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ORAL AND PARENTERAL

IRON PREPARATIONS

Arun George
OG 4

Iron needs in Pregnancy


Fetus

and placenta 300mg


Red cell expansion - 500mg
Loss in sweat, urine- 200mg
Blood loss at delivery 200mg
Total

need = 1200mg
Iron saved due to amenorrhoea = 300mg
Net need in pregnancy = 900mg
Mukherji J. Iron deficiency anemia in pregnancy. Rational Drug
Bull. 2002;12:25

Why iron supplementation


?
Iron

- used during the later half of pregnancy.

the

iron requirement increases from a 0.8 mg/day in


the first trimester to 6 to 7 mg/day in the second half
of pregnancy.

Avg

- 2 to 4.8 mg of iron per day

amount

of iron absorbed from diet - insufficient to


meet the demands imposed by pregnancy.

Therefore,

iron supplementation during pregnancy is


recommended universally even in non anemic women.

IRON SUPPLEMENTS

Oral preparations

Therapeutic oral iron


preparations
Preparations of iron salt
Ferroussulfate
Ferrousfumarate
Ferrousgluconate
Ferrousglycine sulfate
Ferroussuccinate
Ferrouscalcium citrate
Ferrousamoniate
Ferric ammonium citrate
Ferrousascorbate

API, 2008

Others
Iron polysaccharide
complex
(iron
polymaltose)
Carbonyl iron
Sodium
feredetate
Combination of iron
salts & Vit C,
succinate, fructose
Haemoglobin
preparations

Oral
Prophylaxis:

Iron supplementation
100mg elemental iron
500mcg folic acid
for 100 days
(national anemia control program)

Standard therapy

for

iron-deficiency anemia in adults is a 300-mg tablet


of ferrous sulphate (60 mg of iron) 3 times per day.

Although

absorption is enhanced when given on an


empty stomach, nausea and epigastric pain sometimes
results.

Iron

supplementation during pregnancy is advisable in


developing countries, where women often enter
pregnancy with low iron stores.
-Cook JD. Diagnosis and management of iron deficiency anaemia. Best Pract Res Clin Haematol. 2005;18:319
332
-WHO guidelines

General principles
Iron is not absorbed in the stomach and is absorbed
best from the duodenum and proximal jejunum, where
the iron transport proteins (eg, duodenal iron
transporter, divalent metal transport protein and the
iron export protein to blood, ferroportin) are most
strongly expressed.
Iron salts should not be given with food because
phosphates, phytates, and tannates in food bind the
iron and impair its absorption.
A number of other factors can inhibit the absorption of
iron salts, including antacids, H receptor blockers,
proton pump inhibitors, calcium-containing foods and
beverages, calcium supplements, certain antibiotics
(eg, quinolones, tetracycline), and the ingestion of iron
along with cereals, dietary fiber, tea, coffee, eggs, or

Iron

is best absorbed as the ferrous (Fe ) salt in a


mildly acidic medium. As a result, we usually add
a 250 mg ascorbic acid tablet or a half-glass of
orange juice at the time of iron administration to
enhance the degree of iron absorption.

The

iron preparation used should be based upon


cost and effectiveness with minimal side effects.

The

least expensive preparation is ferrous


sulfate; each tablet contains 325 mg of iron salts,
of which 65 mg is elemental iron.

Gastrointestinal

tract symptoms (eg, abdominal


discomfort, nausea/vomiting, diarrhea/constipation)
suffered by some patients seem to be directly related
to the amount of elemental iron ingested.

Thus,

the reported low incidence of side effects for


some preparations can be explained by their low
elemental iron content.

Patients

with persistent gastric intolerance to oral


iron tablets may tolerate ferrous sulfate elixir, which
provides 44 mg of elemental iron per 5 mL. Patients
can titrate the dose up or down to the level at which
the gastrointestinal symptoms become acceptable.

Response
Hemoglobin

increases at a rate of
0.1g/dL/day starting from the
second week of treatment.
Reticulocytosis
feeling of well being, appetite
No significant improvement in 3
weeks further evaluation

Reasons for failure of Rx


Various

malabsorptive states (eg, celiac disease, Whipple's disease,


bacterial overgrowth syndromes)

In

patients with inflammatory bowel disease, the use of oral iron has been
associated with worsening of the underlying disease, and may be poorly
tolerated and ineffective

inability

to absorb oral iron (eg, impaired iron transport, concomitant use


of calcium-containing salts, H blockers, phosphate binders, generalized
malabsorption).

Gastrointestinal

side effects - poor adherence to therapy.

Inflammation-mediated

induction of hepcidin, which regulates iron


homeostasis, may result in suboptimal gastrointestinal absorption of
orally administered iron in iron deficient subjects.

Non-response

to oral iron therapy does not rule out iron deficiency in such
subjects, since two-thirds of the non-responders to oral iron in one study
responded to treatment with intravenous iron (ferric carboxymaltose).

NEW THERAPEUTIC ALTERNATIVES

CARBONYL Iron
Iron ascorbate
ADVANTAGES
a) Outstanding GI Tolerance
b) Very safe with no poisoning even
in high doses
c) No interaction with food stuffs
d) Delicious with non-metallic taste
and dont stain the patients
teeth
e) Compliance is very high

PARENTERAL
IRON

Indications for parenteral iron therapy


Intolerant

or unresponsive to oral

Iron
Necessity for faster increase in
haemoglobin (Elective surgery)
Malabsorption syndromes
Avoidance of allogenic blood
transfusion
Moderate to severe anemia around
30 weeks in pregnancy(ICMR)

When Should Parenteral Iron be


Used in Pregnant Patients?
In

most clinical circumstances, oral preparations are appropriate and


sufficient.

Guideline for Giving Parenteral Iron Sucrose


Hb<8g%iron.
14Day oral dose failure.
No haemoglobinopathy.
Parental Iron
High molecular weight, iron dextrose is NOT recommended for use.
Newer preparations like iron sucrose are effective and safe with
minimal adverse reactions.
In comparison with patients who take iron dextran, patients who take
ferrous sucrose have fewer allergic reactions (8.7 vs. 3.3 allergic
events per 1,000,000 doses) and a significantly lower fatality rate
(31 vs. 0,P<0.001), hence it is the preferred molecule of choice.
Iron sucrose molecule used should have 30,00060,000molwt.
Good Clinical Practice Recommendations for Iron Deficiency Anemia in Pregnancy (IDA) in
Pregnancy in India
J Obstet Gynaecol India. Oct 2011; 61(5): 569571.

Parental

Iron
High molecular weight, iron dextrose is NOT
recommended for use.
Newer preparations like iron sucrose are effective
and safe with minimal adverse reactions.
In comparison with patients who take iron
dextran, patients who take ferrous sucrose have
fewer allergic reactions (8.7 vs. 3.3 allergic
events per 1,000,000 doses) and a significantly
lower fatality rate (31 vs. 0,P<0.001), hence it
is the preferred molecule of choice.
Iron sucrose molecule used should have 30,000
60,000molwt.

Parenteral iron
Elemental

Fe Requirement (mg)

=
(N Hb Pt. Hb) X Wt(kg) x 2.21
+ 1000

Dosage and Technique of


Administration
Fesucrose

administered as either a
bolus (undiluted) over 510min on
outpatient basis or short infusion less
than 30min (in 200ml Nacl (9g/l)).

Maximum

cumulative doses 1,600mg in


pregnancy (200mg twice per week to a
target Hb of 11.0g/l or for a maximum
of 4weeks), Mean treatment duration
21days (829days).

Pre-requisites for parenteral


therapy

Should be given under proper supervision


After test dose only
Close monitoring required
Inj. Adrenaline, Hydrocortisone and oxygen
to be available for management of
anaphylactic reactions.
Cardiopulmonary resuscitation facility to be
available.
Other indications for parenteral iron therapy
are poor compliance or intolerance to oral
iron therapy.

Parenteral preparations:
Intravenous preparation
a) Iron dextran (Imferon)
b) Iron sucrose
c) Sodium ferric gluconate (ferrlecit)

Intramuscular preparation
d) Iron Sorbitol Citrate in dextrin (Jectofer)
e) Iron Dextran (imferon)

Iron dextran: 50 mg/mL. Iron sucrose: 20 mg/mL.


Ferric gluconate: 12.5 mg/mL

IM ROUTE
Iron Dextran (1ml contains 50mg elemental
iron & 1amp=2ml)
Dose : 100 mg IM OD till the total dose over
Drawbacks:
a) Painful injection (less with jactofer).
b) Skin discoloration
c) Local abscess
d) Allergic reaction
e) Fe over load.
f) Category C drug
g) Gluteal sarcoma
h) Test dose needed

Advantage
Can be given in primary care set up
Absolute reticulocyte count increases in 7 days
Hemoglobin increases within 1-2 wks
Whole dose can be given in single setting

I/V Route :
a) Repeated Injections
b)Total dose infusion
Side effects:
- Anaphylactic reaction.
- Chest pain, rigors, chills, fall in
BP, dyspnoea, hemolysis.
Treatment:
a) Stop infusion.
b) Give antihistaminics,
corticosteroids & epinephrine.

IRON DEXTRAN
a) Colloidal solution of ferric
oxyhydroxide complexed with
polymersised dextran
b) Advantage : patients total iron
requirement is given in one
administration
c) Higher rate of adverse effects
like delayed hypotension/
arthralgia/abdominal pain
d) Test dose is necessary
e) Patients should be monitored 1
hr following a test dose of 25 mg

FERRIC GLUCONATE COMPLEX IN


SUCROSE
1)

Given as IV injection/infusion

2)

Standard dose of 125 mg may


be given IV injection over 10
min

3)

Rate should be < 12.5mg/min

4)

Dose can be repeated if


ferritin < 100ng/ml or
saturation < 20%

IRON SUCROSE
Commonly

used in chronic kidney

diseases
MW 34,000-60,000 D
Iron hydroxide sucrose complex in
water
Given as IV injection/infusion
Each ml contains 20 mg of Fe
After IV administration it
dissociates into iron & sucrose
T 1/2 is 6hrs
Category B drug

Total

iron deficit = Body weight x


(Target Hb Actual Hb) x 2.4 + Iron
stores [mg]

Administered

100 mg IV over 5
thrice
weekly until

minutes,
1000 mg
200mg max dose per Sitting
Rate of administration should not
more than 20 mg/min
Infusion : 50 mg to be injected
slowly over 2 minutes, wait for 23 min ,then give another 50 mg

Advantages of IRON SUCROSE over


others
a) All iron preparations were capable of
causing tissue peroxidation except iron
sucrose
b)Less oxidative injury
c) Less risk of tissue parenchymal injury by
free iron.
d)Higher availability for erythropoiesis
than iron Dextran
e) IV iron supplementation increases the
erythropoiesis 5 times
f) Safe in dextran sensitive patients
g)Minimal side effects

The Hb rise will be evident in as


early as 5 days
IV iron sucrose is safe &
effective
Iron sucrose is given both bolus
push & infusion
Disadvantage
a) Total dose administered in
multiple infusions
b)Needs
a set up where
anaphylactic reaction can be

NEWEST FAST ACTING IV


MOLECULES
III
Carboxymaltose

Iron
(FERRINJECT) :
a) Ferric
hydroxide
carbohydrate complex which
allows for control delivery of
iron within cells of the RES
(primarily bone marrow) and
subsequently delivery to the
iron binding proteins ferritin
and transferin
b)T1/2 : 16 hr

IRON III ISOMALTOSE(MONOFER)


a) Strongly
bound
iron
in
spheroid
iron-carbohydrate
particle providing slow release
of bioavailale iron to iron
binding proteins
b)Rapidly up taken by RES and
little risk of free iron for tissue
damage
c) Dose : 1000 mg in a single
infusion

FERUMOXYTOL

USA FDA approved this drug


in 2009 for iron replacement
in patients with IDA & CKD

No test dose required

Can be given as large dose


(510 mg/vial) in <20
Seconds in single settings

No significant side effects

Not approved in Europe

ORAL Vs IV
Intravenous

iron treated iron-deficiency


anemia of pregnancy and restored iron
stores faster and more effectively than oral
iron, with no serious adverse reactions.

Intravenous Versus Oral Iron for Treatment of Anemia in Pregnancy


A Randomized Trial
Ragip A. Al, MD, Eylem Unlubilgin, MD, Omer Kandemir, MD, Serdar Yalvac, MD, Leyla Cakir, MD,
and Ali Haberal, MD
(Obstet Gynecol 2005;106:133540)

Management of anaemia
on the basis of
haemoglobin levels
among pregnant and
lactating women
UNICEF INDIA National Iron Plus initiative Guidelines for
Control of IDA

Hb level between 911 gm/dl

2 IFA tablets (1 in the morning and 1 in the


evening) per day for at least 100 days (at
least 200 tablets of IFA).
Hb levels should preferably be reassessed
at monthly
intervals. If on testing, Hb has come up to
normal level,
discontinue the treatment.

Hb level between 89 gm/dl


Before

starting the treatment, the


woman should be investigated to
detect the cause of anaemia.
Oral IFA supplementation as for Hb
level 911 gm/dl.
Hb testing to be done every month.
Depending on the response to
treatment, same course of action as
prescribed for Hb level between 911
gm/dl.

Hb level between 78 gm/dl


Before

starting the treatment, the woman should be


investigated to diagnose the cause of anaemia.

Injectable

IM iron preparations (parenteral iron) should be


given if iron deficiency is found to be the cause of
anaemia.

IM

iron therapy in divided doses along with oral folic acid


daily if women do not have any obstetric or systemic
complication; repeat Hb after 8 weeks.

If

the woman has become non-anaemic, no further


medication is required:
if Hb level is between 911 gm/dl, same regimen of oral
IFA prescribed for this range.

Multiple dose regime


Intramuscular

(IM) - Test dose of 0.5


ml given deep IM and woman
observed for 1 hour.
Iron dextran or iron sorbitol citrate
complex given as 100 mg (2 ml)
deep IM in gluteal region daily.
Recommended dose is 15002000
mg (IM in divided doses) depending
upon the body weight and Hb level

Hb level between 5-7 gm/dl


Continue

parenteral iron therapy as for Hb


level between 78 gm/dl. Hb testing to be
done after 8 weeks

If

the woman becomes non-anaemic, no


further medication is required: if Hb level is
between 911 gm/dl, same regimen of oral
IFA prescribed for this range

Depending

on the further response to


treatment, same course of action as
prescribed for Hb level between 911 gm/dl

Hb level less than 5 gm/dl

Evidence for injectable IV sucrose


preparation: under
Randomised Control Trial of GOI
Immediate hospitalisation irrespective
of period of
gestation in hospitals where round-theclock specialist
care is available for intensive
personalised care and decision for blood
transfusion (packed cell transfusion)

Thank you

Romans 8:28
And we know that for those who love God all things work together
for good, for those who are called according to his purpose.