1. sports
2. curling

medication review
The articles in this series are independently researched and compiled by PSA commissioned authors and peer reviewed.
Iron deficiency anaemia
Continuing Professional Development
By Katie Hayes
Case details
Jennifer is a 36-year-old regular
customer of the pharmacy, who lives
with her husband and two children.
She has a past medical history
which includes depression, anxiety,
gastro-oesophageal reflux disease,
endometriosis, asthma, migraine
and a shoulder injury. Jennifer had a
hysterectomy about six months ago
and has undergone several surgical
procedures since, for infection at
the site of hysterectomy. She is
also scheduled to have surgery on
her shoulder to repair a suspected
torn cartilage.
Learning objectives
After reading this article you should
be able to:
Jennifer’s current medications are:
• esomeprazole 40 mg, one
tablet daily
• diclofenac 50 mg, one tablet daily
• Identify signs and symptoms of
iron deficiency anaemia
• Describe the pharmacological
management options in iron
deficiency anaemia
• Identify possible adverse effects
of iron administration.
Competency standards (2010)
addressed:
7.1.1, 7.1.2, 7.1.3, 7.1.4
• paracetamol 500 mg/codeine 30 mg,
two tablets taken three times daily
Accreditation number:
CAP110606g
• Metamucil capsules, one capsule
daily
• oxycodone 5 mg, one tablet twice
daily when required (infrequent use)
• salbutamol 100 mcg MDI, one
puff to be taken occasionally
when required
• zolpidem CR 12.5 mg, one tablet
at night when required (uses about
twice a week)
• senna 7.5 mg, two tablets daily
Vol. 30 – June #06
• multivitamin tablet, one tablet on
alternate days
Katie Hayes is a consultant pharmacist
and manager of Risdon Vale Pharmacy in
Tasmania. She is currently studying for a
Master of Clinical Pharmacy through UTAS.
500
Jennifer is currently suffering
from constipation due to her
medications, her diet, lack of
exercise, and her recent surgical
procedures. She currently has iron
deficiency anaemia, as indicated by
her laboratory results (see Table 1).
She is not taking iron tablets at
present, as they may worsen her
narcotic-induced constipation.
Jennifer complains of feeling tired
and lethargic and lacks appetite;
she is noticeably pale and looks
visibly thinner than usual. She has
noticed hair loss recently; and
although she describes being in a
low in mood, she states that she
doesn’t want to take medication for
this at present.
Iron deficiency anaemia
Iron deficiency is a common cause of
anaemia in Australia.1 It is caused by
inadequate iron intake, inadequate iron
absorption and/or excessive iron loss.2
Iron is required for the production of
haemoglobin and myoglobin, and the
clinical consequences of deficiency
tend to be a result of the reduced
levels of these two proteins.
Diagnosis
Early in deficiency, patients generally
have mild signs and symptoms such
as fatigue or lethargy.3 As deficiency
Submit your answers online at www.psa.org.au and receive automatic feedback
Table 1. Blood test results for Jennifer
Pathology test
Result
Reference range
haemoglobin (Hb)
105 g/L
adult female: 115–165 g/L
haematocrit (Hct)
0.31
adult female: 0.37–0.47
mean cell volume (MCV)
79 fL
platelet count
147 x 10 /L
150–400 x 109/L
red cell count (RCC)
3.6 x 10 /L
adult female: 3.8–5.8 x 1012/L
white cell count (WCC)
7.3 x 109/L
4–11 x 109/L
iron
9 micromol/L
10–30 micromol/L
transferrin
3.1 g/L
1.7–3.0 g/L
ferritin
14 microgram/L
15–200 microgram/L
80–100 fL
9
12
Blood test results that may indicate
iron deficiency anaemia include: low
haemoglobin, low mean corpuscular
volume, low ferritin, high transferrin,
high total iron binding capacity
(TIBC), low transferrin saturation.3,6
Transferrin is a globulin protein
that binds iron in the plasma and
transports it to the bone marrow
in readiness for red blood cell
production.6 Ferritin is the major ironstorage protein and is indicative of
total body iron stores – this tends
to be reduced in iron deficiency
anaemia.6 Ferritin levels tends to
reduce before other laboratory
indicators of iron deficiency and is
the most reliable indicator of iron
deficiency anaemia.6,7 TIBC indicates
the quantity of proteins which are
available for binding mobile iron and
these are usually elevated in iron
deficiency anaemia.6
Treatment
It is important to establish the
cause of the iron deficiency anaemia
because treatment may not be
successful or the anaemia may
return if the cause is not corrected.1
Common causes are inadequate
dietary iron intake, problems with
absorption or more serious causes
such as gastrointestinal bleeding.1 The
treatment of iron deficiency anaemia
depends largely on severity at time of
diagnosis.
Oral iron supplementation
A mild iron deficiency anaemia,
which is identified through laboratory
results because few symptoms are
evident, can be treated with oral iron
supplementation.8,9 The recommended
dose for iron supplementation is
100–200 mg of elemental iron daily.8,9
Correct administration of oral iron
replacement is important to increase
its effectiveness and where possible
should be taken on an empty stomach
to maximise absorption.9 However,
many individuals experience sideeffects such as abdominal pain,
Table 2. Signs and symptoms of iron deficiency anaemia2–5
tired, listless, lifeless
Skin
pale, inelastic, dry
Hair
thinning
Mouth/
gastrointestinal
tract
glossitis, oesophageal webbing, angular stomatitis, gastric atrophy,
angular cheilitis, tongue erythema
Eyes
white or pale blue sclerae
Nails
brittle, concave (koilonychia), flattened
Cardiovascular
tachycardia, slight cardiomegaly
Oral intake
pica: unusual craving for substances with no nutritional value
including (e.g. clay, paper, ice, paint, starch)
Spleen
splenomegaly in severe, untreated disease
Patients who cannot tolerate oral iron
therapy or who have more severe
iron deficiency, can be administered
parenteral iron.8,9 In Australia, there
are two preparations of parenteral iron
available: iron polymaltose complex
(also known as iron dextrin) and iron
sucrose.8,9,11,12
Whenever parental iron is required,
intravenous (IV) administration is
recommended over intramuscular
(IM) administration due to poor
iron absorption, injection site pain
and skin discolouration from IM
administration.8,12 In the general
practice clinic however, IM iron
administration is practical and the
use of correct injection technique will
minimise these adverse effects.8,13
Adverse reactions that are associated
with parenteral iron administration
include nausea, vomiting, headache,
hypotension, hypertension,
tachycardia, bradycardia, fever, chest
pain, rash and angioedema.4,9
Reported adverse reactions to
different iron complexes used
internationally include: iron dextran
50%, iron sucrose 36% and ferric
gluconate 35%.4 Intravenous iron
sucrose has a lower risk of adverse
effects than IV iron polymaltose.8
Iron dextran has been associated
with anaphylaxis in 0.6–0.7% of
patients, 0.002% in patients who
are administered iron sucrose and
0.05% in patients administered with
ferric gluconate with the frequency of
serious or life-threatening reactions
caused by ferric gluconate and
iron sucrose considered rare.4,14
501
Vol. 30 – June #06
Appearance
Injectable iron supplementation
Continuing Professional Development
progresses, the symptoms usually
become more severe and serious and
may include chest pain and shortness
of breath.2–5 The general signs and
symptoms of iron deficiency anaemia
are listed in Table 2.
nausea, vomiting, constipation and/
or diarrhoea – in this situation iron
supplements can be taken with food
to enhance compliance, albeit with
reduced iron absorption expected.8,9
Oral iron supplements may bind
with some medications and reduce
both their activity (e.g. tetracyclines
and quinolones) and the amount of
iron absorbed.10 Some medications
may decrease the activity of iron
e.g. calcium supplements and
antacids.9,10 Other medications,
for example, thyroid hormones,
bisphosphonates, methyldopa and
levodopa have their activity reduced by
the concurrent administration of oral
iron supplements.10 Iron supplements
should be spaced several hours away
from all these medications so that the
efficacy of both is retained.9,11
medication review
Continuing Professional Development
The articles in this series are independently researched and compiled by PSA commissioned authors and peer reviewed.
The cause of the anaphylaxis with
iron dextran is thought by some to
be attributed to the dextran moiety
as opposed to iron itself.4 There is
some evidence however, that toxicity
rather than anaphylaxis may cause
adverse reactions due to a greater
number of reactions occurring with
an increase in the dose and infusion
rate, but some of adverse effects
indicate allergy-related mechanisms
and include; bronchospasm,
angioedema and urticarial and both
mechanisms should be considered
when assessing a patient experiencing
adverse effects.15 There has been a
significant reduction in the rate of
adverse reactions, particularly serious
reactions, since the administration of
iron polymaltose largely replaced that
of iron dextran.7 One audit examining
401 infusions in 386 patients found
that there were no incidences of
anaphylaxis or cardiorespiratory issues
in patients administered total dose
iron polymaltose infusions, and the
side-effects that were experienced
were mild and infrequent.16,17 A quality
assurance project conducted in a
primary care clinic in Sydney with
43 adult patients given a total or 89 IV
iron polymaltose injections found that
no serious reactions occurred.7 Similar
findings have since been reported
in other trials.18 While intravenous
iron sucrose is associated with
fewer cases of anaphylaxis than iron
polymaltose, it is expensive and there
are PBS-restrictions on its supply.8
There are other iron preparations
available internationally, for example, a
new preparation iron carboxymaltose,
can be given as 1,000 mg over
15 minutes and thus far, appears
to have a low risk of serious
adverse reactions.12
The fear of adverse effects that
accompanies parenteral iron therapy
is probably unnecessary due to the
low rate of serious adverse effects
provided appropriate supportive
therapy is available should a rare
anaphylactic reaction occur.
Vol. 30 – June #06
Calculating parenteral iron dosing
Total dose infusion, where the
total amount of iron required for
replacement is administered in
one infusion, can only be used for
patients receiving iron polymaltose.12,13
A maximum of 2,500 mg can be given
as an IV infusion in 500 mL of 0.9%
sodium chloride.8,13 Iron polymaltose
may also be given intramuscularly
502
at a dose of 100 mg every second
day until the total dose is reached.8
Administration protocols vary and local
guidelines should be followed.
As published in the manufacturer’s
product information, the dose required
of iron polymaltose complex needed
to correct deficiency can be calculated
using the Ganzoni formula:13
Iron dose (mg) = bodyweight (kg) x
[target Hb – actual Hb (g/L)] x 0.24 +
iron depot
The Gastrointestinal Therapeutic
Guidelines contains a table
which provides guidance on the
recommended dosing of iron
polymaltose, based on calculations
using the Ganzoni formula.8
The potential for intravenous iron
administration to cause serious
adverse effects can be minimised
by the use of a test dose or
commencing infusions slowly which
is recommended in various hospital
protocols.8,9,19
For iron sucrose, a test dose of
20 mg is diluted to a maximum of
20 mL in 0.9% sodium chloride and
administered over 15 minutes.20 The
recommended dilution for treatment
doses is 100 mg iron sucrose diluted
to 100 mL with 0.9% sodium chloride
and administered by IV infusion over
15 minutes with dilution occurring
immediately before administration.20
Iron infusions should not be mixed
with other agents due to the potential
for production of toxic compounds.13
Other treatments
Where patients have severe
iron deficiency anaemia, a blood
transfusion should be considered
and is recommended when the
haemoglobin level is below 70 g/L.3,21
Erythropoietin (EPO) agonists
stimulate erythropoiesis which
leads to an increase in reticulocyte
count and therefore increases the
concentration of haemoglobin and
haematocrit in the blood.22 They are
indicated in some forms of anaemia,
including anaemia of chronic renal
failure, but their use for uncomplicated
iron deficiency anaemia is not
widespread due to expense and
safety concerns.22
Case discussion
It is likely that some of the signs
and symptoms that Jennifer is
experiencing (e.g. lethargy, pallor and
hair-loss) are at least in part due to
iron deficiency anaemia.
The dose of Metamucil that Jennifer
is taking is less than adequate as a
fibre supplement and is unlikely to
treat her constipation at this stage;
but may be useful as a prevention
therapy in an adequate dose once
constipation is resolved.23 Jennifer
was considerably constipated, as
indicated by her description of hard
stools that are difficult to pass
despite adequate water consumption.
The senna she has been taking
has not been effective, possibly
due to the difficulty of passing the
stool. It may be beneficial to try a
laxative that increases fluid content
of the stool such as a polyethylene
glycol laxative.24,25
Lifestyle changes would be beneficial
to Jennifer including restarting of
an exercise program and increasing
the total consumption of food
especially those foods rich in fibre
(e.g. vegetables, fruits, rye and
barley) and iron (e.g. red meat,
chicken and spinach).26 Inadequate
water consumption is not likely to be
contributing to her constipation as she
already consumes two to three litres
of water daily.
Actions and
recommendations
Due to Jennifer’s inability to tolerate
oral iron supplements, and in
preparation for her imminent surgical
procedures, administration of IM
iron supplementation should be
considered; as this can be given in
an appropriately equipped general
practice. Correct injection technique
is vital to reduce the risk of persistent
skin discolouration and pain.13
Detailed instructions are provided
in manufacturer’s information and
includes advice on injection site,
length of needle, vertical needle
insertion, application of pressure after
injection and encouraging movement
of the patient after injection.13
For treatment of Jennifer’s
constipation it was suggested that
an osmotic laxative such as Movicol
be used to increase the fluid content
within the stool.27 She was advised to
use the powdered form of Metamucil
and to take the recommended amount
to ensure appropriate dosing, as well
as maintaining her water intake.
medication review
The articles in this series are independently researched and compiled by PSA commissioned authors and peer reviewed.
Jennifer agreed to start walking every
day in an attempt to regain her fitness,
promote sleep and help constipation.
She also said that she would increase
her food intake, particular of iron- and
fibre-rich foods as she understood that
this would assist in recovering from
anaemia and constipation and would
make the use of the multivitamin
unnecessary.
Continuing Professional Development
Outcomes
At this stage the doctor wished
to continue monitoring Jennifer’s
haemoglobin and haematocrit;
rather than actively manage her
iron deficiency anaemia with IM
administration of iron (either in the
surgery or on referral to hospital
due to concern over the potential
for adverse reactions). The doctor
was informed about the actual rate
of reaction, but wished to have this
addressed in hospital when Jennifer
was next admitted for surgery. It was
also mentioned in the report that
serum iron, ferritin and TIBC should
also be monitored; as these are more
indicative of iron deficiency anaemia,
whereas low levels of haemoglobin
and haematocrit can occur with other
forms of anaemia.2
The doctor acknowledged the need to
treat Jennifer’s constipation especially
considering the plan for more surgical
treatment further increasing the risk of
constipation. He suggested that she
return to her community pharmacy to
purchase Movicol and adjust her diet
as had been recommended.
Jennifer mentioned on one of her
visits to the pharmacy that her
appetite had increased and she was
feeling much better.
Summary
Parenteral iron administration is
currently avoided due to the fear of
serious adverse effects from the
treatment. In reality, the incidence of
serious adverse effects is minimal and
in an appropriately equipped setting
can be undertaken safely and should
be considered as an alternative in
patients who do not get the required
results from oral iron administration or
who cannot tolerate oral iron therapy.
References
1. Iron Deficiency. Sydney: Gastroenterological Society of
Australia. Digestive Health Foundation. 2008.
2. Conrad ME. Iron deficiency anaemia. Medscape; 2009
[updated Sep 2010]; At: http://emedicine.medscape.
com/article/202333-overview.
3. Hughes J, Tenni P, Soulsby N. Full blood picture. In:
Hughes J, ed. Case Studies In Clinical Practice: Use
of Laboratory Test Data: Process Guide and Reference
for Healthcare Professionals – second edition:
Pharmaceutical Society of Australia. 2009;153–82.
4. Iron deficiency and megaloblastic anaemias. In: Helms
RA, Quan DJ, eds. Textbook of Therapeutics: Drug
and Disease Management. Eighth ed. Philadelphia:
Lippincott Williams and Wilkins; 2006;771–98.
5. Lichtin AE. Iron deficiency anaemia. The Merck Manual
Online Medical Library; 2008 [cited 2010 Sep]; At:
www.merck.com/mmpe/sec11/ch130/ch130b.html.
6. Pagana KD, Pagana TJ. Diagnostic and laboratory
test reference. Ninth ed. St. Louis, Missouri: Mosby
Elsevier; 2009.
7. Naim M, Hunter J. Intravenous iron replacement. Aust
Fam Physician. 2010;39(11):839–41.
8. Therapeutic Guidelines: Iron deficiency [CD].
Melbourne: Therapeutic Guidelines; 2011.
9. Australian Medicines Handbook: Iron. Adelaide:
Australian Medicines Handbook; 2011 [cited 2011 Apr].
10. Australian Medicines Handbook: Drug interactions
index: iron. Adelaide: Australian Medicines Handbook;
2011 [cited 2011 Apr].
Questions 1) Signs and symptoms of iron
deficiency anaemia include:
Vol. 30 – June #06
a) diarrhoea, stomach cramps and
nausea.
b) fatigue, lethargy and hair loss.
c) shortness of breath, elevated blood
pressure and insomnia.
d) fever, rash and angioedema.
2) What initial recommendation is
MOST SUITABLE for a patient
who suffers from nausea and
stomach pains after taking oral
iron supplementation?
a) Advise the patient to stop taking
iron therapy.
b) Advise the patient to take the iron
supplement with food.
504
11. Dodds A. Iron deficiency anaemia. NPS News.
2010;70:1–4.
12. Pasricha SS, Flecknoe-Brown SC, Allen KJ, Gibson
PR, McMahon LP, Olynyk JK, et al. Diagnosis and
management of iron deficiency anaemia: a clinical
update. MJA. 2010;193(9):525–32.
13. eMIMS: Prescribing Information: Ferrum H Monograph.
St Leonards, NSW: MediMedia Australia; 2010 [cited
2011 Apr].
14. Hayat A. Safety issues with intravenous iron
products in the management of anaemia in chronic
kidney disease. Clinical Medicine and Research.
2008;6(3/4):93–102.
15. Aronoff GR. Safety of intravenous iron in clinical
practice: implications for anaemia management
protocols. J Am Soc Nephrol. 2004;15:s99–106.
16. Hamilton W, Sharp D. Diagnosis of colorectal cancer
in the primary care: the evidence base for guidelines.
Family Practice. 2004;21:99–106.
17. Newnham E, Ahmad I, Thornton A, Gibson PR. Safety
of iron polymaltose given as a total dose iron infusion.
Intern Med J. 2006;36(10):672–4.
18. Singh K, Fong YF, Kuperan PA. A comparison between
intravenous iron polymaltose complex (Ferrum
Hausmann) and oral ferrous fumarate in the treatment
of iron deficiency anaemia in pregnancy. Eur J
Haemotol. 1998;60:119–24.
19. Iron polymaltose infusions discussion paper: Rapid
response to iron polymaltose infusion e-mail
discussion. NSW Therapeutic Advisory Group; 2008;1.
20. eMIMS: Prescribing Information: Venofer Monograph.
St Leonards, NSW: MediMedia Australia; 2010 [cited
2011 Apr].
21. Clinical practice guidelines on the use of blood
components. Canberra: National Health and Medical
Research Council and Australiasian Society of Blood
Transfusion; 2001.
22. Australian Medicines Handbook: Erythropoietin
agonists. Adelaide: Australian Medicines Handbook;
2011 [cited 2011 Apr].
23. Metamucil fibrecaps. Metamucil; [cited 2011 Apr]; At:
www.metamucil.com.au/products_fibrecaps.php.
24. Australian Medicines Handbook: Constipation.
Adelaide: Australian Medicines Handbook; 2011 [cited
2011 Apr].
25. Prevention and treatment of opioid-induced
constipation. Australian Pharmaceutical Formulary. 21st
ed: Pharmaceutical Society of Australia, 2009;316–7.
26. Constipation guide. Australian Pharmaceutical
Formulary. 21st ed. ACT: Pharmaceutical Society of
Australia; 2009;375–9.
27. eMIMS: Prescribing Information: Movicol Monograph.
St Leonards, NSW: MediMedia Australia; 2010 [cited
2011 Apr].
A score of 4 out of 5 attracts 1 CPD credit.
c) Refer the patient to the doctor as
these symptoms are only caused
by gastroenteritis.
d) Refer the patient to the doctor for
parenteral iron therapy.
3) Which of the following
statements is TRUE?
a) Iron carboxymaltose is a new iron
preparation, but has a high rate of
adverse effects.
b) Iron sucrose can be given IM or IV.
c) A test dose of IV iron, or
introducing the infusion slowly, is
recommended at the beginning
of an IV infusion to minimise the
potential for anaphylaxis.
d) Iron polymaltose complex cannot
be given as a total dose infusion.
4) The rate of anaphylaxis with IV
iron administration is:
a) 0.7% with ferric gluconate.
b) 0.002% with iron polymaltose
complex.
c) 0.7% with iron sucrose.
d) 0.002% with iron sucrose.
5) The most reliable indicator of
iron deficiency anaemia is:
a) ferritin.
b) transferrin.
c) haemoglobin.
d) haematocrit.