Ferric carboxymaltose

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Ferinject (Vifor Pharma)
2 mL solution containing 100 mg iron and 10 mL solution containing 500 mg iron for infusion
Approved indication: iron deficiency
Australian Medicines Handbook section 7.5.2

Intravenous ferric carboxymaltose is indicated for iron deficiency when oral preparations are ineffective or not tolerated. The molecule consists of an iron-hydroxide core chelated in a carbohydrate shell. After dilution and intravenous administration, it is found in the reticuloendothelial system of the liver, spleen and bone marrow and has a terminal half-life of 7–12 hours. Iron is incorporated into red blood cells 6–9 days after injection.

In a trial of 255 patients with chronic kidney disease and iron deficiency anaemia, ferric carboxymaltose given as an intravenous infusion (up to three doses totalling 2000 mg elemental iron over a month) was compared to oral ferrous sulfate (65 mg elemental iron three times a day). The majority of patients were not taking erythropoiesis-stimulating drugs. After eight weeks, more patients receiving ferric carboxymaltose had at least a 1 g/100 mL increase in haemoglobin than those receiving oral iron (60.4% vs 34.7% of patients). This was regardless of whether or not they were receiving erythropoiesisstimulating drugs.¹

Ferric carboxymaltose has also been compared to iron sucrose in patients with chronic kidney disease who were on haemodialysis. All patients were receiving stable doses of an erythropoiesis-stimulating drug. Both treatments were given at a dose of 200 mg iron intravenously two to three times a week. After four weeks, haemoglobin levels had risen by at least 1 g/100 mL in 44.1% (52/118) of patients in the ferric carboxymaltose group and 35.3% (41/116) of those in the iron sucrose group. At the time of writing, this study was not published in full.

Ferric carboxymaltose has also been assessed in other conditions. In a trial of 200 patients with Crohn's disease or ulcerative colitis, treatment with up to three intravenous infusions of ferric carboxymaltose one week apart (up to 1000 mg iron a week) was found to be non-inferior to oral ferrous sulfate (100 mg iron twice a day). After 12 weeks, median haemoglobin concentrations had increased from 8.7 to 12.3 g/100 mL with ferric carboxymaltose and from 9.1 to 12.1 g/100 mL with oral iron.² Ferric carboxymaltose was also effective in treating postpartum iron deficiency.^3-5 In a six-week comparative trial of 291 women with anaemia (haemoglobin ≤10 g/100 mL) after giving birth, 91.4% of women who received ferric carboxymaltose had haemoglobin concentrations greater than 12 g/100 mL. This was compared with 66.7% of women who received oral ferrous sulfate (65 mg iron three times a day).³

Generally, the most common adverse reactions to ferric carboxymaltose were headache, dizziness, nausea, abdominal pain, constipation, diarrhoea, rash and injection site reaction. These were reported by less than 10% of study participants. Decreased blood phosphorus and increased alanine aminotransferase also occurred in some patients. In patients with chronic kidney disease, peripheral oedema (6.1%), hyperkalaemia (4.1%) and urinary tract infection (3.4%) were the most common events.¹ In a safety cohort of 899 patients, there were five deaths. Causes included pulmonary tuberculosis, heart failure, peripartum cardiomyopathy leading to heart failure, myocardial infarction and cardiac arrest.

Transfer into human milk is negligible (≤1%) so breastfeeding is not a contraindication. In a safety analysis of 229 breastfed infants whose mothers were receiving ferric carboxymaltose, adverse reactions included erythema (5 babies), constipation (3 babies), diarrhoea (3 babies), nasopharyngitis (2 babies), pallor and flatulence (2 babies), abdominal pain (1 baby) and upper respiratory tract infection (1 baby).

This drug is contraindicated for anaemia not caused by iron deficiency, or if there is evidence of iron overload or disturbances of iron use. It should also not be used in the first trimester of pregnancy as fetal abnormalites have been observed in preclinical studies, and caution is urged in the second and third trimesters. In patients with hepatic impairment, ferric carboxymaltose should only be used after careful assessment and monitoring.

Anaphylaxis has occurred after intravenous injections of iron preparations so resuscitation facilities should be available during administration of ferric carboxymaltose.

The cumulative dose of ferric carboxymaltose required to restore iron levels should be individually calculated for each patient. As there is a risk of iron overload, patients should have their red cell indices and serum ferritin monitored regularly.

Evidence from the trials suggests that ferric carboxymaltose is an effective alternative for treating iron deficiency when oral iron is not an option. However, it is not clear if it will have advantages over other parenteral iron formulations such as iron sucrose.

manufacturer provided clinical information

The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Note on references

At the time the comment was prepared, information about this drug was available on the website of the Therapeutic Goods Administration (www.tga.gov.au/industry/pm-auspar.htm).