Exjade (Novartis)
125 mg, 250 mg and 500 mg dispersible tablets
Approved indication: iron overload
Australian Medicines Handbook section 4.2

Patients who require frequent transfusions of blood, such as those with thalassaemia, are at risk of chronic accumulation of iron. This excess iron is deposited in the tissues such as the heart and liver resulting in damage and diminished function. To prevent organ failure these patients require the iron to be removed by chelating agents such as desferrioxamine. As desferrioxamine has to be given parenterally, oral chelating agents are being developed. Deferiprone was approved in Australia in 2003.

Deferasirox is another oral chelating agent. After absorption two molecules of deferasirox bind one atom of iron. The complex is then excreted in faeces. Deferasirox is metabolised and has an elimination half-life of 8-16 hours.

A short-term study of 24 adults with thalassaemia found that increasing doses of deferasirox increased iron excretion.1This led to a one-year study of 586 patients with a mean age of 17 years (range 2-53 years). They were randomised to take deferasirox or have subcutaneous desferrioxamine with the doses determined by the concentration of iron found on liver biopsy. (Patients randomised to desferrioxamine could remain on their previous dose.) Depending on the dose, both chelating agents reduced serum concentrations of ferritin. The mean reductions in liver iron concentration, when liver biopsies were repeated at the end of the study, were 2.4 mg/g with deferasirox and 2.9 mg/g with desferrioxamine. Overall 53% of the patients taking deferasirox achieved the target liver iron concentration compared with 66% of the patients given desferrioxamine.

In the main clinical trial serious adverse events such as infections affected approximately 9% of both groups. The most frequent adverse events associated with deferasirox were fever, headache, abdominal pain, nausea, vomiting and diarrhoea. In 11% of patients serum creatinine increased and 19% developed proteinuria. Renal function should therefore be monitored monthly. Monthly liver function tests are also recommended because there is a risk of drug-induced hepatitis. As deferasirox may cause cataracts and reduced hearing, annual eye examinations and hearing tests are advised.

Depending on how the results of the main trial are analysed, the efficacy of deferasirox may be inferior to that of desferrioxamine. In children aged 2-5 years it is only approved for use if desferrioxamine is ineffective or not tolerated.

There does not appear to be a published comparison of deferasirox and deferiprone. Deferasirox only needs to be taken once daily, but it is unknown if it has any other advantages.

Read about The Transparency Score manufacturer provided additional useful information

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

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.