Parenteral Iron in Adults >18 Years

Notes on Oral Iron Therapy

1. Patients with established IDA should be given 100-200mg of elemental iron daily
2. Choice of iron preparation is based on cost and incidence of side effects. There is little difference in efficiency of absorption of iron between the different salts.
3. Modified release preparations have no therapeutic advantage and the low incidence of side effects could be attributed to the lower absorption levels of iron associated with their use.
4. Side effects of iron tablets include nausea, constipation and diarrhoea but this can usually be managed by dose reduction.
5. Ferrous fumarate 305mg twice daily in the form of ‘Fersaday’ capsules or 322mg twice daily as ‘Galfer’ tablets are the most cost-effective choices of iron preparation.
6. Iron salts should be given orally until the haemoglobin level is within the reference range and then maintained for 3 months to replenish iron stores. After this the iron can be stopped (BGS guidelines).
7. If there is an inadequate response to therapy patient compliance should be assessed.
8. If the iron treatment is not tolerated adverse effects should be addressed by:
   • reducing the dose frequency of the iron supplement eg one tablet alternate days for those with GI upset,
   • recommending the patient takes iron with or after meals,
   • giving a different iron formulation/salt with a lower content of elemental iron
   • offering reassurance to patients who have black stools,
   • offering a laxative to patients with constipation

Indications for Parenteral Iron

1. Oral iron not tolerated, or has shown to be ineffective, or serious non-compliance is a problem.   Iron preparation with low content of elemental iron should be considered prior to consideration of infusion.
2. Patients with heart failure with reduced ejection fraction, New York Heart Association (NYHA) class III with an left ventricular ejection fraction (LVEF) ≤45%, or NYHA class II, LVEF ≤40%, who have a Hb level of 95 to 135g/L and iron deficiency (defined as ferritin <100 micrograms/L or ferritin <300micrograms/L if TSAT<20%).
3. Pre-operative Hb optimisation for patients having surgery with expected blood loss of >500ml or >10% total blood loss.  Target Hb concentration of ≤130g/L.
4. Patients with chronic iron deficiency associated with CKD, or other long term conditions in which oral iron is unsuitable eg patients using EPO.
   NB for most patients, parenteral iron does not produce a significantly faster haematological response than oral iron. See Parenteral Iron for Non-HD CKD Patients

Contraindications for Parenteral Iron

1. Non iron deficiency anaemias, e.g. haemolytic anaemia
2. Iron overload or disturbances in utilisation of iron, e.g. haemochromatosis, haemosiderosis.
3. History of hypersensitivity to parenteral iron or excipients.
4. History of asthma, eczema or anaphylactic reactions, as such patients are more likely to have allergic reactions. It may be possible to use Cosmofer by the intramuscular route in these patients but please ask for advice from a pharmacist before deciding on this option.
5. Decompensated hepatic cirrhosis or hepatitis.
6. Acute or chronic infections which may be exacerbated by parenteral iron
7. Acute kidney injury
8. Rheumatoid arthritis with signs or symptoms of active inflammation.
9. First trimester of pregnancy.
10. Patients with thalassaemia or sickle cell disease – refer to haematologist.

Allergic Reactions

1. The administration of parenteral iron can cause allergic or anaphylactoid reactions which may be potentially fatal and can occur with the first dose or with any subsequent doses.   Each IV iron administration is associated with a risk of hypersensitivity reaction, therefore the number of IV iron administrations should be kept to a minimum.
2. The warnings about this were strengthened in 2013 by the European Medicines Agency.   Click here for EMA Recommendations to manage risk of allergic reactions with intravenous iron-containing medicines 2013. [pdf]
3. Mild allergic reactions should be managed by stopping the iron infusion and administering antihistamines
4. Hypotensive episodes may occur if the iron is administered too rapidly. Patients with low iron binding capacity and/or folate deficiency are at particular risk.
5. Patients must be observed closely during and post infusion and should be provided with a leaflet to take away which explains how to deal with any delayed reactions after discharge.

Interaction with Oral Iron Preparations

1. Combined treatment with oral and IV iron may lead to the appearance of highly toxic non transferrin bound iron. Oral iron therapy should generally not be required following IV iron replacement
2. It is recommended that oral iron preparations are discontinued at least 48 hours prior to IV iron infusions.
3. The need for oral iron therapy should be reviewed following IV iron replacement. If deemed necessary, oral iron should not be started for at least 5 days after the last IV iron infusion.

Cosmofer (Iron Dextran)

1. CosmoFer is available in ampoules of 2ml, 5ml or 10ml containing 50mg/ml iron solution for infusion or injection. The total dose must be diluted in either 500ml of 0.9% sodium chloride or 5% glucose before intravenous infusion.
2. The dose of Cosmofer required to raise Hb to 111g/l varies according to body weight and pretreatment Hb in the range 500-1700mg eg dose for a 70kg patient with baseline Hb 70g/l is 1100mg
3. Up to 20mg/kg can be given as a single dose
4. If you add 1000mg (2x10ml vials) Cosmofer to 500ml saline you have a concentration of 2mg/ml.
5. Give a test dose of 1ml/min for 12 minutes then observe for 30 mins to ensure no reaction
6. Follow this with remaining infusion at 100ml/hr for 5 hours then observe for a further 30 mins before allowing home.

Monofer (Iron isomaltoside 1000)

1. Given as a total dose infusion and administered as a single dose of up to 20mg/kg body weight. Doses up to 1g must be infused over at least 15 min. Doses exceeding 1g must be infused over at least 30 minutes.
2. If the total iron dose exceeds 20 mg iron/kg body weight, the dose must be split in two administrations with an interval of at least one week.
3. Suitable for out-patients due to shorter infusion time or for in-patients who may be discharged on the same day as the infusion.

Diafer (Iron isomaltoside 1000)

1. This is licensed only in adults for the treatment of iron deficiency in patients with chronic kidney disease on dialysis
2. It is given in doses up to 200mg either as an intravenous bolus dose or during dialysis via the dialyser. Protocols are in place at the Renal Unit so the detail is not discussed in this document.
3. For patients in whom a total dose infusion is not suitable and who are not dialysis patients, it may be possible to obtain Venofer to administer in smaller intermittent doses but this is not routinely stocked. Please speak to the Clinical Pharmacists for advice.

Links

1. Guidance on Cosmofer [pdf]
2. Guidance on Monofer [pdf]

Content by Susan Coyle and Nikki Cameron