subcutaneous discolouration and have been associated with soft tissue sarcomas. 2, 7
When older iron dextran preparations were used, parenteral iron infusions were frequently complicated by fevers, arthralgia, hypotension, anaphylaxis and even death. 2 Newer intravenous iron preparations, such as iron carboxymaltose, iron polymaltose and iron sucrose, have significantly reduced the incidence and severity of serious adverse reactions. 2, 4, 7, 8 However, up to 26 % of patients report minor, short-lived side effects— including headache, fevers and arthralgia— for up to two days following the infusion. 2 These infusions can only be given under medical supervision with immediate access to resuscitation equipment. 7
There are currently four TGAlicenced parenteral iron preparations available in Australia( see table 5).
Two iron polymaltose preparations are available,( Ferrum H and Ferrosig). 9, 10 These preparations can deliver a‘ total-dose’ of iron to replenish iron stores in one infusion. They need to be infused over five hours to minimise the risk of serious reactions such as anaphylaxis. 9, 10 The total dose of iron required for a patient is calculated based on the severity of the iron deficiency and the patient’ s ideal body weight based on the Ganzoni equation( see box 2).
Iron sucrose( Venofer) is currently only funded for iron-deficient patients with chronic kidney disease who are receiving erythropoietinstimulating agents. This product cannot be given as a single dose because of the release of vasoactive iron; therefore, it needs to be given in multiple, smaller doses, usually during dialysis sessions. 9, 10
The latest intravenous iron preparation released in Australia is iron carboxymaltose( Ferinject). This preparation also allows a‘ totaldose’ infusion( up to 1000mg) to be given over 15 minutes, with a low risk of serious adverse reactions. It can also be given as frequent, smaller bolus doses, up to 200mg several times per week, until body iron stores are replete. 9, 10 The rapidity of infusion has clear benefits to both the patient and the ambulatory care provider, such as outpatient clinics or iron infusion centres.
Table 4. Examples of oral iron preparations with adequate elemental iron 2, 4, 7
Product information Price
Ferro-tab( 65.7mg elemental iron) Film-coated tablet
FGF( 80mg elemental iron + 300mcg folic acid) Controlled-release tablet
Fefol( 87.4mg elemental iron + 300mcg folic acid) Capsule containing delayed-release pellets
Ferro-F-Tabs( 100mg elemental iron + 350mcg folic acid) Film-coated tablet
Ferro-Gradumet( 105mg elemental iron) Controlled-release tablet
Ferrograd C( 105mg elemental iron + 500mg Vitamin C) Controlled-release tablet
Ferro-Liquid( 30mg of elemental iron / 5mL) Oral liquid
Box 2. Ganzoni equation
Total body iron deficit / cumulative iron dose( mg) = body weight *( kg) x( target Hb – actual Hb in g / L) x 0.24 ** + iron depot( mg)***
* Use ideal body weight in overweight patients. If underweight, use actual body weight
** The factor 0.24 = 0.0034 x 0.07 x 1,000: For this calculation the iron content of haemoglobin = 0.34 %, blood volume = 7 % of the bodyweight, and 1000 is the conversion from g to mg
***Iron depot < 35kg body weight iron depot = 15mg / kg body weight ≥ 35kg body weight iron depot = 500mg Source: National Blood Authority Iron Product Choice and Dose Calculation for Adults. Australian Government.
$ 17 for 60 tablets * PBS listed
$ 4 per 30 tablets
$ 10 per 30 tablets
$ 18 per 60 tablets
$ 7 per 30 tablets
$ 8 per 30 tablets
$ 21 per 250mls
NOTE: This list may not be comprehensive. Sources: Pasricha, et al. Medical Journal of Australia 2010; 193:525-32; Camaschella C. New England Journal of Medicine 2015; 372:1832-43; Gastrointestinal Therapeutic Guidelines Ltd( eTG March 2017 edition).
Figure 9. Ultrasound scan twin pregnancy, eight weeks.
Source: Nevit Dilmen http:// bit. ly / 2f3KeGa
Treatment of iron deficiency during pregnancy The Royal Australia and New Zealand College of Obstetricians and Gynaecologists, recommend all pregnant women have a full blood count at their first antenatal visit and again at 28 weeks’ gestation. 11 If anaemia is detected, it should be investigated and treated. They do not recommend routine iron supplementation for all women during every pregnancy, but suggest consideration in women at‘ high-risk’ of developing iron deficiency, namely vegetarians / vegans and those with a multiple pregnancy( see figure 9). 11
The recently published‘ Obstetric and Maternity’ module of the Patient Blood Management Guidelines recommend a‘ therapeutic dose’ of oral iron supplementation( 100-200mg elemental iron daily) to all maternity patients with confirmed iron deficiency anaemia. 12 They encourage regular monitoring of the woman’ s response, and if inadequate, they endorse the use of parenteral iron from the second trimester, but not via the intramuscular route if possible. 12
Furthermore, they strongly encourage clinicians to calculate the dose of parenteral iron required for each woman based on her iron deficit to prevent under dosing. Paradoxically, these guidelines suggest consideration of low-dose elemental iron supplementation( 20-80mg daily) in iron deficient, but not anaemic, maternity patients following a study that suggested this approach may increase compliance by improving tolerability. 12
Iron supplementation should continue for a minimal of three months after the normalisation of the haemoglobin, or for at least six weeks post-partum. However, if the haemoglobin is below 100g / L postpartum, oral iron supplementation should continue for a further three months. Cessation of iron supplementation should take into account any ongoing iron loss associated with breast feeding.
Response to iron replacement The full treatment effect on the haemoglobin may not been seen for several weeks to months, depending on the degree of iron deficiency and the adequacy of iron supplementation. However, most patients report an improvement in their general wellbeing within days of starting iron replacement therapy.
This usually correlates with a reticulocytosis within a week of adequate iron replacement, followed by sequential increases in the haemoglobin of up to 10-20g / L over the next 1-3 weeks. 2, 4, 7, 8 This is equivalent to the haemoglobin rise seen after a transfusion of 1-2 units of red blood cells.
Iron replacement therapy should continue for 3-6 months after the correction of anaemia for adults and 2-3 months for children to ensure iron stores are replete with normal serum ferritin levels. 2, 4, 7, 8
Table 5. Examples of TGA- licenced intravenous iron preparations
Product Price Considerations
Ferrosig Adult dose: variable from 200mg to 1000g Iron polymaltose complex IV as per protocol
Ferrum H Adult dose: variable from 200mg to 1000mg iron polymaltose complex IV as per protocol
Venofer Adult dose( renal dialysis only): 100mg to 200mg iron sucrose IV given over sequential dialysis session to a total of 1000mg
Ferinject Adult dose: variable from 200mg to 1000mg ferric carboxymaltose given as a 15min infusion
Table 6. Troubleshooting: Why has my patient with a microcytic, hypochromic anaemia not responded to oral iron supplementation?
Reason for nonresponse
Options to consider
Coexisting disease, decreasing bone marrow response to iron
Incorrect diagnosis
Abnormal gastrointestinal absorption of iron
Continued, excessive blood loss
Non-adherence to oral iron
Aiming for a serum ferritin level of at least 50-100 µ g / L should prevent the development of recurrent iron deficiency, if the underlying cause of the iron deficiency has been identified and managed.
Ongoing monitoring of the adequacy of iron replacement is vital. The frequency of this monitoring is dependent on the severity of the iron deficiency, response to iron supplementation, sustained correction of the underlying contributors to the iron deficiency, and the accuracy of estimating ongoing iron requirements. Failure to respond to iron therapy should raise suspicion of ongoing bleeding, poor compliance, incorrect dose of elemental iron replacement or incorrect diagnosis( see table 6).
Blood transfusion and iron deficiency A blood transfusion is an inappropriate treatment for patients with compensated iron deficiency anaemia. 2, 4, 7, 8 Blood transfusion should only be considered in patients with end-organ compromise secondary to severe anaemia, or with significant ongoing bleeding with haemodynamic compromise, and must always be followed by an iron infusion to replenish iron stores.
$ 25 for 100mg / 2mL
$ 25 for 100mg / 2mL
$ 40 for 100mg / 5mL
$ 300 for 500mg / 10mL
Pregnancy Category A Contraindicated in first trimester
Pregnancy Category B3 Contraindicated in first trimester
Pregnancy Category B3 Limited evidence
Pregnancy Category B3 Limited evidence
Sources: Pasricha, et al. Medical Journal of Australia 2010; 193:525-32; Gastrointestinal Therapeutic Guidelines Ltd( eTG March 2017 edition); MIMS Australia 2017; Australian Government Department of Health: Therapeutic Goods Administration.
Infection Chronic inflammation Malignancy Other nutritional deficiencies such as B12, folate
Thalassemia Lead or copper poisoning Severe zinc deficiency Myelodysplastic syndrome
Malabsorption due to coeliac disease, inflammatory bowel disease Other compounds reducing absorption, eg, antacids, tea, fibre Enteric-coated iron tablets Rapid intestinal transport past duodenum, eg, surgery
Occult GI malignancy Peptic ulcer disease or H. pylori infection Active inflammatory bowel disease
Prescription not filled Patient ceased therapy
Source: Pasricha, et al. Medical Journal of Australia 2010; 193:525-32; Australian Red Cross Blood Service: Iron Deficiency Anaemia( see: www. transfusion. com. au)
Online resources
Gastrointestinal Therapeutic Guidelines: Iron Deficiency www. tg. org. au
Australian Red Cross Blood Service: Iron Deficiency Anaemia www. transfusion. com. au
National Blood Authority: Patient Blood Management Guidelines Modules 2-6 www. blood. gov. au / pbm-guidelines
Ganzoni equation http:// bit. ly / 2jkt9ZR
National Blood Authority Iron Product Choice and Dose Calculation for adults http:// bit. ly / 2wTY3gX
References
Available on request from howtotreat @ adg. com. au
cont’ d next page
www. australiandoctor. com. au 27 October 2017 | Australian Doctor | 25