Parenteral Iron

Introduction

Iron supplements may be used to treat anaemia. Anaemia is a relatively common problem and according to the World Health Organisation (WHO), anaemia is characterised by a haemoglobin (Hb) level below the minimum of the usual reference range; that is less than 130g/L in men, 120g/L in women, and 110g/L in pregnant women and pre-school children. Signs and symptoms will usually appear when the Hb falls below 100g/L.

Australians at increased risk of iron deficiency anaemia (IDA) include children, and women of child-bearing age, especially those women who are pregnant. The WHO estimates up to 10% of pre-school children, and 10-15% of women in their reproductive years may be suffering from anaemia.

In Australia, most cases of anaemia are related to a deficiency of the crucial nutrients iron, vitamin B12 and folic acid, combined with high physiological requirements, or are related to blood loss.

Blood loss may be the result of gastrointestinal irritation, menstruation, blood donation, or other causes. Anaemia of chronic disease may affect hospitalised or institutionalised patients.

The majority of people with IDA will be managed on oral therapy, but some may require parenteral therapy if they are intolerant of oral preparations or have poor uptake of oral iron therapy.

Parenteral Therapy

Parenteral administration describes anything taken into the body, or administered, in any manner other than via the digestive system. There are three iron preparations available in Australia for parenteral use:

1. Iron polymaltose complex (Ferrum H^®, Ferrosig^®): contains 100mg iron in each 2mL ampoule;
2. Iron sucrose complex (Venofer^®): contains 20mg iron/mL (i.e. 100mg elemental iron/5mL ampoule); and
3. Ferric carboxymaltose (Ferinject^®): contains 100mg iron in 2mL.

Ferrum H^® and Ferrosig^® are both available on the Pharmaceutical Benefits Scheme (PBS). However, Venofer^® is currently only available on the PBS as an authority prescription for iron deficiency in renal patients on chronic haemodialysis, who are having epoetin or darbepoetin, and who have a documented hypersensitivity to the polymaltose formulation. Ferinject^® is not currently available on the PBS.

Administration

Only iron polymaltose can be given by intramuscular (IM) injection and Ferrum H^® is licensed for administration by this route, where Ferrosig^® is also licensed for intravenous (IV) infusion.

There is some debate as to whether Ferrum H^® can also be used intravenously. Ferrum H^® has been administered for IV use in many facilities for a number of years without any issues, but it is not indicated for IV use in the product information, and therefore any IV administration is considered to be off license.

The intramuscular route is reserved for use in situations when an intravenous infusion is not practical. Intravenous administration is the preferred route, as even though intramuscular administration of iron is effective; it is poorly absorbed, local reactions (particularly pain and subcutaneous discolouration) occur frequently at the injection site, and it is no safer than IV administration. It should never be injected into the arm or other exposed areas due to the risk of persistent discolouration of the skin.

There is a specific technique for administration; the Hochstetter method. The manufacturer’s product information provides information and diagrams for using the Hochstetter method. This is important in order to avoid pain and minimise skin staining.

Other adverse effects include local inflammation with inguinal lymphadenopathy, and lower quadrant abdominal pain.

Intravenous infusions of iron polymaltose (Ferrosig^®), iron sucrose (Venofer^®) and ferric carboxymaltose (Ferinject^®) injections have different dosing regimens, different infusions rates, and are not interchangeable.

Allergic Reactions

There has been concern regarding severe allergic reactions associated with IV administration of iron but these have been largely allayed. A safety audit on 400 infusions of the polymaltose formulation used across Australia identified only minor side effects during the actual infusion process, whilst approximately 25% of patients experienced headache, fever and arthralgias up to two days after the infusion. It is still advised that IV administration is conducted at sites such as hospitals, which have the skills and equipment to manage any severe allergic reactions, should they occur.

Iron polymaltose and ferric carboxymaltose are given as a total dose infusion. The incidence of cross reactivity is unknown and therefore patients allergic to iron polymaltose should not receive ferric carboxymaltose, without prior consultation with an expert.

Iron sucrose (Venofer^®) is given as multiple smaller doses, usually 100-200mg, by slow IV injection, rather than as an infusion. It gives a more rapid rise in Hb. Due to restrictions on the PBS it is not commonly used in Australia, but it is widely used overseas for treatment of IDA and has a good safety profile.

Oral therapy may be necessary after an iron infusion, but should not be (re)started until at least one week after the last iron infusion.