Petra: Iron Deficiency and Environmental Exposures - New ...

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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