Ferric carboxymaltose (FCM) is the latest parenteral iron preparation to be subsidised by the Pharmaceutical Benefit Scheme (PBS) for patients with iron deficiency anaemia (IDA) when oral therapy has failed or cannot be used. This is welcome news to private hospital operators, healthcare professionals and patients, due to the cost of treatment now being reduced from in excess of $300.00 to a co-payment of $6.00 for concessional patients and $36.90 for general patients. Additionally, the use of FCM can help preserve valuable nursing resources and provides a more comfortable manner of administration to patients, as it can be administered in one large single dose (up to 1000mg) over 15 minutes.

One in 22 Australians aged 18 years and over are at risk of anaemia and older people (over 65 years) are four times more likely to suffer from anaemia than the general population according to the National Health Measures Survey (NHMS) 2011-12. At risk populations are identified by measuring the haemoglobin (Hb) level in the blood. An adult is considered to be at risk of anaemia when the Hb level falls below the reference range, that is; less than130g/L for males, less than 120g/L for females and less than 110g/L for pregnant women.

Iron deficiency is the most common cause of anaemia. Any condition that causes blood loss (e.g. abnormal uterine bleeding), increases iron utilisation (e.g. pregnancy) or reduces iron absorption (e.g. inflammatory bowel disease) can lead to iron deficiency. This is because dietary intake of iron is poorly absorbed and can barely keep up with the regular daily demand of the body.

The management of IDA should include treatment of the underlying condition as well as restoring iron stores in the body. Oral iron supplementation is the initial treatment of choice as it is easy to administer and non-invasive. However, parenteral iron may be required when the oral supplement is ineffective or unsuitable. Iron polymaltose complex (Ferrum H®, Ferrosig®), iron sucrose complex (Venofer®) and ferric carboxymaltose (Ferinject®) are the three parenteral preparations currently available in Australia for the treatment of IDA.

Ferric carboxymaltose is a colloidal complex of a polynuclear iron (III)-oxyhydroxide core with carboxymaltose ligands which provides slow and controlled release of iron to iron-binding proteins and does not react with dextran antibodies. Therefore, patients treated with FCM have a lower risk of allergic reactions compared to those treated with iron dextran and a test dose is not required prior to administration. The FCM formulation also has the favourable biochemical characteristics of near neutral pH and physiological osmolarity, which allow up to 1000mg of FCM to be given as a single dose and in short infusion time.

The efficacy of FCM in treating iron deficiency anaemia has been assessed in a wide range of conditions. One trial of 291 subjects with postpartum IDA compared FCM given intravenously once a week (until the Ganzoni cumulative dose was reached) to oral ferrous sulfate 325mg TDS for six weeks. 91.4% of subjects in the FCM group, compared to 66.7% of subjects in the ferrous sulfate group, achieved Hb levels greater than 120g/L at the conclusion of the study. FCM is also more likely than oral ferrous sulfate to increase Hb greater than 30g/L (91.4% vs. 64.6%).

FCM was also investigated in patients suffering from iron deficiency anaemia secondary to inflammatory bowel disease (IBD). A randomised trial was conducted in IDA patients with IBD to compare the efficacy of FCM (three injections at one week intervals to reach each the total calculated dose) against oral ferrous sulfate (304mg BD for 12 weeks). The median Hb level improved from 87 to 123g/L in the FCM group compared to 91 to 121g/L in the ferrous sulfate group after 12 weeks, proving that FCM is effective in treating IDA secondary to IBD. Another finding from this trial was that patients in the FCM group experienced a significantly faster increase of their Hb level than patients in the ferrous sulfate group, as measured at week two and week four of the trial.

An open label randomised trial was conducted to compare the efficacy of FCM and iron sucrose in haemodialysis patients with IDA. Patients were randomised to receive either 200mg of FCM or 200mg of iron sucrose two to three times a day until the calculated cumulative dose was reached. At week four, 44.1% of patients in the FCM group and 35.3% of patients in the iron sucrose group had Hb level increases of at least 10g/L. This trial demonstrated that FCM has comparable efficacy to iron sucrose in treating haemodialysis patients with IDA.

There are two methods to calculate the cumulative FCM dose required to correct iron deficiency. The first method is the Ganzoni method, which takes into account the patient’s body weight, current iron stores and Hb deficit. The second method is the simplified method, which can only be used in patients with a body weight of 35kg or more. The cumulative FCM dose can be determined by using Table 1 below.

Table 1. Simplified method to determine cumulative iron dose for ferric carboxymaltose.

Hb g/L Body weight 35 to 69kg Body weight ≥ 70kg
< 100 1500mg 2000mg
≥ 100 1000mg 1500mg

 

FCM is administered by the intravenous route, either as an injection of undiluted solution or an infusion diluted with normal saline. FCM is proven to be compatible in polyethylene and glass containers only. Therefore, other containers such as PVC should not be used for dilution. The maximum dose of FCM is 1000mg per week (up to a maximum of 20mg/kg) and may be administered as a single dose over 15 minutes. For patients requiring more than 1000mg of FCM, an additional dose is recommended at least one week after the previous dose. Following FCM administration, patients are advised not to begin oral iron therapy for at least five days, as oral iron absorption is reduced when used concomitantly.

The common adverse drug reactions reported are headache, dizziness, hypertension, abdominal pain, constipation or diarrhoea, and injection site reactions. In some patients, an increase in alanine aminotransferase and decrease in blood phosphorus level has also been reported. Allergic reactions (including anaphylactic reactions) are uncommon for FCM, occurring with a probability of less than one in 100.

Utilisation of FCM in the treatment of IDA has the potential to increase efficiency in hospitals as it can be injected in a large single dose (up to 1000mg) over 15 minutes, with no test dose required. In comparison to other treatment options such as iron polymaltose, which requires long infusion times (up to five hours), or iron sucrose, with safety limits for single doses, FCM appears to be more advantageous. FCM provides a more comfortable manner of administration for patients and allows preservation of valuable nursing and medical staff resources in hospitals.

Editor’s note: To read more about Parenteral Iron therapy, click here.

References:

  1. Australian Bureau of Statistics. Anaemia. In: Australia Health Survey: Biomedical results for chronic diseases, 2011-12. Cat, no. 4364.0.55.005; 2013.
  2. Bailie GR, Mason NA, Valaoras TG. Safety and tolerability of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Haemodial Int. 2010; 14(1): 47-54.
  3. Bailie GR. Efficacy and safety of ferric carboxymaltose in correcting iron-deficiency anemia: a review of randomized controlled trials across different indications. Arzneimittelforschung. 2010; 60(6a): 386-98.
  4. Ferinject (ferric carboxymaltose) Australian approved product information. South Bank: Vifor Pharma Pty Ltd. Approved 05 April 2011, amended 21 December 2012.
  5. Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol 2008; 103(5): 182-92.
  6. Porter RS (ed). The Merck Manual for Healthcare Professionals (Internet). Whitehouse Station: Merck Sharp & Dohme Corp; 2012.
  7. Seid MH, Derman RJ, Baker JB, Banach W, Goldberg C, Rogers R. Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomised controlled clinical trial. Am J Obstet Gynecol 2008;199(4): 435
  8. Therapeutic Goods Administration (TGA). Australian Public Assessment Report for Ferric Carboxymaltose. Woden: TGA; 2011.

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