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
9
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
10
Intestinal absorption of heme iron
Heme 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
11
Regulation of intestinal iron uptake
Heme 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
12
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
13
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 state
Dhur, et.al., J Nutr 119: 40 - 47, 1989
14
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).
Source: http://upload.wikimedia.org/wikipedia/commons/8/82/Thyroid_hormone_synthesis.png
Zimmermann MB, et al., Thyroid. 2002 Oct;12(10):867-78.
15
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
16
Iron Deficiency: Treatment
• Dietary changes to enhance iron absorption
• Botanical, nutritional, and nutraceutical supplements useful for iron
deficiency
• Parenteral iron products
17
Iron: Recommended Dietary Allowance
Life 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
Source: Linus Pauling Institute, http://lpi.oregonstate.edu
18
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 – 588
Linus Pauling Institute, http://lpi.oregonstate.edu
19
Iron content of foods
Food
Serving
Beef
Chicken, dark meat
Oysters
Shrimp
Tuna, light
Black-strap molasses
Raisin bran cereal
Raisins, seedless
Prune juice
Prunes (dried plums)
Potato, with skin
Kidney beans
Lentils
Tofu, firm
Cashew nuts
3 ounces*, cooked
3 ounces, cooked
6 medium
8 large, cooked
3 ounces, canned
1 tablespoon
1 cup, dry
1 small box (1.5 ounces)
6 fluid ounces
~ 5 prunes (1.7 ounces)
1 medium potato, baked
1/2 cup, cooked
1/2 cup, cooked
1/4 block (~1/3 cup)
1 ounce
*3-oz serving of meat is ~ size of a deck of cards.
Iron content (mg)
2.32
1.13
5.04
1.36
1.30
3.50
5.79-18.00
0.81
2.28
0.45
1.87
1.97
3.30
2.15
1.89
Source: Linus Pauling Institute: http://lpi.oregonstate.edu
20
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]
21
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
22
Nutrient Interactions
Vitamin 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 meal
Source: Linus Pauling Institute: http://lpi.oregonstate.edu
23
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
24
Supplementing Iron: Adverse effects
• Directly correlated with unabsorbed iron content
• Nausea, vomiting
• Intestinal cramping, bloating, gas
• Constipation, diarrhea
25
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
26
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
27
Non-heme iron supplements
Common 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
28
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
29
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
30
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
31
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
32
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
33
Table for estimating total iron dextran required for restoring Hb & Iron Stores
Patient
LBW (Kg)
5
10
15
20
25
30
35
40
45
50
55
60
65
70
75
80
85
mL requirement of iron dextran injection based on observed hemoglobin of:
3 g/dL
4 g/dL
5 g/dL
6 g/dL
7 g/dL
8 g/dL
9 g/dL
10 g/dL
3
3
3
3
2
2
2
2
7
6
6
5
5
4
4
3
10
9
9
8
7
7
6
5
16
15
14
13
12
11
10
9
20
18
17
16
15
14
13
12
23
22
21
19
18
17
15
14
27
26
24
23
21
20
18
17
31
29
28
26
24
22
21
19
35
33
31
29
27
25
23
21
39
37
35
32
30
28
26
24
43
41
38
36
33
31
28
26
47
44
42
39
36
34
31
28
51
48
45
42
39
36
34
31
55
52
49
45
42
39
36
33
59
55
52
49
45
42
39
35
63
59
55
52
48
45
41
38
66Facts & Comparisons
63
59 http://www.factsandcomparisons.com/facts-comparisons-online.aspx
55
51
48
44
40
Source:
eAnswers,
34
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
35
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/dose
Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx
36
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
37
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 hours
Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx
38
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
39
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 minutes
Source: Facts & Comparisons eAnswers, http://www.factsandcomparisons.com/facts-comparisons-online.aspx
40
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
41
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
42
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, RPh
petraelena@gmail.com
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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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