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.

Ferriprox (Orphan)

500 mg tablets
Approved indication: iron overload in thalassaemia
Australian Medicines Handbook section 4.2

Patients with thalassaemia major develop anaemia and require blood transfusions. As the body has a limited capacity to excrete iron, frequent transfusions cause iron overload. This can lead to complications such as cirrhosis, heart failure and diabetes.

To prevent the complications of iron overload patients are treated with desferrioxamine. This is a chelating agent which forms water-soluble complexes in a 1:1 ratio with iron atoms.

These complexes can then be excreted by the kidney. Unfortunately desferrioxamine can only be given by injection and children may require prolonged subcutaneous infusions several times a week. As desferrioxamine is expensive to administer and can have serious adverse effects, there is a need for an oral iron-chelating agent.

Deferiprone is a chelating agent which is rapidly absorbed from the gut. Three molecules of deferiprone will form a complex with one iron atom. This complex is then excreted in the urine. Up to 90% of the dose is excreted within 24hours. Deferiprone is also metabolised, but its metabolite has no chelating activity.

A prospective trial of deferiprone involved 21 patients who were unwilling or unable to take desferrioxamine. During an average of three years of treatment the patients' hepatic iron concentrations fell from a mean of 80.7 to 46.8micromol/g. There was also a significant reduction in serum ferritin.1

Nineteen of the patients in the trial continued treatment. This enabled the researchers to review the efficacy of deferiprone after 4.6 years (mean duration of treatment). They found that the average concentration of hepatic iron had not decreased significantly. In some patients hepatic iron concentrations had increased.2

The researchers also reported that long-term treatment was associated with hepatic fibrosis. This conclusion was controversial and led to lawsuits against the principal researcher.3

While there is an argument about the risk of hepatic fibrosis, there is an association between deferiprone and severe neutropenia and agranulocytosis. The patient's neutrophil count should therefore be monitored weekly. More common adverse events include discolouration of the urine, nausea, vomiting and arthralgia.

While desferrioxamine treatment is inconvenient, compliance with deferiprone is also demanding. To maintain concentrations high enough to form the 3:1 complexes with iron, patients must take a daily dose of deferiprone of 75 mg/kg. This will often equate to several tablets three times a day.

It will take years before we know if deferiprone safely prevents the complications of iron overload. There are no data on the use of the drug in young children. Until there is a good quality study comparing it with desferrioxamine, deferiprone should only be used in patients who cannot tolerate desferrioxamine.