Transcript Iron Deficiency - New Hampshire Association of Naturopathic Doctors

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
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Who is at risk?
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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
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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
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
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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
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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 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
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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
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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
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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)
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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
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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).
Source: http://upload.wikimedia.org/wikipedia/commons/8/82/Thyroid_hormone_synthesis.png
Zimmermann MB, et al., Thyroid. 2002 Oct;12(10):867-78.
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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
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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
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Food sources of iron
• Heme iron (richest in highly perfused tissues)
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~ 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
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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
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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)
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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 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
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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 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
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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
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
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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
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
[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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