In this section
erythropoietin is widely used to maintain adequate haemoglobin
concentrations and avoid transfusion dependency in patients with
(Aranesp) is a novel
erythropoiesis stimulating protein produced by recombinant DNA
technology. It is produced in Chinese hamster ovary (CHO) cells by
recombinant DNA technology. Aranesp is a 165 amino acid protein
containing five N-linked oligosaccharide chains, whereas
erythropoietin contains only three. The additional carbohydrate
chains increase the molecular weight of the glycoprotein from
approximately 30,000 to 37,000 daltons. It has the advantage of
less frequent dosing.
(NeoRecormon) is a stable
recombinant human erythropoietin concentrate produced from
genetically engineered Chinese hamster ovary (CHO) cells containing
a cloned human erythropoietin gene.
The active ingredient, epoetin beta, is a
highly purified glycoprotein, identical in amino acid sequence to
endogenous erythropoietin, with an apparent molecular weight of
32,000 to 40,000 Daltons. Epoetin beta is
greater than or equal to 98% pure, with no detectable cell line
The Section 100 listing is for the treatment
of anaemia requiring transfusion associated with chronic renal
failure (Haemoglobin <100g/L).
The main cause of anaemia in children with
CRI is ineffective erythropoiesis caused by inadequate
erythropoietin production. Other causes include chronic
blood loss and increased RBC destruction caused by uraemia toxins
and / or dialysis. It is normocytic, normochromic
anaemia. The aim of management of renal anaemia
is for a target Hb of 120g/L in children over 1 year of age and
110g/L in children under 1 year of age.
First Evaluate causes of
Ensure Adequate Iron
Refer patient to Renal Anaemia Co-ordinator
(Ext 5721) and commence Epoetin Beta or Darbepoetin alfa if
If the increased in Hb is
inadequate (less than 10g/L in 4 weeks) and iron stores are
adequate, the dose of Epoetin Beta and Darbepoetin Alfa may be
increased by 25%. Further increases may be made at 4 week
intervals until the desired response is attained.
If the rise in Hb is
greater than 25g/L in 4 weeks, the dose of Epoetin Beta and
Darbepoetin Alfa should be decreased by 25-50%, depending on the
rate of increase. If the Hb exceeds 140g/L, doses should be
reinitiated at a dose approximately 25% below the previous
The cap needs to be removed from the syringe.
A needle must then be fixed on the syringe to allow injection. A
needle for subcutaneous administration is provided. Only solutions
which are clear or slightly opalescent, colourless and practically
free of visible particles may be injected. Epoetin Beta prefilled
syringes are sterile but do not contain preservatives. Product is
for single use in one patient only.
60 IU/kg/week administered Once weekly
Increase starting dose every 4 weeks by 60 IU/kg/week
if Hb increase is <5g/L
Adjust dose every 4-8 weeks to suit individual
120 IU/kg/week administered in 3 divided
Increase starting dose every 4 weeks by 240 IU/kg/week
if Hb increase is <5g/L
Darbepoetin Alfa can be administered SC or
IV. Chronic Renal Failure Dosage 0.45 mcg/kg SC or IV once weekly;
patients not on dialysis: 0.75 mcg/kg SC once every 2 weeks; adjust
dose as needed every 4 weeks to achieve rise in Hb of 10 to 25 g/4
wks; maintenance: aim for Hb of 110-140 g/L and adjust dose every
3-4 wks as needed.
Do not shake Darbepoetin alfa. Prolonged
vigorous shaking may denature any protein, rendering it
Parenteral drug products should be inspected
visually for particulate matter and discolouration prior to
administration. Do not use any products exhibiting particulate
matter or discolouration.
Do not dilute or administer Darbepoetin alfa
in conjunction with other drug solutions.
Darbepoetin alfa contains no antimicrobial
agent. Darbepoetin alfa is for single use in one patient only.
Discard any residue.
Allow the Darbepoetin alfa prefilled syringe
and prefilled pen to reach room temperature before
The Darbepoetin alfa prefilled pen
(SureClick) delivers the complete dose.
Darbepoetin alfa and Epoetin Beta are stable for up to 2 days at
During correction phase of
uraemic anaemia both Hb and Iron studies should be checked
monthly. During maintenance phase (i.e. following
attainment of target Hb), Hb should be checked monthly and iron
studies checked 3 monthly.
In patients with % sat >
50% +/or serum ferritin > 800µg/L, all iron supplements ahould
be withheld for up to 3 months at which time the iron studies
should be rechecked.
Iron is an essential
component of many protein molecules. Most of the body's iron
is consumed in the process of erythropoiesis. Iron bound to
the protein, transferrin, circulates in plasma and is taken up by
the developing RBC's in the bone marrow, where it forms one of the
main components of haemoglobin.
Absolute Iron deficiency is
when iron stores are inadequate to support bone marrow
requirements. Functional Iron deficiency is when iron stores
are adequate, but cannot supply quickly enough to satisfy
demand. The rate of release of iron from iron stores is
Measurement of Iron Stores
Measurements of iron stores
must be deferred for one week following an IV infusion of <200mg
Ferrum H, or for 2 weeks if larger doses are used.
This is a sensitive marker
for early iron deficiency. Hypochromic RBC's result
from low iron delivery to the bone marrow, causing some of the
RBC's to contain less than normal amounts of
Saturation of Transferrin
As iron is circulated on
the transferrin molecule, transferrin saturation is a measured of
Ferritin (measure of iron
Level should be >300µg/L
(target 300-650µ/L) in patients on erythropoietin
Serum Ferritin is not a
specific marker of iron status, as it is an acute phase
reactant. As such, it can increase in the setting of
Other measurements that can
be used are:
Little use in isolation.
Diurnal variation in
concentration marked (low in early afternoon)
b) Red Blood
Volume (<77 fl)
Haemoglobin content (<25 pg)
c) Distribution of
>15% variation (elevated by increased
due to EPO treatment, older
cells get smaller in renal failure)
transferrin receptor increased in iron deficiency normal in chronic
Supplementary iron should
be administered to prevent iron deficiency and to maintain adequate
iron stores, so that the target Hb can be achieved.
Most children receiving
Darbepoetin Alfa or Epoetin Beta will require iron supplementation,
as sustained erythropoiesis mobilizes and eventually exhausts iron
stores if adequate supplementation is not administered.
If oral iron is given it
should be given as a daily dose of 2-3mg/kg, and is best absorbed
without food or other medications.
Intravenous Iron - Dosage
IV iron is more efficacious
than oral iron for correction of uraemic anaemia with Darbepoetin
Alfa or Epoetin Beta.
IV iron can be
Contraindications for IV Iron
Iron tends to accumulate in
inflamed tissues; therefore it should not be given intravenously to
patients with severe inflammation or infection of the kidney or
Ferrum H should not be given to
patients presenting with any of the following
As elemental iron tends to accumulate in
inflamed tissues, parenteral iron should not be given to patients
with severe inflammation or infection of the kidney or
Adverse Reactions to IV Iron
Adverse reactions to parenteral Ferrum H have
only been reported infrequently. However the following reactions
are known to have occurred after parenteral iron
General. Flushing, sweating, chills and fever;
chest and back pain.
Gastrointestinal. Nausea and
Musculoskeletal. Joint and muscle
pain; arthralgia; sensation of stiffening of the arms, legs or
Cardiovascular. Faintness; syncope; tachycardia; hypotension;
Respiratory. Bronchospasm with dyspnoea.
Haematological. Generalised lymphadenopathy.
Dermatological. Rash; urticaria;
Adverse reactions may be delayed by one to
two days after treatment with Ferrum H injection.
IV Iron Infusion low-dose course for children on
For children undergoing HD,
incremental IV iron infusion can be given at a dose of Ferrum H
2mg/kg weekly (up to a maximum of 100mg)
A test dose of IV iron
should be given prior to first dose.
Administration of Iron on
Ferrum H is given diluted
into 20mls of Normal Saline over 1 hour during the last hour of
Iron levels should be
checked one week after iron infusion. The test should be done
after haemodialysis from the venous line.
During low-dose course of
Ferrum H, the Hb and iron studies should be rechecked every 8
Test Dose of IV Iron
An initial test dose of
iron polymaltose should be given prior to the first therapeutic
dose of the drug. Adrenaline and facilities for cardiopulmonary
resuscitation must be available. In the case of a mild allergic
reaction, administer antihistamines.
Dose for test-
The test-dose should be
given during the day-time and medical staff must be present
during administration and for 15 minutes following
Vital signs should be
monitored 15 minutely and observe child closely for 30 minutes for
The test-dose should be
given by slow IV push over 30-60 seconds. The remainder of
the iron dose should not be given until at least 1 hour after
test-dose has been given. If no immediate allergic reactions
occur, subsequent routine dosing can be given without a