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
d
eficiency 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 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
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
i
nternalization
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).
Zimmermann MB, et al., Thyroid. 2002 Oct;12(10):867
-
78.
15
Source: http://upload.wikimedia.org/wikipedia/commons/8/82/Thyroid_hormone_synthesis.png
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
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
1.89
Source: Linus Pauling Institute:
http://lpi.oregonstate.edu
20
*3
-
oz serving of meat
is ~ size of
a deck of cards.
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 BID
1
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
Source: Facts & Comparisons
eAnswers
,
http://www.factsandcomparisons.com/facts
-
comparisons
-
online.aspx
34
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
2
10
7
6
6
5
5
4
4
3
15
10
9
9
8
7
7
6
5
20
16
15
14
13
12
11
10
9
25
20
18
17
16
15
14
13
12
30
23
22
21
19
18
17
15
14
35
27
26
24
23
21
20
18
17
40
31
29
28
26
24
22
21
19
45
35
33
31
29
27
25
23
21
50
39
37
35
32
30
28
26
24
55
43
41
38
36
33
31
28
26
60
47
44
42
39
36
34
31
28
65
51
48
45
42
39
36
34
31
70
55
52
49
45
42
39
36
33
75
59
55
52
49
45
42
39
35
80
63
59
55
52
48
45
41
38
85
66
63
59
55
51
48
44
40
90
70
66
62
58
54
50
46
42
95
74
70
66
62
57
53
49
45
100
78
74
69
65
60
56
52
47
105
82
77
73
68
63
59
54
50
110
86
81
76
71
67
62
57
52
115
90
85
80
75
70
64
59
54
120
94
88
83
78
73
67
62
57
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
r
eticuloendothelial
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
43
In summary,
i
ron 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
44
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
45
END
Questions?
46
Thanks!
Contact
information
Petra Eichelsdoerfer, ND, CN, RPh
petraelena@gmail.com
47
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
48
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
49
50
Enter the password to open this PDF file:
File name:
-
File size:
-
Title:
-
Author:
-
Subject:
-
Keywords:
-
Creation Date:
-
Modification Date:
-
Creator:
-
PDF Producer:
-
PDF Version:
-
Page Count:
-
Preparing document for printing…
0%
Comments 0
Log in to post a comment