Iron therapy

Iron therapy

Iron is stored only in ferric form, in combination with a large protein apoferritin
most important storage sites are reticuloendothelial (RE) cells
Daily requirement

absorption occurs all over the intestine, but majority in the upper part

Factors facilitating iron absorption

Acid:
by favouring dissolution and reduction of ferric iron.
Reducing substances: ascorbic acid, amino acids containing SH radical. These agents reduce ferric iron and form absorbable complexes.
Meat: by increasing HCI secretion and providing haeme iron.

Factors impeding iron absorption

Oral iron

preferred route of iron administration
Dissociable ferrous salts are inexpensive, have high iron content and are better absorbed than ferric salts, especially at higher doses.
Gastric irritation and constipation (the most important side effects of oral iron) are related to the total quantity of elemental iron administered.
Some simple oral preparations are:
Ferrous sulfate: (hydrated salt 20% iron, dried salt 32% iron) is the cheapest; may be preferred on this account. It often leaves a metallic taste in mouth
Ferrous gluconate ( 12% iron)
Ferrous fumarate (33% iron):
Colloidal ferric hydroxide (50% iron)
A total of 200 mg elemental iron (infants and children 3- 5 mg/kg) given daily in 3 divided doses produces the maximal haemopoietic response.
Prophylactic dose is 30 mg iron daily.
S/E à Epigastric pain, heartburn, nausea, vomiting, bloating. staining of teeth, metallic taste, colic, etc. are the frequent complaints.
Tolerance to oral iron can be improved by initiating therapy at low dose and gradually escalating to the optimum dose.
Constipation is more common

Parenteral iron

Iron therapy by injection is indicated only when:

Oral iron is not tolerated: bowel upset is too much.
Failure to absorb oral iron: malabsorption: inflammatory bowel disease.
Chronic inflammation (e.g. rheumatoid arthritis) decreases iron absorption, as well as the rate at which iron can be utilized.
Non-compliance to oral iron.
In presence of severe deficiency with chronic bleeding.
Along with erythropoietin in chronic kidney disease (CKD) patients: oral ion may not be absorbed at sufficient rate to meet the demands of induced rapid erythropoiesis.

The ionized salts of iron used orally cannot be injected because they have strong protein precipitating action and free iron in plasma is highly toxic.

lron-dextran

high molecular weight colloidal solution containing 50 mg elemental iron/ml.
only preparation that can be injected i.m. as well as i.v.
By i.m. route it is absorbed through lymphatics, circulates without binding to transferrin and is engulfed by RE cells where iron dissociates and is made available for haeme synthesis.
In the injected muscle 10- 30% of the dose remains locally bound and becomes unavailable for utilization for several weeks.
Thus, 25% extra needs to be added to the calculated dose.
Because dextran is antigenic, anaphylactic reactions are more common than with the newer preparations.
Intramuscular: Injection is given deeply in the gluteal region using Z track technique (to avoid staining of the skin).
Intravenous: A dose of 2 ml containing 100 mg iron is injected per day taking 10 min for the injection.
Alternatively, the total calculated dose is diluted in 500 ml of glucose/saline solution and infused i.v. over 6-8 hours under constant observation.
Injection should be terminated if the patient complains of giddiness, paresthesias or tightness in the chest.

Adverse effects
local Pain at site of i.m. injection, pigmentation of skin. sterile abscess- especially in old and debilitated patient.
Systemic à Fever, headache, joint pains, flushing, palpitation, chest pain, dyspnoea, lymph node enlargement are more common than with the newer formulations.
An anaphylactoid reaction

Ferrous-sucrose

high molecular weight complex of iron hydroxide with sucrose, that on i.v. injection is taken up by RE cells, where iron dissociates and is utilized.
safer than the older iron dextran and a dose of 100 mg (max 200 mg) can be injected i.v. taking 5 min, once daily to once weekly till the total calculated dose ( including that to replenish stores) is administered.
However, total dose i.v. infusion is not possible.
solution is highly alkaline ruling out i.m./s.c. injection.
The incidence of hypersensitivity reaction is very low.
This preparation is particularly indicated for anaemia in kidney disease patients.
Oral iron should not be given concurrently and till 5 days after the last injection.

Ferric carboxymaltose

ferric hydroxide core is stabilized by a carbohydrate shell.
The macromolecule is rapidly taken up by the RE cells, primarily in bone marrow (upto 80%), as well as in Iiver and spleen.
Administered either as daily 100 mg i.v. injection, or upto 1000 mg is diluted with I00 ml saline (not glucose solution) and in fused i. v. taking 15 min or more.
should not be injected i.m à clinical trials, it has caused a rapid increase in haemoglobin level in anaemia patients and replenished stores.
Pain at injection site. And rashes have occurred, but anaphylaxis is rare.
Not recommended for children < 14 years.

Iron isomaltoside-1000

Latest injectable iron formulation for i.v. use marketed in India in 2016.
consists of iron bound tightly in a matrix of isomaltosie-1000, which is an oligosaccharide with mean M.W. o f 1000.
After i.v. injection, iron isomaltoside is rapidly taken up into the RE cells and then slowly released for use by the erythropoietic cells.
The tight binding within the matrix releases very little labile iron which is responsible for toxicity.
This permits administration of high single dose of 1- 2 g (upto 20 mg/kg) i.v. over 15- 30 min.
Thus, full iron deficit can be corrected by a single short-period i.v. infusion, which is not only more convenient and cost saving, but also avoids multiple exposure of the patient to i.v. iron.
Alternatively I00-200 mg i.v. may be injected over 5 min daily.
Efficacy of iron isomaltoside comparable to iron dextran or iron sucrose
the immunogenic potential of iron isomaltoside-1000 is low
It may be concluded that currently ferric carboxymaltose and iron isomaltoside-1000 are the two most convenient and safest i.v. iron formulations.

Use

Iron deficiency anaemia

Most important indication for medicinal iron.
The RBCs are microcytic and hypochromic
Apart from nutritional deficiency, chronic bleeding from g.i. tract {ulcers, inflammatory bowel disease, hookworm infestation) is a common cause.
Iron should be normally administered orally; parenteral therapy is to be reserved for special circumstances
rise in Hb level by 0.5- 1 g/dl per week is an optimum response to iron therapy.
therapy should be continued till normal Hb level is attained (generally takes 1- 3 months depending on the severity of anemia) and 2- 3 months or more thereafter to replenish the stores.

Prophylaxis:

The amount of iron available from average diet – 3 mg/day.
Later half of pregnancy and infancy are periods when iron deficiency will develop unless medicinal iron is supplemented.